Clinical trial NCT02601313
Conditions: Relapsed/Refractory Mantle Cell Lymphoma
Sponsor: Kite, A Gilead Company
Start date: 2015-11-09; Completion date: 2023-09-22
Enrollment: 105 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL).

Detailed description:
Study KTE-C19-102 enrolled participants with r/r MCL who have been treated with up to 5 prior regimens including a Bruton's tyrosine kinase inhibitor (BTKi) in Cohort 1 and Cohort 2. However, to fulfill FDA Postmarketing Requirement, Cohort 3 is added to the study. It will include participants with r/r MCL who have been treated with up to 5 prior regimens but have not received prior therapy with a BTKi.

The primary analysis in Cohort 1 and Cohort 2 is already completed. Data for Cohort 3 will be analyzed separately. Therefore, details for Cohort 3 were registered separately (NCT04880434) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.

After the end of KTE-C19-102, subjects who received an infusion of anti-CD19 CAR T cells will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Arms: arm 1: Participants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) consisting of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day intravenous (IV) infusion for 3 days followed by a single infusion of axicabtagene ciloleucel at a targeted dose of 2 x 10\^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10\^6 CAR T cells/kg, with a maximum dose of 2 x 10\^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10\^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10\^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.
Interventions: intervention 1: brexucabtagene autoleucel intervention 2: Cyclophosphamide intervention 3: Fludarabine intervention 4: Axicabtagene Ciloleucel
Intervention descriptions: intervention 1: A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells intervention 2: Administered intravenously intervention 3: Administered intravenously intervention 4: A single infusion of axicabtagene ciloleucel anti-CD 19 CAR T cells

Protocol documents:
Prot_002.pdf: 
 
Protocol Title: 
A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects 
with Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2)
Protocol Number: 
KTE-C19-102
IND Number: 
016675
EudraCT Number:
2015-005008-27
Clinical Study Sponsor: 
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Key Sponsor Contact:
The medical monitor name and contact information is provided on the Key Study 
Team Contact List
Version:
Amendment # 9
Date:
07 November 2022
CONFIDENTIALITY STATEMENT
This document contains confidential information of Kite Pharma, Inc., a wholly owned 
subsidiary of Gilead Sciences Inc. This document must not be disclosed to anyone other than the 
study site research staff, collaborators, and members of the Institutional Review 
Board/Independent Ethics Committee, a scientific review board, or an equivalent. The 
information in this document cannot be used for any purpose other than the conduct of the 
clinical investigation without the prior written consent of Kite Pharma, Inc.
.. •.•. Kite 
.. • 
GILE 


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 2
07 Novemeber 2022
SPONSOR AND INVESTIGATOR SIGNATURE PAGE
KITE PHARMA, INC.
2400 BROADWAY
SANTA MONICA, CA 90404
STUDY ACKNOWLEDGMENT
A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects with 
Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2)
Amendment # 9, 07 November 2022
This protocol has been approved by Kite Pharma, Inc. The following signature documents this 
approval.
[See appended electronic signature]
Kite Medical Monitor Name (Printed) 
Signature
[See appended electronic signature]
Date
INVESTIGATOR STATEMENT
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated.
I agree to comply with the International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline on Good Clinical 
Practice and applicable national or regional regulations and guidelines. I will provide all study 
personnel under my supervision copies of the protocol and access to all information provided by 
Kite Pharma, Inc. I will discuss this material with them to ensure that they are fully informed 
about the investigational product and the study.
I agree and will ensure that financial disclosure statements will be completed by:

Me (including, if applicable, my spouse, legal partner and dependent children)

Subinvestigators (including, if applicable, their spouse, legal partner, and dependent children) 
at the start of the study and for up to one year after the study is completed.
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the clinical investigation without prior written consent 
from Kite Pharma, Inc.
Principal Investigator Name (Printed)
Signature
Date
Site Number
PPD
- -- - -


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 3
07 Novemeber 2022
PROTOCOL SYNOPSIS
Title: 
A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects with 
Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2)
Indication:
The treatment of adult subjects with relapsed/refractory mantle cell lymphoma 
(r/r MCL).
Study Design:
Study KTE-C19-102 is a Phase 2, multicenter, open-label study evaluating the efficacy 
of KTE-X19 in subjects with r/r MCL.
Cohort 1 and Cohort 2 will include subjects with r/r MCL who have been treated with 
up to 5 prior regimens including a Bruton’s tyrosine kinase inhibitor (BTKi). Prior 
therapy must have included all of the following: anthracycline- or 
bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and 
ibrutinib or acalabrutinib. Cohort 3 will include subjects with r/r MCL who have been 
treated with up to 5 prior regimens but have not received prior therapy with a BTKi. 
Prior therapy must have included anthracycline-, bendamustine-, or high-dose 
cytarabine-containing chemotherapy and anti-CD20 monoclonal antibody therapy.
Cohort 1 will enroll and treat up to approximately 90 subjects with cyclophosphamide 
and fludarabine conditioning chemotherapy, followed by a target dose of 
2 x 106 anti-CD19 chimeric antigen receptor (CAR) T cells per kg body weight. This 
cohort will include at least 60 but up to approximately 80 subjects treated with 
KTE-X19 (referred to as KTE-X19 subjects in this document) and 10 subjects treated 
with axicabtagene ciloleucel (referred to as axicabtagene ciloleucel subjects in this 
document). The KTE-X19 subjects in this cohort will form the basis for hypothesis 
testing on the primary endpoint in Cohort 1. As of 28 May 2019, Cohort 1 has 
completed enrollment. 
Cohort 2 will enroll and treat up to 40 KTE-X19 subjects with cyclophosphamide and 
fludarabine conditioning chemotherapy, followed by a target dose of 
0.5 x 106 anti-CD19 CAR T cells per kg body weight. As of 01 May 2018, Cohort 2 has 
completed enrollment.
Cohort 3 will enroll and treat up to approximately 90 KTE-X19 subjects with 
cyclophosphamide and fludarabine conditioning chemotherapy, followed by a target 
dose of 2 x 106 anti-CD19 CAR T cells per kg body weight.
Each subject will proceed through the following study periods:

Screening 

Enrollment/Leukapheresis 

Bridging therapy if applicable

Conditioning chemotherapy 

Investigational product (IP) treatment 

Post-treatment assessment 

Long-term follow-up period
For study requirements assigned to each study period, refer to Section 7 for details.    


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 4
07 Novemeber 2022
Study Objectives: 
The primary objective is to evaluate the efficacy of KTE-X19, as measured by objective 
response rate (ORR), in subjects with r/r MCL.  Secondary objectives will include 
assessing the safety and tolerability of KTE-X19 and additional efficacy endpoints 
including duration of response (DOR). 
Secondary objectives related to patient-reported outcomes (PROs) in Cohort 1 and 
Cohort 2 will include change in the European Quality of Life-5 Dimensions (EQ-5D) 
scores from baseline to Month 6. Secondary objectives related to PROs in Cohort 3 will 
include change in EQ-5D and European Organisation for Research and Treatment of 
Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) scores from baseline over 
time.
Hypothesis:
This study uses an open-label 3-cohort design.  
Among the Cohort 1 KTE-X19 subjects, with a target 50% response rate per 
independent review, an alternative hypothesis will be tested against a null hypothesis 
that the response rate is 25% or less.  The hypothesis is that the ORR to KTE-X19 per 
independent review is significantly greater than 25% in Cohort 1 KTE-X19 subjects.
Among the Cohort 3 subjects, with a target 75% ORR per independent review, an 
alternative hypothesis will be tested against a null hypothesis that the ORR is 57% or 
less. The hypothesis is that the ORR to KTE-X19 per independent review is 
significantly greater than 57% in Cohort 3 subjects.
No hypothesis will be tested in Cohort 1 axicabtagene ciloleucel subjects and Cohort 2 
KTE-X19 subjects. 
 
Primary Endpoint:
ORR (complete response [CR] + partial response [PR]) per the Lugano Classification 
{Cheson 2014} per Independent Radiology Review Committee (IRRC) review
Secondary 
Endpoints:

DOR

Best objective response (BOR)

ORR as determined by study investigators

Progression-free survival

Overall survival 

Incidence of adverse events (AEs) and clinically significant changes in laboratory 
values

Incidence of anti-CD19 CAR antibodies

Levels of anti-CD19 CAR T cells in blood

Levels of cytokines in serum

Changes over time in the EQ-5D scale score and visual analogue scale score

Changes over time in the EORTC-QLQ-C30 score (Cohort 3 only)
Exploratory 
Endpoints:
CCI
CCI
-


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 5
07 Novemeber 2022
Sample Size: 

Up to approximately 220 subjects will be enrolled and treated in the study: 

90 subjects in Cohort 1 (10 axicabtagene ciloleucel subjects and approximately 
80 KTE-X19 subjects) at 2 x 106 anti‑CD19 CAR T cells per kg body weight 

Up to 40 KTE-X19 subjects in Cohort 2 at 0.5 x 106 anti‑CD19 CAR T cells 
per kg body weight

Up to approximately 90 KTE-X19 subjects in Cohort 3 at 2 x 106 anti-CD19 
CAR T cells per kg body weight
Study Eligibility:
Refer to Section 5 for a detailed list of inclusion and exclusion criteria.
Treatment:
Bridging Therapy:

Cohort 1 and Cohort 2:

At the discretion of the investigator and after discussion with the medical 
monitor, bridging therapy may be considered for any subject, particularly those 
with high disease burden at screening (eg, > 25% marrow involvement and/or 
≥ 1,000 leukemic phase mantle cells/mm3 in the peripheral circulation).

Bridging therapy is allowed with (1) dexamethasone or other corticosteroid, 
(2) ibrutinib, or (3) acalabrutinib.

If prescribed, bridging therapy must be administered after leukapheresis and 
completed at least 5 days prior to initiating conditioning chemotherapy. 

Cohort 3:

At the discretion of the investigator and per institutional guidelines and 
standard of care and after discussion with the medical monitor, bridging 
therapy is recommended for all subjects, particularly those with rapidly 
progressing disease, clinical deterioration, or high disease burden at screening 
(eg, > 25% marrow involvement and/or ≥ 1,000 leukemic phase mantle 
cells/mm3 in the peripheral circulation).

Bridging therapy is allowed with (1) dexamethasone or other corticosteroid, 
(2) palliative radiotherapy to localized lesions, (3) specified chemotherapy, or 
(4) any combination of 1 specified chemotherapy and/or corticosteroid and/or 
radiotherapy, as detailed in Section 6.2.1.2. Bridging regimen should be 
discussed with the Kite medical monitor, and BTKis are not permitted for 
bridging therapy. If radiotherapy is considered for bridging, the radiotherapy 
modality should be discussed with the Kite medical monitor. Irradiated lesions 
can no longer serve as target lesions, and other target lesions must be present 
to allow for response assessment.

If prescribed, bridging therapy must be administered after leukapheresis and 
completed at least 7 days or 5 half-lives, whichever is shorter, prior to 
initiating conditioning chemotherapy. 

Refer to Section 6 for dosing and further details.
Conditioning Chemotherapy Treatment:

KTE-X19 or axicabtagene ciloleucel is administered after a conditioning 
chemotherapy regimen consisting of fludarabine 30 mg/m2/day and 
cyclophosphamide 500 mg/m2/day, administered x 3 days.  Refer to Section 6 for 
chemotherapy treatment details.


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 6
07 Novemeber 2022
IP:

KTE-X19 or axicabtagene ciloleucel treatment consists of a single infusion of 
CAR-transduced autologous T cells administered intravenously at a target dose of 
2 x 106 anti-CD19 CAR T cells/kg (Cohort 1 and Cohort 3) or 0.5 x 106 anti-CD19 
CAR T cells/kg (Cohort 2). In Cohort 3, under circumstances where subjects 
initially respond and subsequently relapse, subjects may be eligible for a second 
course of conditioning chemotherapy and KTE-X19. Refer to Section 6 for 
treatment details and Section 7.12.10 for retreatment details.
Procedures:
At specific time points as outlined in the schedule of assessments, subjects will undergo 
the following assessments/procedures:  collection of informed consent; demographic 
data; general medical history, including previous treatments for MCL and disease 
staging at study entry (per the Lugano Classification {Cheson 2014} for subjects in 
Cohort 3); physical exam, including vital signs and performance status; neurological 
assessments; blood draws for complete blood count (CBC), chemistry panels, 
cytokines, C-reactive protein, ferritin, lactate dehydrogenase, lymphocyte subsets, 
anti-CD19 CAR antibodies, replication-competent retrovirus (RCR), and anti-CD19 
CAR T cells analysis; and bone marrow aspirate or biopsy and blood draws for minimal 
residual disease (MRD) analysis. Females of childbearing potential will undergo a urine 
or serum pregnancy test. 
Subjects will also undergo a baseline electrocardiogram (ECG), echocardiogram 
(ECHO) (or multigated acquisition [MUGA] scan for subjects in Cohort 3), brain 
magnetic resonance image (MRI) (or computed tomography [CT] scan with contrast for 
subjects in Cohort 3 with a contraindication for MRI), a positron emission 
tomography-computed tomography (PET-CT), bone marrow aspirate or biopsy, and 
leukapheresis. 
Routinely throughout the conduct of the study, subjects will be asked to complete the 
EQ-5D questionnaire, EORTC-QLQ-C30 (Cohort 3 only), report concomitant therapies 
and AEs, and will have their disease assessed.
Data Safety 
Monitoring Board:
An independent Data Safety Monitoring Board (DSMB) will review safety and/or 
efficacy data from Cohort 1 and Cohort 2 at 4 times during this study.  The DSMB will 
first meet to review safety data when 10 subjects in Cohort 1 have been enrolled and 
treated with anti-CD19 CAR T cells and followed for 30 days.  The DSMB will meet 
for the second time to review both safety and efficacy data after 20 subjects in Cohort 1 
have been enrolled, treated, and have had the opportunity to complete the 3-month 
disease assessment.  The DSMB will meet for the third time to review both safety and 
efficacy data after 10 subjects in Cohort 2 have been enrolled, treated, and have had the 
opportunity to be followed for 30 days. The DSMB will meet for the fourth time to 
review safety data after 44 subjects in Cohort 1 have been enrolled, treated, and have 
had the opportunity to be followed for at least 30 days, with focus on the safety data 
from the 6 KTE-X19 subjects treated most recently in this cohort. The DSMB will be 
chartered to make trial conduct recommendations for Cohort 1 and Cohort 2 based on 
an analysis of risk vs benefit.  The DSMB may meet more often as needed.  Refer to 
Section 9.10 and Section 9.12.
Scientific Steering 
Committee 
(Cohort 3):
A scientific steering committee, comprising the study sponsor and at least 3 study 
investigators, will be specifically chartered to review the safety data from Cohort 3 and 
make recommendations on further study conduct. The scientific steering committee will 
meet after 15 subjects in Cohort 3 have been enrolled and treated with KTE-X19 and 
have had the opportunity to be followed for 30 days, and again after 50 subjects in 
Cohort 3 have been enrolled and treated with KTE-X19 and have had the opportunity to 
be followed for 3 months. The scientific steering committee may meet more often as 
needed. Refer to Section 9.11 and Section 9.12.


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 7
07 Novemeber 2022
Statistical 
Considerations:
This study uses an open-label, 3-cohort design. 
Among the Cohort 1 KTE-X19 subjects, with a target 50% response rate per 
independent review, an alternative hypothesis will be tested against a null hypothesis 
that the response rate is 25% or less.  For the test of efficacy in the Cohort 1 KTE-X19 
subjects, this study has at least 96% power to distinguish between an active therapy 
with a 50% true response rate from a therapy with a response rate of 25% or less with a 
1-sided alpha level of 0.025. 
Among the Cohort 3 subjects, with a target 75% ORR per independent review, an 
alternative hypothesis will be tested against a null hypothesis that the ORR is 57% or 
less. For the test of efficacy in Cohort 3, this study has at least 90% power to 
distinguish between an active therapy with a 75% true response rate and a therapy with 
a response rate of 57% or less with a 1-sided alpha level of 0.025.
No hypothesis will be tested on Cohort 1 axicabtagene ciloleucel subjects or Cohort 2 
subjects.
Four interim analyses will be performed in Cohort 1, 1 interim analysis will be 
performed in Cohort 2, and 2 interim analyses (for safety only) will be performed in 
Cohort 3. The primary analysis in Cohort 1 will be performed after 60 Cohort 1 
KTE-X19 subjects have been enrolled and treated and have had the opportunity to be 
assessed for response 6 months after the Week 4 disease assessment. The primary 
analysis in Cohort 3 will be conducted after 86 subjects in Cohort 3 have been enrolled 
and treated with KTE-X19 and have had the opportunity to be assessed for response 
6 months after the first objective response or 9 months after the KTE-X19 infusion, 
whichever is earlier.

Cohort 1 interim analysis 1 will be conducted after 10 subjects in Cohort 1 have 
been enrolled and treated with anti-CD19 CAR T cells and followed for 30 days.  
This interim analysis will be for safety only. 

Cohort 1 interim analysis 2 will be conducted after 20 subjects in Cohort 1 
(Section 10.5) have been enrolled and treated with anti-CD19 CAR T cells and 
have had the opportunity to be evaluated for response 3 months after the IP 
infusion. This interim analysis will be for safety and efficacy (futility only).

Cohort 1 interim analysis 3 will occur after 38 subjects treated with anti-CD19 
CAR T cells in Cohort 1 have had the opportunity to be assessed for response 
6 months after the IP infusion.

Cohort 1 interim analysis 4 will be conducted after 44 subjects in Cohort 1 have 
been enrolled and treated with anti-CD19 CAR T cells and have had the 
opportunity to be followed for at least 30 days after the IP infusion.  This interim 
analysis will assess safety only, with focus on the KTE-X19 subjects treated most 
recently in this cohort.  

Cohort 2 interim analysis will be conducted after 10 subjects in Cohort 2 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed 
for 30 days after the KTE-X19 infusion.  This interim analysis will assess safety 
and efficacy.  

Cohort 3 interim analysis 1 will be conducted after 15 subjects in Cohort 3 have 
been enrolled and treated with KTE-X19 and have had the opportunity to be 
followed for 30 days after the KTE-X19 infusion. This interim analysis will be for 
safety only. 

Cohort 3 interim analysis 2 will be conducted after 50 subjects in Cohort 3 have 
been enrolled and treated with KTE-X19 and have had the opportunity to be 
followed for 3 months after the KTE-X19 infusion. This interim analysis will be 
for safety only.


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 8
07 Novemeber 2022
The primary analysis in Cohort 1 will occur after 60 KTE-X19 subjects in the modified 
intent-to-treat (mITT) set of Cohort 1 have been enrolled and treated with KTE-X19 
and have had the opportunity to be assessed for response 6 months after the Week 4 
disease assessment.
The primary analysis in Cohort 3 will occur after 86 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be assessed for 
response 6 months after the first objective response or 9 months after the KTE-X19 
infusion, whichever is earlier. A follow-up analysis will be performed after 86 subjects 
in Cohort 3 have had the opportunity to be assessed for response 18 months after the 
first objective response to further evaluate the risk-benefit profile of KTE-X19, 
including the durability of response.


KTE-C 19-102 
Clinical Protocol 
Kite Pha1ma, Inc. 
Figure 1. 
Study Schema 
,..-._ 
Conditioning Chemotherapy 
Investigational Product (IP} 
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A,., 
Study KTE-Cl9-102 is a Phase 2, multicenter, open-label study evaluating the efficacy ofKTE-X19 in subjects with relapsed/refracto1y mantle cell 
lymphoma (r/r MCL). 
Up to approximately 220 subjects with r/r MCL will be enrolled and treated in 3 separate cohorts designated as Coho1t 1, Coho1t 2, and Coho1t 3. 
Cohort 1 and Coho1t 2 will include subjects with r/r MCL who have been treated with up to 5 prior regimens including a Bmton's tyrosine kinase 
inhibitor (BTKi). 
• 
Cohort 1 will enroll and treat 90 subjects at a target dose of 2 x 106 anti-CD 19 CAR T cells/kg, including 10 axicabtagene ciloleucel subjects and 
approximately 80 KTE-X19 subjects. 
• 
Cohort 2 will enroll and treat up to approximately 40 KTE-Xl9 subjects at a target dose of0.5 x 106 anti-CD19 CART cells/kg. 
Cohort 3 will include subjects with r/r MCL who have been treated with up to 5 prior regimens but have not received prior therapy with a BTKi. 
• 
Cohort 3 will enroll and treat up to approximately 90 KTE-X19 subjects at a target dose of2 x 106 anti-CD19 CART cells/kg. 
Note: After the end ofKTE-C19-102, subjects who received an infusion of anti-CD19 CART cells will complete the remainder of the 15-year 
follow-up assessments in a separate long-tenn follow-up study, KT-US-982-5968. 
Final 
CONFIDENTIAL 
Page9 
07 November 2022 


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 10
07 November 2022
TABLE OF CONTENTS
SPONSOR AND INVESTIGATOR SIGNATURE PAGE............................................................................................2
PROTOCOL SYNOPSIS................................................................................................................................................3
TABLE OF CONTENTS..............................................................................................................................................10
LIST OF TABLES........................................................................................................................................................13
LIST OF FIGURES ......................................................................................................................................................13
LIST OF ABBREVIATIONS.......................................................................................................................................14
1.
OBJECTIVES.......................................................................................................................................................17
2.
DISEASE BACKGROUND AND RATIONALE...............................................................................................18
2.1.
First-line Therapy ....................................................................................................................................18
2.2.
Therapy for R/R MCL.............................................................................................................................19
2.2.1.
Rationale for Cohort 3...........................................................................................................22
2.3.
Novel T-cell Immunotherapies................................................................................................................24
2.4.
CD19 and Expression..............................................................................................................................25
2.5.
Anti-CD19 CAR T-cell Product..............................................................................................................25
2.5.1.
Axicabtagene Ciloleucel........................................................................................................26
2.5.2.
KTE-X19 ...............................................................................................................................26
2.6.
Prior Experience with KTE-X19 and Other Anti-CD19 CAR T Cells ...................................................26
2.7.
KTE-X19 .................................................................................................................................................26
3.
STUDY DESIGN.................................................................................................................................................27
3.1.
General Study Design..............................................................................................................................27
3.2.
Participating Sites....................................................................................................................................28
3.3.
Number of Subjects .................................................................................................................................29
3.4.
Replacement of Subjects .........................................................................................................................29
3.5.
Study Duration.........................................................................................................................................29
3.5.1.
Study Duration for Individual Subjects.................................................................................29
3.5.2.
Completion of Study..............................................................................................................29
3.5.3.
LTFU .....................................................................................................................................29
4.
SUBJECT SCREENING AND ENROLLMENT................................................................................................31
5.
SUBJECT ELIGIBILITY.....................................................................................................................................32
5.1.
Inclusion Criteria.....................................................................................................................................32
5.2.
Exclusion Criteria....................................................................................................................................33
6.
PROTOCOL TREATMENT................................................................................................................................36
6.1.
Treatment Terminology...........................................................................................................................36
6.2.
Study Treatment ......................................................................................................................................36
6.2.1.
Bridging Therapy...................................................................................................................36
6.2.2.
Conditioning Chemotherapy .................................................................................................38
6.2.3.
KTE-X19 ...............................................................................................................................39
6.2.4.
Concomitant Therapy ............................................................................................................40
6.2.5.
Excluded Medications ...........................................................................................................41
6.2.6.
Subsequent Therapy ..............................................................................................................41
6.3.
Study Treatment Schedule.......................................................................................................................41
6.3.1.
Leukapheresis (Within Approximately 5 Days of Eligibility 
Confirmation)........................................................................................................................41
6.3.2.
Bridging Therapy...................................................................................................................42


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 11
07 November 2022
6.3.3.
Cyclophosphamide and Fludarabine (Days –5 Through –3 Before 
Infusion of anti-CD19 CAR T cells).....................................................................................43
6.3.4.
KTE-X19 or axicabtagene ciloleucel (Day 0, after Fludarabine and 
Cyclophosphamide)...............................................................................................................44
6.4.
Toxicity Management..............................................................................................................................44
7.
STUDY PROCEDURES......................................................................................................................................46
7.1.
Informed Consent ....................................................................................................................................46
7.2.
Demographic Data...................................................................................................................................46
7.3.
Medical and Treatment History...............................................................................................................46
7.4.
Physical Exam, Vital Signs, Performance Status, and PROs..................................................................47
7.4.1.
PROs......................................................................................................................................47
7.5.
Neurological Assessment ........................................................................................................................48
7.5.1.
Cohort 1 and Cohort 2 ...........................................................................................................48
7.5.2.
Cohort 3.................................................................................................................................48
7.6.
Bone Marrow Assessment.......................................................................................................................49
7.7.
Lumbar Puncture .....................................................................................................................................50
7.8.
Disease Response Assessment ................................................................................................................51
7.9.
Cardiac Function .....................................................................................................................................52
7.10.
Brain MRI................................................................................................................................................52
7.11.
Laboratory ...............................................................................................................................................52
7.11.1.
Biomarkers ............................................................................................................................54
7.12.
Description of Study Periods...................................................................................................................56
7.12.1.
Screening ...............................................................................................................................56
7.12.2.
Rescreening ...........................................................................................................................58
7.12.3.
Enrollment/Leukapheresis.....................................................................................................58
7.12.4.
Bridging Therapy...................................................................................................................60
7.12.5.
Conditioning Chemotherapy Period......................................................................................60
7.12.6.
IP Treatment Period...............................................................................................................62
7.12.7.
Requirements to Work Up Potential Infectious and/or Inflammatory 
States .....................................................................................................................................65
7.12.8.
Post-treatment Assessment Period ........................................................................................66
7.12.9.
LTFU Period..........................................................................................................................68
7.12.10.
Retreatment............................................................................................................................71
7.13.
SOAs........................................................................................................................................................75
8.
SUBJECT WITHDRAWAL ................................................................................................................................87
8.1.
Reasons for Removal from Treatment ....................................................................................................88
8.2.
Reasons for Removal from Study............................................................................................................88
9.
SAFETY REPORTING........................................................................................................................................89
9.1.
AEs ..........................................................................................................................................................89
9.2.
Reporting of AEs.....................................................................................................................................89
9.2.1.
Grading of CRS and Neurologic Events ...............................................................................90
9.3.
Definition of SAEs ..................................................................................................................................91
9.4.
Reporting of SAEs and Non-serious CRS Events Grade ≥ 3..................................................................91
9.5.
Reporting Deaths.....................................................................................................................................92
9.6.
Diagnosis Versus Signs and Symptoms ..................................................................................................93
9.7.
Pregnancy and Lactation .........................................................................................................................93
9.8.
Hospitalization and Prolonged Hospitalization.......................................................................................94
9.9.
Abnormal Vital Signs Values..................................................................................................................94
9.10.
DSMB......................................................................................................................................................94
9.10.1.
Cohort 1 and Cohort 2 ...........................................................................................................94
9.10.2.
All Cohorts ............................................................................................................................95
9.11.
Scientific Steering Committee (Cohort 3)...............................................................................................95


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9.12.
Criteria to Pause Enrollment ...................................................................................................................95
10.
STATISTICAL CONSIDERATIONS.................................................................................................................97
10.1.
Hypothesis ...............................................................................................................................................97
10.2.
Study Endpoints.......................................................................................................................................97
10.2.1.
Primary ..................................................................................................................................97
10.2.2.
Secondary ..............................................................................................................................97
10.2.3.
Exploratory Endpoints...........................................................................................................98
10.3.
Sample Size Considerations ....................................................................................................................98
10.4.
Statistical Assumptions .........................................................................................................................100
10.5.
Analysis Subsets....................................................................................................................................100
10.6.
Access to Individual Subject Treatment Assignments ..........................................................................100
10.7.
Interim Analysis ....................................................................................................................................101
10.7.1.
Interim Analysis and Early Stopping Rules ........................................................................101
10.7.2.
Safety Interim Analysis .......................................................................................................101
10.7.3.
Efficacy Interim Analysis....................................................................................................102
10.7.4.
Other Interim Analysis ........................................................................................................102
10.8.
Planned Methods of Analysis................................................................................................................102
10.8.1.
Primary and Additional Analyses........................................................................................102
10.8.2.
ORR.....................................................................................................................................103
10.8.3.
Best Objective Response .....................................................................................................103
10.8.4.
DOR.....................................................................................................................................103
10.8.5.
PFS ......................................................................................................................................104
10.8.6.
OS........................................................................................................................................104
10.8.7.
Safety...................................................................................................................................104
10.8.8.
Long-term Data Analysis ....................................................................................................104
11.
REGULATORY OBLIGATIONS.....................................................................................................................105
11.1.
Independent Review Board/Independent Ethics Committee.................................................................105
11.2.
Subject Confidentiality..........................................................................................................................105
11.3.
Investigator Signatory Obligations........................................................................................................106
11.4.
Ethics .....................................................................................................................................................106
12.
PROTOCOL AMENDMENTS AND TERMINATION ...................................................................................107
13.
STUDY DOCUMENTATION AND ARCHIVE ..............................................................................................108
14.
STUDY MONITORING AND DATA COLLECTION....................................................................................110
15.
PUBLICATION .................................................................................................................................................111
16.
COMPENSATION.............................................................................................................................................112
17.
REFERENCES...................................................................................................................................................113
18.
APPENDIX ........................................................................................................................................................125
18.1.
Appendix 1:  Revised International Working Group Response Criteria for Malignant 
Lymphoma.............................................................................................................................................125
18.1.1.
Complete Response .............................................................................................................125
18.1.2.
Partial Response ..................................................................................................................125
18.1.3.
Stable Disease......................................................................................................................126
18.1.4.
Progressive Disease.............................................................................................................126
18.2.
Appendix 2:  Lugano Classification......................................................................................................127
18.2.1.
Disease Staging ...................................................................................................................127
18.2.2.
Disease Response Assessment ............................................................................................127
18.3.
Appendix 3:  Monitoring of Subjects After IP Administration per Country Regulatory 
Agencies ................................................................................................................................................131
18.4.
Appendix 4: Cytokine Release Syndrome Grading per Lee, 2014 .......................................................132


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18.5.
Appendix 5: Cytokine Release Syndrome Grading per American Society for Transplantation 
and Cellular Therapy .............................................................................................................................133
18.6.
Appendix 6: Neurologic Event Grading per American Society for Transplantation and 
Cellular Therapy....................................................................................................................................134
18.7.
Appendix 7: Childbearing Potential and Birth Control.........................................................................136
18.7.1.
Definition of Childbearing Potential ...................................................................................136
18.7.2.
Birth Control Methods That May Be Considered as Highly Effective ...............................136
18.7.3.
Unacceptable Birth Control Methods..................................................................................137
LIST OF TABLES
Table 1.
Treatment Outcomes in First-line MCL ..................................................................................19
Table 2.
Outcomes with Available Therapies in r/r MCL.....................................................................21
Table 3.
Treatment Outcomes in r/r MCL After Progressing on Ibrutinib............................................21
Table 4.
Studies Included in the Meta-analysis to Determine Historical Control ORR........................23
Table 5.
Bridging Therapy for Cohort 3................................................................................................38
Table 6.
Bridging Therapy for Cohort 3 Retreatment ...........................................................................74
Table 7.
Schedule of Assessments Cohorts 1 & 2 (1 of 2)....................................................................75
Table 8.
Schedule of Assessments Cohorts 1 & 2 (2 of 2)....................................................................78
Table 9. 
Schedule of Assessments Cohort 3 (1 of 2).............................................................................80
Table 10.
Schedule of Assessments Cohort 3 (2 of 2).............................................................................84
Table 11.
Disease Staging System per Cheson, 2014............................................................................127
Table 12.
5-point Scale (5PS)................................................................................................................127
Table 13.
CRS Grading Scale (Excluding Neurologic Events) per Lee, 2014......................................132
Table 14.
Definitions of High-dose Vasopressors in Adults .................................................................132
Table 15.
ASTCT CRS Consensus Grading..........................................................................................133
Table 16.
ASTCT ICANS Consensus Grading for Adults....................................................................134
Table 17.
Immune Effector Cell-associated Encephalopathy Scorea ....................................................135
LIST OF FIGURES
Figure 1.
Study Schema ............................................................................................................................9
Figure 2.
Anti-CD19 CAR......................................................................................................................25
Figure 3.
Bone Marrow Assessment Schema .........................................................................................50


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LIST OF ABBREVIATIONS
AE
Adverse event
alloSCT
Allogeneic stem cell transplant
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
AST
Aspartate aminotransferase
ASTCT
American Society for Transplantation and Cellular Therapy
AUC0-28
Area under curve from Day 0 to Day 28
autoSCT
Autologous stem cell transplant
BR
Bendamustine and rituximab
BTKi
Bruton’s tyrosine kinase inhibitor
CAR
Chimeric antigen receptor 
CBC
Complete blood count
CLL
Chronic lymphocytic leukemia
CNS
Central nervous system
CPF
Cell processing facility
CR
Complete response
CRF
Case report form
CRO
Contract Research Organization
CRP
C-reactive protein
CRS
Cytokine release syndrome
CSF
Cerebrospinal fluid
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DOR
Duration of response
DSMB
Data Safety Monitoring Board
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG
Eastern Cooperative Oncology Group
EORTC-QLQ-C30
European Organisation for Research and Treatment of Cancer Quality of Life 
Questionnaire
EU
European Union
EQ-5D
European Quality of Life-5 Dimensions
FFPE
Formalin-fixed paraffin-embedded
GCP
Good Clinical Practice
GOT
Glutamic-oxaloacetic transaminase
GPT
Glutamic-pyruvic transaminase
GVHD
Graft-versus-host-disease
HEENT
Head, ears, eyes, nose, and throat
HIV
Human immunodeficiency virus


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HLH
Hemophagocytic lymphohistiocytosis
HRQoL
Health-related quality of life
IB
Investigator’s Brochure
ICANS
Immune effector cell-associated neurotoxicity syndrome
ICE
Immune effector cell-associated encephalopathy
ICF
Informed consent form
ICH
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use
ID
Identification
Ig
Immunoglobulin
IND
Investigational new drug
IP
Investigational product
IRB/IEC
Institutional Review Board/Independent Ethics Committee
IRRC
Independent Radiology Review Committee 
IV
Intravenous
IWG
International Working Group 
LDH
Lactate dehydrogenase
LTFU
Long-term follow-up
LVEF
Left ventricular ejection fraction
MCL
Mantle cell lymphoma
mITT
Modified intent-to-treat
MMSE
Mini-Mental Status Exam
MRD
Minimal residual disease
MRI
Magnetic resonance imaging
MUGA
Multigated acquisition
NCI
National Cancer Institute
NHL
Non-Hodgkin lymphoma
ORR
Objective response rate
OS
Overall survival
PBMC
Peripheral blood mononuclear cell
PCR
Polymerase chain reaction
PD
Progressive disease
PET-CT
Positron emission tomography-computed tomography
PFS
Progression-free survival
PO
Orally
PR
Partial response
PRO
Patient-reported outcome
QoL
Quality of life
qPCR
Quantitative polymerase chain reaction
R-BAC
Rituximab with bendamustine and cytarabine
R-CHOP
Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone


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R-DHAP
Rituximab with dexamethasone, high-dose cytarabine, and cisplatin
RCR 
Replication-competent retrovirus
r/r
Relapsed/refractory
SAE
Serious adverse event
SCT
Stem cell transplant
SD
Stable disease
SOA
Schedule of assessments
SUSAR
Suspected unexpected serious adverse reaction 
TEAE
Treatment-emergent adverse event
US
United States
VAS
Visual analogue scale
WBC
White blood cell


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1.
OBJECTIVES
The primary objective is to evaluate the efficacy of KTE-X19, as measured by objective 
response rate (ORR), in subjects with relapsed/refractory (r/r) mantle cell lymphoma (MCL).  
Secondary objectives will include assessing the safety and tolerability of KTE-X19 and 
additional efficacy endpoints including duration of response (DOR). 
Secondary objectives related to patient-reported outcomes (PROs) in Cohort 1 and Cohort 2 will 
include change in the European Quality of Life-5 Dimensions (EQ-5D) scores from baseline to 
Month 6. Secondary objectives related to PROs in Cohort 3 will include change in EQ-5D and 
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 
(EORTC-QLQ-C30) scores from baseline over time.


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2.
DISEASE BACKGROUND AND RATIONALE
MCL is an aggressive, generally incurable, B-cell malignancy, representing approximately 6% of 
non-Hodgkin lymphomas (NHLs).  Approximately 4000 new cases are diagnosed yearly in the 
United States (US) {Leukemia & Lymphoma Society 2014}.  The lymphoma cells are thought to 
originate from naïve pregerminal center B cells within the mantle zone, and they typically 
express CD5, CD19, CD20, surface immunoglobulin (Ig)M, and surface IgD {Dreyling 2014a} 
but not CD11c {Kraus 2010}.  More than 95% of MCLs carry translocation t(11;14)(q13;q32), 
which places the cyclin D1 gene in proximity of the Ig heavy chain locus, resulting in 
overexpression of cyclin D1, which can be detected by cytogenetics or fluorescence in situ 
hybridization {National Comprehensive Cancer Network 2017}.  Most patients are male, and the 
median age of diagnosis is 68 years {Fakhri 2017}.  Patients typically present with advanced 
lymphadenopathy, and also show extranodal involvement of the spleen, bone marrow, and 
gastrointestinal (GI) tract {Dreyling 2014b, National Comprehensive Cancer Network 2017, 
Rajabi 2015, Vose 2017}.  Prognosis varies based on clinical and laboratory parameters and can 
be estimated using the mantle cell international prognostic index.  This index uses the 
4 independent prognostic factors of age, performance status, lactate dehydrogenase (LDH), and 
leukocyte count to classify patients as low risk (60% to 83% 5-year overall survival [OS]), 
intermediate (35% to 63% 5-year OS), or high risk (20% to 34% 5-year OS) {Hoster 2008, 
Hoster 2014}.  
2.1.
First-line Therapy
Most patients require systemic therapy at the time of diagnosis.  First-line therapy for MCL 
typically includes chemotherapy in combination with a CD20 targeting antibody (Table 1) 
{Dreyling 2017, National Comprehensive Cancer Network (NCCN) 2020}.  Common 
combination regimens include rituximab with cyclophosphamide, doxorubicin, vincristine, and 
prednisone (R-CHOP); rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP); 
and bendamustine and rituximab (BR) {Flinn 2014, Kluin-Nelemans 2012, Lenz 2005}.  
Treatment intensification for younger patients combines aggressive chemotherapy regimens with 
autologous stem cell transplant (autoSCT). Regimens such as rituximab with dexamethasone, 
high-dose cytarabine, and cisplatin (R-DHAP) alternating with R-CHOP (R-CHOP/R-DHAP) 
{Hermine 2016}, rituximab in combination with fractionated cyclophosphamide, vincristine, 
doxorubicin and dexamethasone (hyper-CVAD) alternating with high-dose methotrexate and 
cytarabine (MA) (R-HyperCVAD/MA) {Romaguera 2005, Romaguera 2010}, or high-dose 
chemotherapy followed by autoSCT in first remission with or without maintenance rituximab 
{Dreyling 2005, Le Gouill 2016} have led to improved outcomes at the expense of additional 
toxicity. For patients who are unfit for intensive chemotherapy or are not candidates for 
autoSCT, less aggressive regimens are given, such as BR, R-CHOP with or without maintenance 
rituximab, or rituximab with bendamustine and cytarabine (R-BAC) {Dreyling 2017, National 
Comprehensive Cancer Network (NCCN) 2020, Visco 2013}.  Despite high initial response rates 
to these therapies, almost all patients eventually develop progressive disease (PD). 


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Table 1.
Treatment Outcomes in First-line MCL
Regimen
N
Outcome
Reference
R-CHOP v CHOP
122
ORR 94 v 75%; CR 34 v 7%, 
mTTF = 21 v 14 m
{Lenz 2005}
R-CHOP v R-FC
560
ORR 86 v 78%; CR 34 v 40%; 
4 yr OS 62 v 47%
{Kluin-Nelemans 
2012}
BR v R-CHOP/R-CVP
74
ORR 94 v 85%; CR 50 v 27%
{Flinn 2014} 
R-CHOP/R-DHAP v R-CHOP
497
ORR 94 v 90%; CRa 55 v 39%
{Hermine 2016}
R-HyperCAD/MA
97
CR 77%, mTTF= 4.6 yr
{Romaguera 2005}
{Romaguera 2010}
ASCT v IFN-α in first remission
122
mPFS 39 v 17m; 2 yr OS 86 v 
82%
{Dreyling 2005} 
RM v no RM after R-DHAP plus ASCT
290
4 yr EFS 79 v 61%; 4 yr PFS 82 v 
65%; 4 yr OS 89 v 81%
{Le Gouill 2016}
R-BAC
20b
ORR 100%; CR 95%; 
2 yr PFS 95%
{Visco 2013}
Abbreviations:  ASCT, autologous stem cell transplant; BR, bendamustine + rituximab; CHOP, cyclophosphamide + doxorubicin 
+ vincristine + prednisone; CR, complete response; EFS, event-free survival; IFN-α, interferon-alpha; m, month; MA, 
methotrexate + cytarabine; MCL, mantle cell lymphoma; mPFS, median progression-free survival; mTTF, median time-to-
treatment failure; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; R-BAC, rituximab + 
bendamustine + cytarabine; R-CHOP, rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone; R-CVP, 
rituximab + cyclophosphamide + vincristine + prednisone; R-DHAP, rituximab + dexamethasone + high-dose cytarabine + 
cisplatin; R-FC, rituximab + fludarabine + cyclophosphamide; R-HyperCAD, rituximab + fractionated cyclophosphamide + 
vincristine + doxorubicin + dexamethasone; RM, rituximab maintenance; yr, year.
a
CR rates include unconfirmed CR.
b
Data based on previously untreated subjects.
2.2.
Therapy for R/R MCL
There is no established paradigm for the treatment of r/r MCL.  Treatment options includes 
cytotoxic chemotherapy, proteasome inhibitors, immunomodulatory drugs, tyrosine kinase 
inhibitors, and stem cell transplant (SCT).  The choice of regimen is influenced by prior therapy, 
comorbidities, and tumor chemosensitivity.  
Cytotoxic chemotherapy combination regimens used in r/r MCL include R-BAC {Visco 2013} 
and fludarabine/cyclophosphamide (FC), although this regimen is less efficacious in the relapsed 
setting than as a first-line treatment and is associated with substantial toxicities {Cohen 2001}.  
For patients with poorer fitness, less intensive therapies are considered based on first-line 
treatment data, including rituximab alone, chlorambucil, cladribine, or thalidomide, usually in 
combination with rituximab, but these single cytotoxic agent-based regimens have limited 
efficacy compared to multi-agent approaches {Foran 2000, Inwards 2008, Kaufmann 2004, 
Sachanas 2011}.  
SCT has a role in r/r MCL, although its use is limited to those patients who are younger and have 
good fitness.  AutoSCT is more commonly used than allogeneic, and, in eligible patients, results 
in approximately 25% to 35% event-free survival after 2 to 3 years of follow-up {Ketterer 1997, 


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Vose 2000}.  Allogeneic stem cell transplant (alloSCT) has been investigated in multiple single 
institution and registry studies in relapsed and refractory disease, including patients who have 
previously undergone autoSCT.  Results from these studies are variable, likely in part due to 
selection bias in single institution and registry based studies, but suggest approximately 25% of 
patients undergoing alloSCT achieve durable remissions if their disease is demonstrated to be 
chemosensitive prior to transplant {Rajabi 2015}.  However, in these studies, alloSCT has been 
associated with high morbidity and non-relapse mortality, mostly due to graft-versus-host disease 
(GVHD) and its complications and affecting 30% to 40% of patients.
Targeted therapies such as bortezomib, lenalidomide, ibrutinib, acalabrutinib, and zanubrutinib 
have been approved in the US within the last 2 decades for the treatment of r/r MCL (see 
Table 2), and temsirolimus is approved in the European Union (EU).  Bortezomib is an inhibitor 
of the 26S proteasome and was evaluated in a single-arm, open-label, multicenter trial of 
155 patients with r/r MCL who had received at least 1 prior therapy {Fisher 2006}.  Thirty-seven 
percent had disease refractory to the last treatment regimen.  The ORR based on independent 
radiologic review of computed tomography (CT) scans was 31%, including 6% complete 
response (CR).  The median DOR was 9.3 months, and the median time to progression was 
6.1 months {VELCADE 2017}.  The most common Grade 3 or greater toxicities were peripheral 
neuropathy (13%), fatigue (12%), and thrombocytopenia (11%).  
Lenalidomide, a second-generation thalidomide derivative, was studied in a single-arm, open- 
label, multicenter, trial of 134 patients with r/r MCL {Goy 2013}.  Patients were required to have 
received prior treatment with an anthracycline or mitoxantrone, cyclophosphamide, rituximab, 
and bortezomib.  Fifty-three percent had 4 or more prior therapies, 60% had disease refractory to 
bortezomib, and 29% had a prior autoSCT.  The ORR based on independent radiologic review of 
CT scans was 26%; 1% achieved a CR {REVLIMID 2015}.  The median DOR was 16.6 months, 
and the median progression-free survival (PFS) was 4 months.  The most common Grade 3 or 
Grade 4 adverse events (AEs) were neutropenia (43%), thrombocytopenia (28%), anemia (11%), 
pneumonia (8%), and fatigue (7%). 
Ibrutinib is a covalent inhibitor of Bruton’s tyrosine kinase.  The safety and efficacy of ibrutinib 
was evaluated in a single-arm, open-label, multicenter, trial of 111 patients with r/r MCL who 
had received at least 1, but no more than 5 prior therapies {Wang 2013}.  The ORR based on 
investigator review of CT scans was 68%, including 21% CR.  The median DOR was 
17.5 months, and the median PFS was 13.9 months.  The most common Grade 3 or higher 
toxicities were neutropenia (16%), thrombocytopenia (11%), and diarrhea (6%).  
Despite available therapies, almost all patients with r/r MCL die from PD (refer to Table 3).  
Martin et al, conducted a large (n = 114) retrospective cohort study of response and survival in 
patients treated after primary or acquired ibrutinib resistance {Martin 2016}.  Of the 104 patients 
with data available, 73 patients underwent subsequent treatment after stopping ibrutinib, and 
61 subjects were evaluable for efficacy.  Outcomes were poor, with an ORR of 26%, CR rate of 
7%, and median OS of 5.8 months.  Cheah et al, reported similar results (ORR 32% and median 
OS of 8.4 months) in a cohort of 31 patients {Cheah 2015}.  There are limited other data on the 
efficacy of bortezomib, lenalidomide, or other agents in patients who have progressed on 
ibrutinib therapy.  There is an urgent unmet need for new treatment options that can induce 
durable responses in a significant fraction of patients.  


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More recently, acalabrutinib, an oral Bruton’s tyrosine kinase inhibitor (BTKi), was approved in 
the US for the treatment of relapsed or refractory MCL {Calquence 2017}.  This agent was 
studied in an open-label, multicenter, Phase 2 study of 124 patients with MCL who had at least 
1 prior therapy (median of 2 prior lines of therapy; range:  1 to 5 prior lines), and those who had 
previously been treated with any BTKi were excluded from the study {Calquence 2017, Wang 
2018}.  Thus, this population was less heavily pretreated compared with patients in the trials of 
bortezomib, lenalidomide, and ibrutinib.  After a median follow-up of 15.2 months, the ORR was 
81% and the CR rate was 40% {Calquence 2017}.  Among all treated patients, the medians for 
DOR, PFS, and OS were not reached, and the 12-month PFS and OS rates were 67%, and 87%, 
respectively.  The most common Grade 3 and higher AEs were neutropenia (13 patients, 10%), 
anemia (11 patients, 9%), and pneumonia (6 patients, 5%) {Wang 2018}.
In November 2019, zanubrutinib, an oral BTKi, was approved in the US for the treatment of 
adult patients with MCL who have received at least 1 prior therapy. Approval was based on a 
single-arm, open-label, multicenter Phase 2 trial of 86 subjects with r/r MCL who had received at 
least 1 prior therapy (median of 2 prior lines of therapy; range: 1 to 4 prior lines) {BRUKINSA 
2019}. Similar to the acalabrutinib pivotal trial, subjects who had prior exposure to a BTKi were 
excluded, although it was noted that this trial included a higher proportion of subjects with 
refractory disease (52% vs 24% in the acalabrutinib trial) {Song 2020}. The ORR as assessed by 
independent review was 84% and the CR rate was 69%. The median DOR was 19.5 months with 
a median follow-up for response of 16.4 months, and the median PFS was 22.1 months based on 
a median follow-up of 19.2 months. The most common Grade 3 and higher AEs were 
neutropenia (17 subjects, 20%) and lung infection/pneumonia (8 subjects, 9%).
Table 2.
Outcomes with Available Therapies in r/r MCL
Regimen
N
Outcome
Reference
Bortezomiba
155
ORR 31%;  CR 8%, DOR 9.3m
{Fisher 2006}
Lenalidomideb
134
ORR 26%; CR 7%; DOR 16.6m
{Goy 2013}
Ibrutinib
111
ORR 68%; CR 21%; DOR 17.5m
{Wang 2013}
Acalabrutinib
124
ORR 81%; CR 40%; DOR NR
{Wang 2018}
Zanubrutinib
86
ORR 84%; CR 69%; DOR 19.5m
{Song 2020}
Abbreviations:  CR, complete response; DOR, duration of response; m, month; MCL, mantle cell lymphoma; NR, no response; 
ORR, objective response rate; r/r, relapsed/refractory.
a
Retrospective cohort studies of patients with primary or acquired ibrutinib resistant MCL treated with salvage therapy.  
b
Patients enrolled in this study had not failed ibrutinib.
Table 3.
Treatment Outcomes in r/r MCL After Progressing on Ibrutinib
N
Outcome
Reference
61
ORR 26%;  CR rate 7%, mOS 5.8m
{Martin 2016}
31
ORR  32% 19% CR rate; mOS 8.4m
{Cheah 2015}
Abbreviations:  CR, complete response; m, month; MCL, mantle cell lymphoma; mOS, median overall survival; ORR, objective 
response rate; r/r, relapsed/refractory.


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2.2.1.
Rationale for Cohort 3
Despite relatively high ORRs, treatment with BTKi is not considered curative. As noted in 
Section 2.2, most patients experience disease progression following BTKi treatment, and these 
patients have limited treatment options and poor outcomes to salvage therapy. Furthermore, 
approximately one-third of patients demonstrate primary resistance to BTKi {Martin 2016}.
Certain features of aggressive MCL such as p53 mutations, blastoid morphology, and high Ki-67 
index are associated with poor response to BTKi {Liebers 2018, Rule 2017, Rule 2019, Wang 
2016}. A pooled analysis of 370 subjects with r/r MCL who received ibrutinib across 3 clinical 
studies demonstrated an association between disease morphology and clinical outcomes: 
compared with subjects who had nonblastoid MCL, subjects with blastoid MCL had shorter 
median DOR (8.5 vs 18.8 months), median PFS (5.1 vs 14.6 months), and median OS 
(12.8 months vs not reached at 2 years) {Rule 2017}. In a follow-up to this analysis, p53 
mutational status was also found to be associated with clinical outcomes: compared with subjects 
bearing wildtype p53, subjects with mutated p53 had worse ORR (55% [with no CRs] vs 70%), 
median PFS (4.0 vs 12.0 months), and median OS (10.3 vs 33.6 months) {Rule 2019}. 
Additionally, in a study of 50 subjects with r/r MCL who were treated with ibrutinib in 
combination with rituximab, subjects with a Ki-67 index ≥ 50% had worse outcomes compared 
with subjects with a Ki-67 index < 50% (ORRs of 50% vs 100% and CR rates of 17% vs 54%) 
{Wang 2016}. These results are further compounded by the finding that poor prognostic factors 
increase with increasing lines of therapy {Kumar 2019, Rule 2017}.
Thus, new treatment strategies based on novel targets or different mechanisms of action are 
needed to induce earlier, more durable responses in r/r MCL with aggressive clinical features. 
Cohort 3 of this study will specifically evaluate the efficacy and safety profile of a chimeric 
antigen receptor (CAR) T-cell therapy, KTE-X19, in subjects with BTKi-naïve r/r MCL.
2.2.1.1.
Selection of Historical Control ORR
A meta-analysis was performed to determine the historical control ORR among patients with r/r 
MCL. This meta-analysis included published clinical studies that reported ORRs of therapies for 
BTKi-naïve patients with r/r MCL, including studies of commonly used regimens for r/r MCL 
such as BR, bortezomib plus rituximab, and lenalidomide plus rituximab. The studies included in 
this meta-analysis are outlined in Table 4. The results of this meta-analysis demonstrated a 
historical control ORR of 57%. Thus, a historical control ORR of 57% will be used for 
hypothesis testing for the primary efficacy endpoint in Cohort 3.


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Clinical Protocol
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Table 4.
Studies Included in the Meta-analysis to Determine Historical Control 
ORR
Primary Author
Treatment
ITT (N)
Number of 
Responders (n)
{Wang 2018}
Acalabrutinib
124
100
{Ohmachi 2010}
Bendamustine
11
11
{Goy 2005}
Bortezomib
29
12
{Goy 2009}
Bortezomib
141
45
{Strauss 2006}
Bortezomib
24
7
{Kouroukis 2011}
Bortezomib + gemcitabine
25
15
{Agathocleous 2010}
Bortezomib + rituximab
19
11
{Baiocchi 2011}
Bortezomib + rituximab
14
4
{Chiappella 2010}
Bortezomib + rituximab
25
16
{Czuczman 2015}
BR
45
37
{Robinson 2008} 
BR
12
11
{Rummel 2005}  
BR
16
12
{Rummel 2016}
BR
24
17
{Forstpointner 2004}
FCM
24
11
{Dreyling 2016}
Ibrutinib
139
107
{Furtado 2012}
Ibrutinib
8
5
{Maruyama 2016}
Ibrutinib
16
14
{Wang 2014}
Ibrutinib
120
75
{Wang 2015}
Ibrutinib
111
74
{Goy 2017}
Ibrutinib + lenalidomide + rituximab
16
6
{Jerkeman 2018}
Ibrutinib + lenalidomide + rituximab
50
38
{Jain 2018}
Ibrutinib + rituximab
50
44
{Eve 2012}
Lenalidomide
26
8
{Goy 2015}
Lenalidomide
136
38
{Habermann 2009}
Lenalidomide
15
8
{Trneny 2016}
Lenalidomide
170
78
{Zinzani 2013}
Lenalidomide
57
25
{Sharman 2019} 
Lenalidomide + rituximab
70
38
{Wang 2015}
Lenalidomide + rituximab
46
26
{Visco 2013}
R-BAC
20
16
{Igarashi 2002}
Rituximab
13
6


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Primary Author
Treatment
ITT (N)
Number of 
Responders (n)
{Rummel 2016}
Rituximab + fludarabine
23
6
{Ansell 2008}
Temsirolimus
27
11
{Dreyling 2016}
Temsirolimus
141
65
{Jurczak 2018}
Temsirolimus
90
23
{Verhoef 2008}
Temsirolimus
54
12
{Verhoef 2008}
Temsirolimus
54
3
{Witzig 2005}
Temsirolimus
34
13
{Davids 2017}
Venetoclax
28
21
{Tam 2018}
Venetoclax + ibrutinib
24
17
{Song 2020}
Zanubrutinib
86
72
{Tam 2019}
Zanubrutinib
37
32
Abbreviations: BR, bendamustine + rituximab; FCM, cyclophosphamide + fludarabine + mitoxantrone; ITT, intent-to-treat; 
ORR, objective response rate; R-BAC, rituximab + bendamustine + cytarabine.
2.3.
Novel T-cell Immunotherapies
T cells play a central role in the immune system by destroying diseased cells, including tumor 
cells, throughout the body {Kershaw 2013}. Studies with tumor vaccines {Kantoff 2010}, 
immune checkpoint inhibitors {Hamid 2013, Wolchok 2013}, tumor-infiltrating lymphocytes 
{Rosenberg 2011}, the bispecific CD19-directed CD3 T-cell engager blinatumomab 
{BLINCYTO 2019}, and CAR T cells {KYMRIAH 2018, YESCARTA 2019a, YESCARTA 
2019b} have demonstrated the potential of T cells to treat cancer.
Engineered autologous T-cell immunotherapy, which uses a patient’s own immune cells, offers a 
promising approach to treating many types of cancer. To be effective, such T cells must possess 
the appropriate specificity for a tumor, be present in sufficient numbers, and be able to overcome 
any local immunosuppressive factors. Selecting an appropriate target antigen for T-cell therapy 
is critical to the potency of the therapy. One type of engineered autologous T-cell therapy 
comprises T cells that have been engineered ex vivo to express a CAR directed toward a tumor 
surface antigen. These CARs are fusion proteins with antigen-binding, transmembrane, and 
T-cell activation domains that, when expressed in T cells, can target tumor antigens for 
T-cell-mediated killing {Kershaw 2013}. CAR T cells have demonstrated promising antitumor 
activity across numerous B-cell malignancies, including NHL {Kochenderfer 2012, 
Kochenderfer 2015, Kochenderfer 2017a, Kochenderfer 2017b, Locke 2019, Neelapu 2017, 
Turtle 2016}, chronic lymphocytic leukemia (CLL) {Kochenderfer 2015, Porter 2015, Porter 
2011}, and acute lymphoblastic leukemia {Davila 2014, Gupta 2007, Lee 2015, Maude 2014, 
Maude 2015, Singh 2016}.


KTE-C19-102 
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2.4. 
CD19 and Expression 
CD19 is a 95 kD trnnsmembrane protein expressed in the B-cell lineage. It is expressed in 
n01m al B cells staiiing at the pro-B-cell stage until the final differentiation stage and is not 
expressed in pluripotent hematopoietic stem cells or most plasma cells. The pattern of CD 19 
expression is maintained in B-cell malignancies, including all subtypes of B-cell NHL, CLL, and 
non-T-cell acute lymphoblastic leukemia {Blanc 2011} with the exception of multiple myeloma. 
2.5. 
Anti-CD19 CART-cell Product 
Anti-CD19 CAR T cells are autologous human T cells that have been engineered to express an 
extracellulai· single-chain vai·iable fragment with specificity for CD 19 linked to an intracellular 
signaling paii comprised of signaling domains from CD28 and CD3s (CD3-zeta) molecules 
ananged in tandem. 
An anti-CD19 CAR vector construct has been designed, optimized, and initially tested at the 
Surge1y Branch of the National Cancer Institute (NCI; 09-C-0082; investigational new diug 
[IND] 13871) (Figure 2) {Kochenderfer 2009, Kochenderfer 2010} is derived from the vai·iable 
region of the anti-CD19 monoclonal antibody FMC63 {Nicholson 1997}CD19 CAR T cells 
{Kowolik 2006}-cell activation. These fragments were cloned into the murine stem cell vims-
based vector, utilized to genetically engineer the autologous T cells. Treatment with anti-CD 19 
CAR T cells is cmTently being administered to subjects with CD 19+ B-cell malignancies in 
ongoing NCI protocol (09-C-0082; IND 13871). The same CAR vector construct will be used in 
this study. 
Figure 2. 
Anti-CD19 CAR 
CO2~ 
5'LTR 
scfv 
CD3{ 
3'LTR 
CAR vector construct 
Viral vector 
Target binding domain: 
antibody derived (scFv) 
CAR-engineered 
Tcell 
Tumor cell 
ctivity 
Cyto ,n release 
Prolife~ati'on 
Abbreviations: CAR, chimeric antigen receptor; LTR, long tenninal repeat; scFV, single-chain variable region fragment. 
CONFIDENTIAL 
Page 25 
07 November 2022 


KTE-C19-102 
Kite Pha1ma, Inc. 
Clinical Protocol 
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2.5.1. 
Axicabtagene Ciloleucel 
Axicabtagene ciloleucel is manufactured for subjects with lymphomas that are characterized as 
not being associated with circulating tumor cells (ie, diffuse large B-cell lymphoma, prima1y 
me • 
• 
-
ll lymphoma and follicul 
• 
• 
ar 
transduced with a retroviral vector containing an anti-CD19 CAR gene and propagated in culture 
to generate sufficient engineered T cells for administration. 
Patients with r/r MCL may have tumor cells in the peripheral blood, which is associated with a 
poor prognosis {Argatoff 1997}. When the first 10 subjects in Cohort 1 were dosed with 
axicabtagene ciloleucel, it was observed that the incidence and amount of circulating leukemic 
phase MCL appeared to be higher than rates that are typically for MCL {Argatoff 1997, Cheah 
2015, Cheah 2016}. Because the axicabtagene ciloleucel manufacturing process is not optimized 
to remove circulating tumor cells from the manufacturing process stream, all subsequent patients 
were dosed using KTE-X19. 
2.5.2. 
KTE-X19 
KTE-X19 is manufactured for subjects with lymphomas that are characterized by having high 
number 
CD 19-expressing circulatin tumor ce 
• 
• 
L, 
, an are t en trans uce 
a retroviral vector containing an anti-CD19 CAR gene. These engineered T cells are then 
propagated in culture to generate a sufficient number of cells for administration. 
2.6. 
Prior Experience with KTE-X19 and Other Anti-CD19 CART Cells 
Refer to the cmTent KTE-X19 Investigator's Brochure (IB) for the most cmTent anti-CD19 CAR 
T cells nonclinical and clinical infonnation. 
2.7. 
KTE-X19 
Kite Phanna, Inc., (hereafter refe1Ted to as Kite) is developing an engineered autologous cell 
therapy (eACT) (KTE-X19) that targets CD19 expression on B-cell malignancies. The CAR 
vector construct is identical to the one used in the NCI protocol (09-C-0082; IND 13871). Kite, 
in conjunction with the NCI Surge1y Branch, has developed a rapid, closed, and bead-less 
process for the generation of the anti-CD19 CART cells. Closing the process retains the 
characteristics of the T-cell product {Better 2014}. Refer to the cmTent 1B for more details. 
CONFIDENTIAL 
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3.
STUDY DESIGN
3.1.
General Study Design
Study KTE-C19-102 (hereafter referred to as ZUMA-2) is a Phase 2, multicenter, open-label 
study evaluating the safety and efficacy of KTE-X19 in subjects with r/r MCL. 
This study is designed to examine the safety and efficacy of KTE-X19 in patients who have r/r 
MCL that has progressed on prior chemotherapy and anti-CD20 antibody therapy with or 
without ibrutinib or acalabrutinib. The study will evaluate the ORR and durability of response 
after treatment with KTE-X19. An open-label, 3-cohort design is used, with the following 
cohorts: 

Cohort 1 and Cohort 2 will include subjects with r/r MCL who have been treated with up to 
5 prior regimens including a BTKi. Prior therapy must have included all of the following: 
anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody 
therapy, and ibrutinib or acalabrutinib. 

Cohort 3 will include subjects with r/r MCL who have been treated with up to 5 prior 
regimens but have not received prior therapy with a BTKi. Prior therapy must have included 
anthracycline-, bendamustine-, or high-dose cytarabine-containing chemotherapy and 
anti-CD20 monoclonal antibody therapy.
Up to approximately 220 subjects with r/r MCL in total will be enrolled and treated to evaluate 
the efficacy of KTE-X19:

Cohort 1 will treat up to approximately 90 subjects at a target dose of 2 x 106 anti-CD19 
CAR T cells/kg, including up to approximately 80 KTE-X19 subjects and 10 axicabtagene 
ciloleucel subjects. The Cohort 1 KTE-X19 subjects will form the basis for statistical 
hypothesis testing on the primary endpoint in Cohort 1, with a target ORR in the alternative 
hypothesis of 50% and a futility criterion that the ORR is no more than 25%. As of 
28 May 2019, Cohort 1 has completed enrollment.

Cohort 2 will treat up to 40 KTE-X19 subjects at a target dose of 0.5 x 106 anti-CD19 CAR 
T cells/kg. As of 01 May 2018, Cohort 2 has completed enrollment.

Cohort 3 will enroll and treat up to approximately 90 KTE-X19 subjects at a target dose of 
2 x 106 anti-CD19 CAR T cells/kg, with a target ORR in the alternative hypothesis of 75% 
and a null hypothesis that the ORR is 57% or less.
Each subject will proceed through the following study periods:

Screening 

Enrollment/Leukapheresis 

Bridging therapy, if applicable


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
Conditioning chemotherapy 

Investigational product (IP) treatment 

Post-treatment assessment 

Long-term follow-up (LTFU)
An independent Data Safety Monitoring Board (DSMB) will review safety and/or efficacy data 
from Cohort 1 and Cohort 2 at 4 times during this study.  The DSMB will first meet to review 
safety data when 10 Cohort 1 subjects have been enrolled and treated with anti-CD19 CAR 
T cells and followed for 30 days.  The DSMB will meet for the second time to review safety and 
efficacy data after 20 Cohort 1 subjects have been enrolled and treated with anti-CD19 CAR 
T cells and have had the opportunity to complete the 3-month disease assessment.  The DSMB 
will meet for the third time to review both safety and efficacy data after 10 subjects in Cohort 2 
have been enrolled and treated with KTE-X19 and have had the opportunity to be followed for 
30 days. The DSMB will meet for the fourth time to review safety data after 44 subjects in 
Cohort 1 have been enrolled and treated with anti-CD19 CAR T cells and have had the 
opportunity to be followed for at least 30 days, with focus on the safety data from the 
6 KTE-X19 subjects treated most recently in this cohort. The DSMB will be chartered to make 
trial conduct recommendations for Cohort 1 and Cohort 2 based on an analysis of risk vs benefit.  
The DSMB may meet more often as needed. For details surrounding the DSMB, refer to 
Section 9.10 and Section 9.12.
A scientific steering committee, comprising the study sponsor and at least 3 study investigators, 
will be specifically chartered to review the safety data from Cohort 3 and make 
recommendations on further study conduct. The scientific steering committee will meet after 
15 subjects in Cohort 3 have been enrolled, treated with KTE-X19, and have had the opportunity 
to be followed for 30 days, and again after 50 subjects in Cohort 3 have been enrolled, treated 
with KTE-X19, and have had the opportunity to be followed for 3 months. The scientific steering 
committee may meet more often as needed. For details surrounding the scientific steering 
committee, refer to Section 9.11 and Section 9.12.
For study requirements assigned to each study period, refer to the schedules of assessments 
(SOAs) and Section 7 for details.
A study schema is included in Figure 1.
3.2.
Participating Sites
Approximately 40 centers located in North America and Europe will participate in this study.  
During the conduct of the study, additional regions, countries, or sites may be added as 
necessary.
Sites that do not enroll a subject within 3 months of their site being activated, will be considered 
for closure.


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3.3.
Number of Subjects
Participants in this trial will be referred to as “subjects.”  It is anticipated that up to 
approximately 220 subjects will be enrolled and treated in this study.
It should be noted that Kite may choose to close enrollment at any time.  Refer to Section 10 for 
statistical considerations of the protocol, including sample size estimations.
3.4.
Replacement of Subjects
Subjects will continue to be enrolled until the specified numbers of subjects are attained in the 
modified intent-to-treat (mITT) set.  Subjects who have not received the target dose of 
anti-CD19 CAR T cells will be retained in the analyses of disposition and safety, where 
appropriate (refer to Section 10.5). 
3.5.
Study Duration
3.5.1.
Study Duration for Individual Subjects 
The duration of participation for individual subjects will vary depending on a subject’s screening 
requirements, response to treatment, survival, and, if applicable, timing of transition to the 
separate LTFU study, KT-US-982-5968 (discussed in Section 3.5.3). 
The need for prolonged follow-up is based on the potential persistence of gene transfer vectors in 
treated subjects.
3.5.2.
Completion of Study
Completion of the study for subjects in Cohorts 1 and 2 is defined as the time at which the last 
subject in Cohorts 1 and 2 completes at least 24 months of assessments and transitions to 
KT-US-982-5968, is considered lost to follow-up, withdraws consent, or dies.
Completion of the study for subjects in Cohort 3 is defined as the time at which the last subject 
in Cohort 3 completes at least 24 months of assessments and transitions to KT-US-982-5968, is 
considered lost to follow-up, withdraws consent, or dies.
Upon activation of KT-US-982-5968 at the subject’s study site, the subject will be offered the 
opportunity to complete LTFU assessments under the KT-US-982-5968 protocol.
3.5.3.
LTFU
All subjects who received an infusion of anti-CD19 CAR T cells will be provided the 
opportunity to transition to a separate LTFU study, KT-US-982-5968, where they will be 
monitored for occurrence of late-onset targeted AEs/serious AEs (SAEs) suspected to be 
possibly related to anti-CD19 CAR T cells as defined in KT-US-982-5968, presence of 
replication-competent retrovirus (RCR), and/or insertional mutagenesis for up to 15 years from 
the time of anti-CD19 CAR T-cell infusion (also refer to Section 7.12.9).


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In KT-US-982-5968, subjects will continue assessments at timepoints contiguous with the LTFU 
timepoints in this study. 


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Clinical Protocol
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4.
SUBJECT SCREENING AND ENROLLMENT
All subjects must sign and date the Independent Review Board/Independent Ethics Committee 
(IRB/IEC) approved consent form before initiating any study-specific procedures or activities 
that are not part of a subject’s routine care.  Refer to Section 7 for details.
Each subject who enters the screening period, which starts when the subject signs the informed 
consent form (ICF), will receive a unique subject identification (ID) number.  This number will 
be used to identify the subject throughout the study and must be used on all study documentation 
related to the subject. The subject identification will never be changed even if the subject is 
rescreened.
Furthermore, the subject ID number must remain constant throughout the entire clinical study; it 
must not be changed after enrollment or if the subject is rescreened or retreated.


KTE-C19-102 
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Clinical Protocol
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5.
SUBJECT ELIGIBILITY
5.1.
Inclusion Criteria
101)
Pathologically confirmed MCL, with documentation of either overexpression of cyclin 
D1 or presence of t(11;14)
102)
Up to 5 prior regimens for MCL.  
Cohort 1 and Cohort 2: Prior therapy must have included:
■
Anthracycline or bendamustine-containing chemotherapy, and
■
Anti-CD20 monoclonal antibody therapy, and
■
Ibrutinib or acalabrutinib
Cohort 3: Prior therapy must have included anthracycline-, bendamustine-, or high-dose 
cytarabine-containing chemotherapy and anti-CD20 monoclonal antibody therapy. 
Subjects in Cohort 3 must not have received prior therapy with a BTKi.
103)
Relapsed or refractory disease, defined by the following:
Disease progression after last regimen, or
Refractory disease is defined failure to achieve a partial response (PR) or CR to the last 
regimen
104)
At least 1 measurable lesion.  Lesions that have been previously irradiated will be 
considered measurable only if progression has been documented following completion of 
radiation therapy
If the only measurable disease is lymph node disease, at least 1 lymph node should be 
≥ 2 cm
105)
For subjects in Cohort 1 and Cohort 2 only: Magnetic resonance imaging (MRI) of the 
brain showing no evidence of central nervous system (CNS) lymphoma
106)
At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior 
systemic therapy or BTKi (ibrutinib or acalabrutinib; as applicable for subjects in 
Cohort 1 and Cohort 2) at the time the subject is planned for leukapheresis, except for 
systemic inhibitory/stimulatory immune checkpoint therapy.  At least 3 half-lives must 
have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint 
molecule therapy at the time the subject is planned for leukapheresis (eg, ipilimumab, 
nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists). 


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107)
Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for 
clinically non-significant toxicities such as alopecia)
108)
Age 18 years or older
109)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
110)
Absolute neutrophil count (ANC) ≥ 1,000/μL
111)
Platelet count ≥ 75,000/μL. For subjects in Cohort 3 with bone marrow involvement, 
platelet count ≥ 50,000/μL is acceptable.
112)
Absolute lymphocyte count ≥ 100/μL
113)
Adequate renal, hepatic, pulmonary, and cardiac function defined as:
Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min 
Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 upper 
limit of normal (ULN) 
Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert’s syndrome
Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an 
echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings. 
For subjects in Cohort 3, a multigated acquisition (MUGA) scan may be used in place of 
ECHO.
No clinically significant pleural effusion for subjects in Cohort 1 and Cohort 2, and no 
clinically significant pleural effusion, pericardial effusion, or ascites for subjects in 
Cohort 3
Baseline oxygen saturation > 92% on room air
114)
Females of childbearing potential must have a negative serum or urine pregnancy test.  
Females who have undergone surgical sterilization or who have been postmenopausal for 
at least 2 years are not considered to be of childbearing potential.
5.2.
Exclusion Criteria
201)
History of malignancy other than nonmelanomatous skin cancer or carcinoma in situ 
(eg, cervix, bladder, breast) unless disease-free for at least 3 years 
202)
AutoSCT within 6 weeks of planned KTE-X19 or axicabtagene ciloleucel infusion 
203)
History of alloSCT, with the exception of subjects in Cohort 3 with no donor cells 
detected on chimerism > 100 days after alloSCT


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Clinical Protocol
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204)
Prior CD19 targeted therapy with the exception of subjects who received KTE-X19 or 
axicabtagene ciloleucel in this study and are eligible for retreatment
205)
Prior CAR therapy or other genetically modified T-cell therapy
206)
History of severe, immediate hypersensitivity reaction attributed to aminoglycosides 
207)
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring 
intravenous (IV) antimicrobials for management.  Simple urinary tract infection (UTI) 
and uncomplicated bacterial pharyngitis are permitted if responding to active treatment 
and after consultation with the Kite medical monitor
208)
History of human immunodeficiency virus (HIV) infection or acute or chronic active 
hepatitis B or C infection. Subjects with a history of hepatitis infection must have cleared 
their infection as determined by standard serological and genetic testing. For subjects in 
Cohort 3 enrolled in France, those with any history of acute or chronic hepatitis B or C 
infection are excluded. 
209)
Presence of any in-dwelling line or drain (eg, percutaneous nephrostomy tube, 
in-dwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial 
catheter).  Ommaya reservoirs and dedicated central venous access catheters, such as a 
Port-a-Cath or Hickman catheter, are permitted. 
210)
Subjects with detectable cerebrospinal fluid (CSF) malignant cells or brain metastases or 
with a history of CNS lymphoma, CSF malignant cells, or brain metastases
211)
History or presence of CNS disorder, such as seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible 
encephalopathy syndrome, or any autoimmune disease with CNS involvement 
212)
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active 
arrhythmias, or other clinically significant cardiac disease within 12 months of 
enrollment
213)
Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
214)
History of deep vein thrombosis or pulmonary embolism requiring therapeutic 
anticoagulation within 6 months of enrollment  
215)
Possible requirement for urgent therapy due to ongoing or impending oncologic 
emergency (eg, tumor mass effect, tumor lysis syndrome)
216)
Primary immunodeficiency
217)
Any medical condition likely to interfere with assessment of safety or efficacy of study 
treatment 


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218)
History of severe immediate hypersensitivity reaction to any of the agents used in this 
study 
219)
Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen
220)
Females of childbearing potential who are pregnant or breastfeeding because of the 
potentially dangerous effects of the preparative chemotherapy on the fetus or infant 
221)
Subjects of both genders who are not willing to practice birth control from the time of 
consent through 6 months after the completion of KTE-X19 or axicabtagene ciloleucel 
infusion 
222)
In the investigator’s judgment, the subject is unlikely to complete all protocol-required 
study visits or procedures, including follow-up visits, or comply with the study 
requirements for participation.
223)
History of autoimmune disease (eg Crohn’s disease, rheumatoid arthritis, systemic lupus) 
resulting in end organ injury or requiring systemic immunosuppression/systemic disease 
modifying agents within the last 2 years


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Clinical Protocol
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6.
PROTOCOL TREATMENT
6.1.
Treatment Terminology 
The following terms will be used to describe and define protocol treatment: 

Bridging therapy, if administered at the discretion of the investigator and after discussion 
with the medical monitor, will be:
Cohort 1 and Cohort 2: dexamethasone, ibrutinib, or acalabrutinib
Cohort 3: dexamethasone, radiotherapy, specified chemotherapy, or any combination 
thereof, as detailed in Section 6.2.1.2

The conditioning chemotherapy regimen used for this study will be fludarabine and 
cyclophosphamide.  

The IP for this study is named KTE-X19 and axicabtagene ciloleucel.  

The term study treatment refers to all protocol-required therapies.
6.2.
Study Treatment
6.2.1.
Bridging Therapy
6.2.1.1.
Cohort 1 and Cohort 2
Bridging therapy will be supplied by the investigative site unless otherwise noted.  Sites should 
refer to the current product label for guidance on packaging, storage, preparation, administration, 
and toxicity management. At the discretion of the investigator and after discussion with the 
medical monitor, bridging therapy may be considered for any subject, particularly those with 
high disease burden at screening (eg, > 25% marrow involvement and/or ≥ 1,000 leukemic phase 
mantle cells/mm3 in the peripheral circulation).  
Bridging therapy is to be administered after leukapheresis and must be completed at least 5 days 
prior to initiating conditioning chemotherapy.  
In Cohort 1 and Cohort 2, bridging therapy is allowed with (1) dexamethasone at a dose of 20 to 
40 mg or equivalent, either orally (PO) or IV daily for 1 to 4 days, (2) ibrutinib at a dose of 
560 mg PO daily or most recent dose if there had been a dose adjustment, or (3) acalabrutinib 
100 mg PO every 12 hours or most recent dose if there had been a dose adjustment.  Choice of 
corticosteroid and dose can be adjusted for age/comorbidities or per local or institutional 
guidelines.
If bridging therapy is administered, the subject must undergo another positron emission 
tomography-computed tomography (PET-CT) or diagnostic CT to assess disease status prior to 
receiving conditioning chemotherapy and subsequent anti-CD19 CAR T-cell infusion (refer to 
Section 7.8 for detailed timing and imaging requirements).


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6.2.1.2.
Cohort 3
At the discretion of the investigator and per institutional guidelines and standard of care and after 
discussion with the medical monitor, bridging therapy is recommended for all subjects, 
particularly those with rapidly progressing disease, clinical deterioration, or high disease burden 
at screening (eg, > 25% marrow involvement and/or ≥ 1,000 leukemic phase mantle cells/mm3 in 
the peripheral circulation). When administered in this context, bridging therapy allows for 
standard-of-care therapies to be administered to subjects during the period between leukapheresis 
and the manufacturing of KTE-X19. A retrospective analysis demonstrated the impact of 
bridging therapy in patients with high tumor burden: no significant differences in the incidence 
of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome 
(ICANS) were observed for patients who received bridging therapy compared with those who 
received no bridging therapy, demonstrating the potential for bridging therapy to reduce tumoral 
mass while maintaining the safety profile of CAR T-cell therapy {Lutfi 2020}. 
If prescribed, bridging therapy must be administered after leukapheresis and must be completed 
at least 7 days or 5 half-lives, whichever is shorter, prior to initiating conditioning chemotherapy.
Bridging therapy is allowed with the following regimens as shown in Table 5: 
(1) dexamethasone at a dose of 20 to 40 mg or equivalent, either PO or IV daily for 1 to 4 days; 
(2) palliative radiotherapy to localized lesions at a dose of up to 30 Gy in 10 fractions or 
equivalent; (3) specified chemotherapy; or (4) any combination of 1 specified chemotherapy 
and/or corticosteroid and/or radiotherapy. Bridging regimen should be discussed with the Kite 
medical monitor, and BTKis are not permitted for bridging therapy. Dose can be adjusted for 
age/comorbidities or per local or institutional guidelines. If radiotherapy is considered for 
bridging, the radiotherapy modality should be discussed with the Kite medical monitor. 
Radiotherapy should be administered per local or institutional guidelines. Irradiated lesions can 
no longer serve as target lesions, and other target lesions must be present to allow for response 
assessment. Use of any other chemotherapeutic or targeted agent or palliative radiotherapy is to 
be discussed with the Kite medical monitor.
If bridging therapy is administered, the subject must undergo another PET-CT or diagnostic CT 
to assess disease status prior to receiving conditioning chemotherapy and subsequent anti-CD19 
CAR T-cell infusion (refer to Section 7.8 for detailed timing and imaging requirements).
Bridging therapy will be supplied by the investigative site unless otherwise noted. Sites should 
refer to the current agent-specific product label(s) for guidance on packaging, storage, 
preparation, administration (including necessary dose reductions for organ dysfunction, 
pregnancy testing requirements, etc.), and toxicity management associated with the 
administration of the agent(s) selected.


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Table 5.
Bridging Therapy for Cohort 3
Bridging Regimen Options
(1) Corticosteroid
Dexamethasone at a dose of 20 to 40 mg or equivalent, either PO or IV daily for 1 to 
4 days
Choice of corticosteroid and dose can be adjusted for age/comorbidities or per local 
or institutional guidelines
(2) Radiotherapy
Radiotherapy to localized lesions up to 30 Gy in 10 fractions or equivalent
Cytarabine 1 to 2 g/m² IV for a maximum of 2 days
(3) Chemotherapy
Cyclophosphamide 1 to 2 g/m² IV for a maximum of 2 days, or hyperfractionated 
cyclophosphamide 300 mg/m2 administered every 12 hours for 6 doses
(4) Any combination of the following: 1 of the above chemotherapies AND/OR choice of corticosteroid as stated 
above AND/OR radiotherapy to localized lesions as stated above
Abbreviations: IV, intravenous; PO, oral.
Note: Use of any other chemotherapeutic or targeted agent or palliative radiotherapy is to be discussed with the Kite medical 
monitor.
6.2.2.
Conditioning Chemotherapy
Conditioning chemotherapy will be supplied by the investigative site unless otherwise noted.  
Sites should refer to the current product label for guidance on packaging, storage, preparation, 
administration, and toxicity management associated with the administration of both agents.
Subjects will receive a non-myeloablative conditioning regimen consisting of fludarabine 
30 mg/m2/day and cyclophosphamide 500 mg/m2/day, administered x 3 days to induce 
lymphocyte depletion and create an optimal environment for expansion of anti-CD19 CAR 
T cells in vivo. Conditioning chemotherapy should only commence when the KTE-X19 product 
is available, if required by country regulatory agencies. 
6.2.2.1.
Fludarabine 
Fludarabine phosphate (hereafter, fludarabine) is a synthetic purine nucleoside that differs from 
physiologic nucleosides in that the sugar moiety is arabinose instead of ribose or deoxyribose.  
Fludarabine is a purine antagonist antimetabolite.
Refer to the most recent version of the package insert for specific details surrounding the 
administration of fludarabine.
6.2.2.2.
Cyclophosphamide
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent.  Following conversion to 
active metabolites in the liver, cyclophosphamide functions as an alkylating agent; the drug also 
possesses potent immunosuppressive activity.  The serum half-life after IV administration ranges 
from 3 to 12 hours; the drug and/or its metabolites can be detected in the serum for up to 
72 hours after administration.  


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Refer to the most recent version of the package insert for specific details surrounding the 
administration of cyclophosphamide.
6.2.2.3.
Mesna
Mesna is a detoxifying agent used to inhibit the hemorrhagic cystitis induced by chemotherapy.  
The active ingredient mesna is a synthetic sulfhydryl compound designated as sodium-2-
mercaptoethane sulfonate with a molecular formula of C2H5NaO3S2. 
Mesna will be administered around the cyclophosphamide dose according to institutional 
standards.  Refer to the most recent version of the package insert for specific details surrounding 
the administration of mesna.
6.2.3.
KTE-X19 
Refer to the current version of the IB regarding KTE-X19 and related clinical experience.  Refer 
to the Investigational Product Manual for details and instruction on storage and administration of 
KTE-X19.  
KTE-X19 is supplied cryopreserved in cryostorage bags.  The product in the bag is slightly 
cloudy, with cream to yellow color.  The cryostorage bags containing KTE-X19 arrive frozen in 
a liquid nitrogen dry shipper.  The bags must be stored in vapor phase of liquid nitrogen, and the 
product remains frozen until the subject is ready for treatment to assure viable live autologous 
cells are administered to the subject.  Several inactive ingredients are added to the product to 
assure viability and stability of the live cells through the freezing, thawing, and infusion process.
KTE-X19 is a subject-specific product, and the intended subject will be identified by a unique 
subject ID number.  Upon receipt, verification that the product and subject-specific labels match 
the subject’s information (eg, initials, subject ID number) is essential.  Do not infuse the product 
if the information on the subject-specific label does not match the intended subject.  The volume 
of KTE-X19 infused, the thaw start/stop time, and KTE-X19 administration start/stop time will 
all be noted in the subject medical record.  The product must not be thawed until the subject is 
ready for the infusion.  Refer to the Investigational Product Manual for details and instruction on 
storage, thawing, and administration of KTE-X19.  
If any problems related to the use of KTE-X19 or any products that support the management of 
KTE-X19 (eg, cryostorage bags, subject identification labels) required in this study are 
identified, refer to the current Investigational Product Manual for information regarding issue 
reporting and resolution.
In exceptional cases, a KTE-X19 product lot that does not meet certain release specification 
criteria may be administered to a subject, when necessary to avoid an immediate significant 
hazard to the subject and having considered alternative options including the product lot 
remanufacture. Relevant country regulations will be followed and notifications to concerned 
regulatory agencies and IRBs/IECs will be performed as necessary per local requirements, in 
case such out-of-specification product lot is supplied and administered to a subject.


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6.2.3.1.
Dose Rationale
This study is designed to evaluate safety:efficacy of two anti-CD19 CAR T cell doses, both of 
which are administered after the same lymphodepleting regimen.  The higher cell dose of 
2 x 106 anti-CD19 CAR T cells/kg is evaluated in Cohort 1 and Cohort 3.  The lower dose of 
0.5 x 106 anti-CD19 CAR T cells/kg is evaluated in Cohort 2.
The recommended treatment regimen for Cohort 1 and Cohort 3 (lymphodepletion with 
cyclophosphamide 500 mg/m2 dose and fludarabine 30 mg/m2 given concurrently for 3 days 
followed by a target dose of 2 x 106 anti-CD19 CAR T cells/kg, with a maximum dose of 
2 x 108 anti-CD19 CAR T cells for subjects ≥ 100 kg) is based on the favorable safety:efficacy 
profile seen in the ZUMA-1 trial—a Phase 1/2 multicenter study investigating the safety and 
efficacy of axicabtagene ciloleucel in subjects with refractory aggressive NHL, which met its 
primary endpoint with an ORR of 82% and CR rate of 54% {Locke 2017}. The recommended 
treatment regimen for Cohort 3 is further supported by the favorable safety:efficacy profile seen 
in subjects treated with KTE-X19 in ZUMA-2 Cohort 1.
At the time of the interim analysis 3, 13 subjects (46%) had experienced Grade 3 or Grade 4 
neurologic toxicities (data on file).  A pharmacokinetic analysis of KTE-X19 in subjects dosed 
with KTE-X19 in ZUMA-2 Cohort 1 (data cutoff: 15 June 2017) demonstrated an approximate 
3- to 4-fold higher peak expansion and cumulative exposure (area under curve from Day 0 to 
Day 28 [AUC0-28]) relative to that seen in subjects treated in ZUMA-1.  Given that CAR T cell 
peak and AUC0-28 are associated with Grade 3 or higher neurologic toxicities in ZUMA-1 
patients {Neelapu 2016}, the sponsor opted to reduce the KTE‑X19 target dose to 0.5 x 106  
anti-CD19 CAR T cells/kg to evaluate safety:efficacy of a lower dose.  Therefore, subjects 
enrolled into ZUMA-2 Cohort 2 are administered a target dose of 0.5 x 106 anti-CD19 CAR T 
cells/kg, with a maximum dose of 0.5 x 108 anti-CD19 CAR T cells for subjects ≥ 100 kg.  
6.2.4.
Concomitant Therapy
Investigators may additionally prescribe any other concomitant medications or treatment deemed 
necessary to provide adequate supportive care, including growth factor support (eg, granulocyte 
colony-stimulating factor [G-CSF]) and routine anti-emetic prophylaxis and treatment except 
those medications listed in the excluded medication Section 6.2.5. 
All concurrent therapies, including medications, intubation, dialysis, oxygen, and blood products, 
should be recorded from the date of the informed consent through 3 months after completing 
treatment with anti-CD19 CAR T cells.  After 3 months of follow-up, only targeted concomitant 
therapies will be collected for 5 years after the anti-CD19 CAR T-cell infusion or until disease 
progression or subsequent therapy, whichever occurs first.  Targeted concomitant therapies 
include gammaglobulin, immunosuppressive drugs, anti-infective drugs, vaccinations, and 
anticancer therapies (eg, chemotherapy, immunotherapy, targeted therapy, hormone therapy, 
SCT/bone marrow transplant, high-dose corticosteroids, radiation, surgery, and investigational 
products).
For subjects who are enrolled, but not dosed with anti-CD19 CAR T cells, concurrent therapies 
will only be recorded from the date of the informed consent through 30 days after the last 
study-specific procedure (eg, leukapheresis, conditioning chemotherapy) or until initiation of a 


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new anticancer therapy, whichever occurs first.  For subjects who are not enrolled (eg, screen 
failure or not leukapheresed), only concurrent therapies related to SAEs will be recorded from 
the date of the screening informed consent through 30 days after the last study-specific screening 
procedure.
Specific concomitant medication collection requirements and instructions are included in the 
case report form (CRF) completion guidelines.
6.2.5.
Excluded Medications
Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to 
leukapheresis and 5 days prior to anti-CD19 CAR T cells administration unless used for bridging 
therapy (refer to Section 6.3.2).  
Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months after 
anti-CD19 CAR T cells administration unless used to manage anti-CD19 CAR T cell related 
toxicities (refer to Section 6.4).  Other medications that may interfere with evaluation of the IP, 
such as non-steroidal anti-inflammatory agents, should also be avoided for the same time period 
unless medically necessary.  
Treatment for the subject’s lymphoma, such as chemotherapy, immunotherapy, targeted agents, 
radiation, and high dose corticosteroid, other than defined/allowed in this protocol, and other 
investigational agents are prohibited except as needed for treatment of disease progression after 
anti-CD19 CAR T cells infusion.  If permissibility of a specific medication/treatment is in 
question, contact the Kite medical monitor.
6.2.6.
Subsequent Therapy 
Subsequent therapy, such as non-study specified chemotherapy, immunotherapy, targeted agents, 
SCT, or radiation therapy, administered after anti-CD19 CAR T-cell infusion that is necessary to 
treat a subject’s disease will be recorded for all subjects until one of the following happens: the 
subject transitions to the KT-US-982-5968 LTFU study, is considered lost to follow-up, 
withdraws consent, or dies.
For subjects who are enrolled but do not receive an anti-CD19 CAR T-cell infusion, any 
additional anticancer therapy will also be collected until the subject completes their participation 
in the current study (refer to Section 3.5.2), is considered lost to follow-up, withdraws consent, 
or dies, whichever occurs first.
6.3.
Study Treatment Schedule
6.3.1.
Leukapheresis (Within Approximately 5 Days of Eligibility Confirmation)
Subjects will undergo leukapheresis to obtain leukocytes (white blood cells [WBCs]) for the 
manufacturing of KTE-X19 or axicabtagene ciloleucel.  Leukapheresed cells obtained at 
participating centers will be shipped to the cell processing facility (CPF) overnight as described 
in the Investigational Product Manual.    


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Mononuclear cells will be obtained by leukapheresis 
 
.  The leukapheresed cells are then packaged for 
expedited shipment to the CPF as described in the Investigational Product Manual.    
Upon arrival at the CPF, each subject’s leukapheresed product will be processed to enrich for the 
T cell containing PBMC fraction.  T cells are then stimulated to expand and transduced with a 
retroviral vector to introduce the CAR gene.  The T cells are then expanded and cryopreserved to 
generate the IP per CPF standard operating procedures (SOPs).  After the product has passed 
certain release tests, it will be shipped back to the treating facility.  Following completion of each 
subject’s conditioning chemotherapy regimen, subjects will receive their respective KTE-X19 or 
axicabtagene ciloleucel infusion.  
6.3.2.
Bridging Therapy  
6.3.2.1.
Cohort 1 and Cohort 2
At the discretion of the investigator and after discussion with the medical monitor, bridging 
therapy may be considered for any subject, particularly those with high disease burden at 
screening (eg, > 25% marrow involvement and/or ≥ 1,000 leukemic phase mantle cells/mm3 in 
the peripheral circulation).  
Bridging therapy is to be administered after leukapheresis and must be completed at least 5 days 
prior to initiating conditioning chemotherapy.  
In Cohort 1 and Cohort 2, bridging therapy is allowed with (1) dexamethasone at a dose of 20 to 
40 mg or equivalent, either PO or IV daily for 1 to 4 days, (2) ibrutinib at a dose of 560 mg PO 
daily or most recent dose if there had been a dose adjustment, or (3) acalabrutinib 100 mg PO 
every 12 hours or most recent dose if there had been a dose adjustment.  Choice of corticosteroid 
and dose can be adjusted for age/comorbidities or per local or institutional guidelines.
If bridging therapy is administered, the subject must undergo another PET-CT or diagnostic CT 
to assess disease status prior to receiving conditioning chemotherapy and subsequent anti-CD19 
CAR T-cell infusion (refer to Section 7.8 for detailed timing and imaging requirements).
6.3.2.2.
Cohort 3
At the discretion of the investigator and per institutional guidelines and standard of care and after 
discussion with the medical monitor, bridging therapy is recommended for all subjects, 
particularly those with rapidly progressing disease, clinical deterioration, or high disease burden 
at screening (eg, > 25% marrow involvement and/or ≥ 1,000 leukemic phase mantle cells/mm3 in 
the peripheral circulation).
If prescribed, bridging therapy must be administered after leukapheresis and must be completed 
at least 7 days or 5 half-lives, whichever is shorter, prior to initiating conditioning chemotherapy.
Bridging regimen options for Cohort 3 are described in Section 6.2.1.2.
CCI


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If bridging therapy is administered, the subject must undergo another PET-CT or diagnostic CT 
to assess disease status prior to receiving conditioning chemotherapy and subsequent anti-CD19 
CAR T-cell infusion (refer to Section 7.8 for detailed timing and imaging requirements).
6.3.3.
Cyclophosphamide and Fludarabine (Days –5 Through –3 Before Infusion of 
anti-CD19 CAR T cells)
Subjects will receive a non-myeloablative conditioning regimen consisting of cyclophosphamide 
and fludarabine to induce lymphocyte depletion and create an optimal environment for expansion 
of anti-CD19 CAR T cells in vivo. Subjects will initiate conditioning chemotherapy with 
cyclophosphamide and fludarabine beginning on Day –5 through Day –3 with 2 rest days before 
the receiving anti-CD19 CAR T cells.  The 3-day conditioning chemotherapy regimen will be 
administered in an outpatient setting. 
The 3-day conditioning regimen of fludarabine and cyclophosphamide is described below.  
Hydration for cyclophosphamide may alternatively be performed according to local institutional 
guidelines.

IV hydration with 1 L of 0.9% NaCl given prior to cyclophosphamide on the day of infusion

Cyclophosphamide 500 mg/m2 IV over approximately 60 minutes

Fludarabine 30 mg/m2 IV over approximately 30 minutes

An additional 1 L of 0.9% NaCl at the completion of the cyclophosphamide infusion 

Add mesna per institutional guidelines 
Subjects should be instructed to drink plenty of liquids during and for 24 hours following the 
chemotherapy (approximately 2 liters/24 hours).  In general, subjects should be kept well - 
hydrated, but closely monitored, to prevent fluid overload.  Another balanced crystalloid solution 
(such as Ringer’s lactate) can be used in place of 0.9% NaCl if deemed more appropriate in the 
investigator’s opinion.
6.3.3.1.
Dosing Rationale
Administration of conditioning chemotherapy correlates with clinical responses to adoptive cell 
therapy {Dudley 2008}.  Specifically, there appears to be a link between adequate 
lymphodepletion and adoptively-transferred T-cell expansion and function.  The depth and 
duration of the lymphodepletion in pre-clinical models correlate with the anti-tumor activity of 
the adoptively-transferred, tumor-specific CD8+ T cells {Gattinoni 2005}.  Lymphodepletion 
may function by eradicating cytokine sinks for the transferred cells, eliminating regulatory T- 
cells, or enhancing the activation of antigen-presenting cells {Klebanoff 2005}.  Combined 
treatment with cyclophosphamide and fludarabine represents a potent lymphodepleting regimen.  
The ZUMA-1 study of axicabtagene ciloleucel in aggressive large B-cell lymphoma used the 
same cyclophosphamide/fludarabine conditioning regimen that is being used in the ZUMA-2 
study {YESCARTA 2017}.  This regimen was tolerated prior to infusion of the cellular product 
and resulted in a favorable risk‑benefit profile.  Similar doses of cyclophosphamide and 
fludarabine have been administered to subjects with B-cell malignancies prior to anti-CD19 CAR 


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T-cell infusion (NCI Protocol 09‑C‑0082) {Kochenderfer 2016} and were shown to increase 
levels of cytokines known to support T-cell expansion and survival {Kochenderfer 2017a}.  This 
treatment combination was also used as a reduced non-myeloablative conditioning regimen for 
patients with B-cell malignancies who were undergoing alloSCT and resulted in tolerable 
toxicities {Khouri 1998}.
6.3.4.
KTE-X19 or axicabtagene ciloleucel (Day 0, after Fludarabine and 
Cyclophosphamide)
All subjects will be hospitalized to receive treatment with KTE-X19 or axicabtagene ciloleucel 
followed by an observation period of at least 7 days unless otherwise required by country 
regulatory agencies (refer to Section 18.3). 
The following pre anti-CD19 CAR T cells infusion medications should be administered 
approximately 1 hour prior to infusion.  Alternatives to the recommendations below should be 
discussed with the Kite medical monitor.

Acetaminophen 650 mg PO (500 mg to 1000 mg in EU)

Diphenhydramine 12.5 mg to 25 mg IV or 25 mg PO or other antihistamine used as per local 
institution 
Subjects in Cohort 1 and Cohort 3 will receive anti-CD19 CAR T-cell treatment consisting of a 
single infusion of CAR-transduced autologous T cells administered IV at a target dose of 
2 x 106 anti-CD19 CAR T cells/kg.  A minimum dose of 1 x 106 anti-CD19 CAR T cells/kg may 
be administered for subjects in Cohort 1 and Cohort 3.  Subjects in Cohort 2 will receive 
KTE-X19 treatment consisting of a single infusion of CAR-transduced autologous T cells 
administered IV at a target dose of 0.5 x 106 anti-CD19 CAR T cells/kg.  For subjects weighing 
> 100 kg, a maximum flat dose of 2 x 108 anti-CD19 CAR T cells will be administered for 
Cohort 1 and Cohort 3 or 0.5 x 108 anti-CD19 CAR T cells for Cohort 2.  Refer to the 
Investigational Product Manual for all details surrounding the dosing of anti-CD19 CAR T cells.
Subjects will remain in the hospital through Day 7 after treatment with anti-CD19 CAR T cells 
unless otherwise required by country regulatory agencies (refer to Section 18.3).  Subjects should 
not be discharged from the hospital until all anti-CD19 CAR T cells-related non-hematological 
toxicities return to Grade ≤ 1 or return to baseline.  Subjects may be discharged with non-critical 
and clinically stable or slowly improving toxicities (eg, renal insufficiency) even if > Grade 1, if 
deemed appropriate by the investigator.  Subjects should remain hospitalized for ongoing 
anti-CD19 CAR T cells-related fever, hypotension, hypoxia, or ongoing central neurological 
toxicity > Grade 1, or if deemed necessary by the treating investigator. 
6.4.
Toxicity Management
To date, the following important risks have been identified with KTE-X19 and axicabtagene 
ciloleucel: CRS, neurologic toxicity, infections, and cytopenias.  Refer to Section 6 of the current 
IB for details regarding these events and management guidance.


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As the safety experience with KTE-X19 increases, the management guidance may be updated.  
Therefore, it is important that you always refer to the most current version of the KTE-X19 IB 
for guidance regarding managing KTE-X19 related toxicities.
Additional information and management recommendations can also be found in the IB regarding 
important potential risks associated with KTE-X19, as well as possible complications associated 
with malignancy and cancer treatment.


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7.
STUDY PROCEDURES
Research staff should refer to the SOAs (Cohort 1 and Cohort 2: Table 7 and Table 8; Cohort 3: 
Table 9 and Table 10) for an outline of the procedures required.  The visit schedule is calculated 
from anti-CD19 CAR T cells infusion on Day 0. 
An overview of study assessments/procedures is outlined below.  A description for each period 
of the study is provided in Section 7.12.  Refer to the CRF completion guidelines for data 
collection requirements and documentation of study procedures.
7.1.
Informed Consent
Before a subject’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequate explanation of the study design, 
anticipated benefits, and the potential risks.  Subjects should sign the most current IRB/IEC 
approved ICF prior to any study-specific activity or procedure is performed.
The consent process and the subject’s agreement or refusal to participate in the study is to be 
documented in the subject’s medical records.  If the subject agrees to participate, the ICF is to be 
signed and personally dated by the subject and by the person who conducted the informed 
consent discussion.  The original signed ICF will be retained in accordance with institution 
policy and IRB/IEC requirements with a copy of the ICF provided to the subject. 
All subjects who are enrolled into the study should be re-consented with any updated version of 
the IRB/IEC approved ICF if relevant to their participation in the study.
7.2.
Demographic Data
Demographic data will be collected to include sex, age, race, ethnicity, and country of enrollment 
to study their possible association with subject safety and treatment effectiveness.
7.3.
Medical and Treatment History
Relevant medical history prior to the start of AE reporting will be collected.  Relevant medical 
history is defined as data on the subject’s concurrent medical condition that would be typically 
shared in a referral letter.  All findings will be recorded in the CRFs.
In addition to the medical history, all history related to the subject’s disease, treatment, and 
response to treatment will be collected and must date back to the original diagnosis. Subjects in 
Cohort 3 will have disease staging at study entry performed per the Lugano Classification 
{Cheson 2014} (refer to Section 18.2).
For subjects who are being referred from another clinic or institution to the participating research 
center, copies from the subject’s chart should be obtained.


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7.4.
Physical Exam, Vital Signs, Performance Status, and PROs
Physical exams will be performed during screening and at times noted in the SOA.  Changes 
noted in subsequent exams when compared to the baseline exam will be reported as an AE. 
During IP administration/hospitalization, vital signs, including blood pressure, heart rate, oxygen 
saturation, and temperature, will be monitored before and after the anti-CD19 CAR T cells 
infusion and then routinely (every 4 to 6 hours) while hospitalized.  If the subject has a fever 
(temperature 38.3°C or greater) at any time during hospitalization, vital signs will be monitored 
more frequently as clinically indicated.
Performance status as measured by the ECOG scale and will be performed to quantify the 
subject’s general well-being and ability to perform activities of daily life.
7.4.1.
PROs
7.4.1.1.
EQ-5D
The EQ-5D will be completed by all subjects, prior to any other assessment (excluding blood 
draws and imaging), at the screening visit and at other times noted in the SOA.  Subjects who are 
blind or illiterate may have the EQ-5D questions read to them by the study staff.  The study staff, 
however, cannot interpret any of the questions for the subject.  A subject may be exempt from 
completing the questionnaire if he or she is unable to read the questionnaire in one of the country 
languages available.
The EQ-5D is a 2-page generic patient questionnaire for assessing the overall health status of a 
subject.  The EQ-5D consists of a 5-dimension descriptive system, including questions on 
mobility, self-care, usual activities, pain/comfort, and anxiety/depression, and a visual analogue 
scale (VAS) that allows the respondent to record health on a vertical scale (eg, best health to 
worst health), thus allowing a quantitative measure of health outcome.  
7.4.1.2.
EORTC-QLQ-C30 (Cohort 3 Only)
For subjects in Cohort 3 only, the EORTC-QLQ-C30 will be completed by the subject, prior to 
any other assessment (excluding blood draws and imaging), at the screening visit and at other 
times noted in the SOA.
This measure provides a multidimensional assessment of health-related quality of life (HRQoL). 
The EORTC-QLQ-C30 version 3.0 includes the following content: 

5 multi-item functional scales (physical functioning, role functioning, emotional functioning, 
cognitive functioning, social functioning) 

3 multi-item symptom scales (fatigue, nausea and vomiting, pain) 

6 single-item symptom scales (dyspnea, insomnia, appetite loss, constipation, diarrhea, 
financial difficulties) 

1 global health status/quality of life (QoL) scale 


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Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional 
scales and for the global health status/QoL scale indicate a higher level of functioning and a 
better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.  
This instrument does not sum together all items, which can potentially group differences and 
allows an assessment of change across the 15 different domains. In its current version 
(version 3), the questionnaire takes approximately 11 minutes to complete.
7.5.
Neurological Assessment
7.5.1.
Cohort 1 and Cohort 2
For subjects in Cohort 1 and Cohort 2, neurological assessments will be standardized by using 
the Mini-Mental State Examination (MMSE) standard version 2.0.  The MMSE is a 5 to 
10 minute, 11-question measure that examines various areas of cognitive function:  orientation, 
attention, immediate recall, short-term recall, language, and the ability to follow simple verbal 
and written commands.
The MMSE is divided into 2 sections.  The first part requires vocal responses to the examiner’s 
questions.  In the second part of the exam, the subject is asked to follow verbal and written 
instructions, write a sentence spontaneously, and copy a geometric figure. 
A full neurological assessment will be completed during screening to establish a baseline.  For 
subjects enrolled in Cohort 1, subsequent post-baseline assessments will be performed before 
anti-CD19 CAR T cells administration on Day 0, Day 1, Day 3, Day 5, Day 7, and every other 
day while hospitalized, as well as on Day 28 and Month 3.  For subjects enrolled in Cohort 2, a 
subsequent post-baseline assessment will be performed on Day 28.  If the assessment shows 
neurologic function has not returned to baseline (± 3 points) on Day 28, then the MMSE will 
continue to be performed at Month 3 and every 3 months until the results have returned to 
baseline (± 3 points) or until Month 24. 
Every attempt should be made to dedicate a single research staff member familiar with or trained 
in the administration of the MMSE to conduct the assessment to minimize inter-rater variability.  
If CNS symptoms persist, continue to perform the MMSE every 2 days until resolution of 
symptoms or discharged from the hospital.
The severity of neurologic events in Cohort 1 and Cohort 2 will be graded using the NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as described in 
Section 9.2.1.
7.5.2.
Cohort 3
For subjects in Cohort 3, neurological assessments, including an immune effector cell-associated 
encephalopathy (ICE) cognition assessment (Table 17), will be performed according to the time 
points specified in the SOA. 


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The subject’s neurological status will be evaluated at screening to establish a baseline. A 
subsequent postbaseline assessment will be performed at Week 4. If the ICE assessment has not 
returned to baseline (± 1 point) at Week 4, then the assessment will continue to be performed at 
Month 3 and every 3 months until the results have returned to baseline (± 1 point) or until 
Month 24.
The severity of neurologic events in Cohort 3 will be graded using CTCAE version 4.03 and the 
American Society for Transplantation and Cellular Therapy (ASTCT) ICANS consensus grading 
system as described in Section 9.2.1.
For subjects who are hospitalized with neurologic events of Grade 2 or higher, grading should be 
continued daily during any period of Grade 2 or higher neurologic events until symptoms return 
to baseline. Changes in neurological status should be reported as an AE if considered clinically 
significant at the discretion of the investigator.
7.6.
Bone Marrow Assessment
A bone marrow aspirate or biopsy will be performed at screening, if there is a prior history or 
suspicion of bone marrow involvement and not previously performed within 4 weeks of signing 
consent. The bone marrow aspirate or biopsy will be assessed and confirmed for the presence of 
MCL. 
Subjects with a positive bone marrow at screening or those who do not have a baseline bone 
marrow aspirate or biopsy available must undergo another bone marrow aspirate or biopsy upon 
first determination of a CR via PET. Subjects with a negative bone marrow aspirate or biopsy 
(ie- no MCL) at screening, and patients with a partial metabolic response, stable disease (SD) or 
PD at any disease response assessment time point do not require a follow-up bone marrow 
aspirate or biopsy (Figure 3).
For subjects in Cohort 3 only, if collected at screening, bone marrow aspirate or biopsy should 
also be submitted to the central laboratory as formalin-fixed paraffin-embedded (FFPE) block(s) 
or slides for minimal residual disease (MRD) analysis. 


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Figure 3. 
Bone Marrow Assessment Schema 
Screening BM 
Biopsy 
I 
l 
l 
Not Done 
Done within 1 month before ICF or 
anytime during the Screening period 
l 
I 
! 
! 
Positive for Mantle Cell 
Negative for Mantle 
Must repeat BM biopsy to 
Lymphoma 
Cell Lymphoma 
confirm CR irrespective of 
I 
l 
PET-CT findings upon 
response assessment 
' 
No need to repeat BM 
biopsy to confirm CR 
Abbreviations: BM, bone ma1ww; CR, complete response; ICF, informed consent form; PET-CT, positron emission tomography-
computed tomography; 
To confnm a CR, the bone man ow aspirate or biopsy must show no evidence of disease by 
morphology or, if indete1minate by morphology, it must be negative by immunohistochemistiy. 
After CR is confnmed by bone manow aspirate or biopsy, additional bone maiTow aspirates or 
biopsies are only required in case of clinical suspicion of disease progression in the bone maiTow 
only. Refer to Section 7.8, Section 18.1 (Coho1i 1), and Section 18.2 (Coho1i 2 and Coho1i 3) for 
ti·eatment response assessment requirements per the revised International Working Group (IWG) 
Response Criteria for Malignant Lymphoma {Cheson 2007} and Lugano Classification {Cheson 
2014}. 
Bone maiTow aspirate or biopsy should also be considered to evaluate hemophagocytic 
lymphohistiocytosis (HLH) as indicated (refer to the cmTent IB). A po1iion of the bone man ow 
sample collected to evaluate HLH or other toxicities should be subinitted to the centi·al 
laborato1y as outlined in the centi-al laborato1y manual. 
7.7. 
Lumbar Puncture 
Subjects with symptoms of CNS malignancy, such as new onset severe headaches, neck 
stiffness, or any focal neurologic findings on physical exam, will have lumbar puncture 
perfo1med at the screening visit for examination of CSF. In addition, lumbai· punctme should be 
perfo1med as applicable for subjects with new onset of~ Grade 2 nemologic toxicities after 
anti-CD19 CART cells infusion (refer to the cmTent IB). Adequate platelet suppo1i should be 
provided prior to perfonning a lumbar puncture ( eg, platelet > 50,000/mm3). 
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7.8. 
Disease Response Assessment 
Subjects will be evaluated for disease response by the site investigator at times indicated in the 
SOA. For subjects enrolled in Coho1i 1, disease assessments will be evaluated per the revised 
IWG Response Criteria for Malignant Lymphoma as described in Section 18.1 {Cheson 2007}. 
Flow cytometric, molecular, or cytogenetic studies will not be used to detennine response. For 
subjects emolled in Coho1i 2 and Coho1i 3, disease assessments by the site investigator will be 
evaluated per the Lugano Classification, as described in Section 18 .2 { Cheson 2014}. 
Baseline PET-CT scans of the neck, chest, abdomen, and pelvis, along with the appropriate 
imaging of all other sites of disease, are required. PET-CT perfo1med following the subject's last 
line of therapy and prior to signing the consent may be used for confmnation of eligibility. 
PET-CT should be perfo1med as close to enrollment as possible. If PET-CT will be older 
than 28 days at the initiation of conditioning chemotherapy or if the subject receives any 
bridging therapy between the last PET-CT and conditioning chemotherapy, PET-CT must be 
repeated prior to the initiation of conditioning chemotherapy to establish a new baseline. 
However, if the subject receives bridging therapy and the original PET-CT scan is within 28 days 
of the initiation of conditioning chemotherapy, only the diagnostic CT po1iion of the scan needs 
to be repeated prior to the initiation of conditioning chemotherapy. 
Subjects will have their first post anti-CD19 CART cells infusion planned PET-CT tumor 
assessment 4 weeks following the anti-CD19 CAR T cells infusion and at regular intervals as 
highlighted in the SOA during the post-treatment and LTFU po1iion of the study. 
Post anti-CD19 CAR T cells administration disease assessments will be used to detennine the 
time when PD occurs. Subjects with symptoms suggestive of disease progression should be 
evaluated for progression at the time symptoms occur even if it is off schedule as per the SOA. 
A bone manow aspirate or biopsy will be perfo1med in subjects who are being assessed for CR, 
as described in Section 18.1 (Coho1i 1) and Section 18.2 (Coho1i 2 and Cohort 3). Per the 
revised IWG Response Criteria for Malignant Lymphoma {Cheson 2007} and Lugano 
Classification { Cheson 2014}, a bone maITow aspirate or biopsy must be perfo1med when the 
subject had bone maITow involvement with lymphoma prior to therapy or if new abno1malities in 
the peripheral blood counts or blood smear cause clinical suspicion of bone manow involvement 
with lymphoma after treatment. Furthe1more, if bone marrow involvement before the staii of the 
study was unknown, a bone maITow evaluation must be conducted to confirm a CR. The bone 
manow aspirate or biopsy must show no evidence of disease by mmphology or if indete1minate 
by morphology, it must be negative by immunohistochemistiy to assign a CR to treatment. 
In addition to the investigator's assessment, Independent Radiology Review Committee (IRRC) 
review per Lugano Classification { Cheson 2014} will be perfo1med for all coho1is. PET-CT 
scans of all subjects evaluated for disease response will be subinitted to and reviewed by an 
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independent central reviewer.  For subjects who discontinue the study due to an assessment of 
PD, any additional imaging data, subsequent to the image in question, will be submitted to the 
central reviewer to confirm disease status. 
If the subject is eligible for retreatment with KTE-X19, the last scan prior to retreatment will be 
considered the baseline for the purpose of evaluating the response to retreatment.
Requirements for acquisition of PET-CT scans and submission requirements will be outlined in 
the study imaging manual.
7.9.
Cardiac Function 
Each subject’s cardiac function as measured by ECHO will be assessed during the screening 
period to confirm study eligibility.  Both left ventricular ejection fraction (LVEF) and pericardial 
effusion will be assessed prior to study entrance by ECHO.  An ECHO performed following the 
subject’s last chemotherapy treatment and within 28 days prior to signing the consent may be 
used for confirmation of eligibility. For subjects in Cohort 3, a MUGA scan may be used in place 
of ECHO.
To establish a baseline, an ECG will also be performed during screening. 
7.10.
Brain MRI
Each subject will undergo a screening brain MRI, with contrast whenever possible or without 
contrast in case of contraindication, to rule out CNS metastasis during the screening period of the 
study. For subjects in Cohort 3, a brain MRI performed within 28 days prior to signing the 
consent is also acceptable.
Evaluation of any new onset of ≥ Grade 2 neurologic toxicity should include a brain MRI as 
described in the current IB.
For subjects in Cohort 3 with a contraindication for MRI, a CT scan of the brain may be used but 
must include contrast.
7.11.
Laboratory
The below samples will be collected at the time points indicated in the SOA.  Additional samples 
(eg, blood, urine, CSF, tissue) may be collected as needed for further safety testing.

Local lab analysis: 
Chemistry panel: sodium, potassium, chloride, total bicarbonate, creatinine, glucose, 
blood urea nitrogen or urea (if blood urea nitrogen test cannot be analyzed by the local 
lab), albumin, calcium total, magnesium total, inorganic phosphorus, alkaline 
phosphatase, ALT/glutamic-pyruvic transaminase (GPT), AST/glutamic-oxaloacetic 
transaminase (GOT), total bilirubin, direct bilirubin, uric acid
C-reactive protein (CRP) 
LDH


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Ferritin
Complete blood count (CBC) with differential (for clinical/safety evaluation)
A urine or serum sample will be collected and assessed locally for females of childbearing 
potential.  If the screening pregnancy test is positive, the subjects should not be enrolled.  If a 
standard of care pregnancy test is collected during the course of the study and the result is 
positive, the investigator should contact the Kite medical monitor for instructions.  If a female 
partner of a male subject becomes pregnant during the conduct of the study, it must be reported 
by contacting Kite medical monitor for instructions.
For EU sites, a serology (eg, HIV, hepatitis B, hepatitis C, syphilis) test will be carried out per 
institutional guidelines and EU regulations.  This may be within the 30 days prior to 
leukapheresis and/or on the day of leukapheresis.

Central lab analysis:
Blood draws for CBC with differential will be collected and sent to the central laboratory 
for pharmacokinetic assessments at the time points specified in the SOA. Note that these 
samples are distinct from samples collected and sent to the local laboratory for 
assessment of CBC with differential for clinical/safety evaluation.
Blood draws for PBMC (including the analysis of lymphocyte subsets, anti-CD19 CAR 
T cells, and RCR) and cytokine analysis will be performed at intervals outlined in the 
SOA.  
■
Cohort 1 and Cohort 2: After Month 24, PBMC samples will only be collected if an 
RCR event is clinically suspected and/or a subject’s PBMC sample tested positive for 
RCR at any time point within the first year. If the latter, samples will continue to be 
collected and tested annually for up to 15 years or as clinically indicated.
■
Cohort 3: 
○
PBMCs for RCR testing will be collected at baseline (before leukapheresis) and at 
Months 3, 6, and 12. Thereafter, samples will only be collected if an RCR event is 
clinically suspected and/or a subject’s PBMC sample tested positive for RCR at 
any time point within the first year. If the latter, samples will continue to be 
collected and tested annually for up to 15 years or as clinically indicated.
○
PBMCs for analysis of lymphocyte subsets and anti-CD19 CAR T cells will 
continue to be collected at the time points specified in the SOA even if PBMCs 
for RCR testing are no longer required to be collected.
■
All cohorts: If a subject dies or develops a new/secondary malignancy during the 
study or follow-up, every effort should be made to collect blood and a biopsy sample 
of the neoplastic tissue or the pertinent autopsy tissue to assay for RCR.


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-
Sernm samples will also be drawn for anti-CD19 CAR antibodies 
■ Coho1i 1 and Coho1i 2: For sernm samples that demonstrate increased anti-CD19 
CAR antibodies at the Month 3 visit over baseline values, attempts should be made to 
obtain and test additional sernm samples approximately eve1y 3 months until the 
antibody levels return to baseline ( or becomes negative) or up to 1 year from the 
completion of treatment, whichever occurs first. 
■ Coho1i 3: Sennn samples for anti-CD19 CAR antibodies are not required after the 
Month 3 visit. 
-
Archived and/or fresh (newly acquired) tumor tissue will be collected as outlined in the 
SO As and per Section 7 .11.1 for 
• 
• 
• 
rognostic 
markers including p53 and Ki-6 
1iainin to 
the tumor immune environment. 
-
CSF and possibly bone man ow samples will also be collected and analyzed at the central 
laborato1y as outlined in the SO As and per Section 7 .11.1. 
-
See central laborato1y manual for details on sample collection, processing, and shipping 
instructions. 
7.11.1. 
Bio markers 
Biomarker analysis will be perfo1med on blood and tumor samples to evaluate 
haim acod amic mai·kers for anti-CD19 CART cells. Prognostic markers 
related to the tumor immune environment may also be eva uate m archived 
and fresh (newly acquired) tumor biopsies. 
The presence, expansion, persistence, and immunophenotype of transduced anti-CD 19 CAR 
T cells will be monitored in the blood by flow cytometiy. Expansion and persistence will also be 
monitored by a CD 19 CAR specific quantitative polymerase chain reaction ( qPCR) assay. 
Levels of sernm c okines will also be evaluated in the blood. 
Unless medically contraindicated, CSF, as well as any additional subject samples (eg, pleural 
fluid), should be collected from subjects who develop~ Grade 2 neurologic toxicity after KTE-
Xl 9 infusion to enable evaluation of inflammato1y cytokines and chemokine levels. As 
applicable, lymphocyte populations residing in the CSF or other additional subject samples may 
also be monitored for the pmpose of understanding the safety profile of KTE-X19. 
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Because anti-CD19 CART cells comprises retrnviral vector transduced T cells, the presence of 
RCR in the blood of treated subjects will be monitored. If a subject dies or develops a 
new/secondaiy malignancy during the study or follow-up, eve1y effo1t should be made to collect 
blood and a biopsy sample of the neoplastic tissue or the pe1tinent autopsy tissue to assay for 
RCR. 
In addition, baseline leukapheresis and final anti-CD19 CAR T cells samples will be banked and 
may be analyzed by immunophenotyping, qPCR, genomic analysis, and/or gene expression 
profiling. Remaining samples may be stored for future explorato1y analysis of immune- or 
disease-related genomic DNA, RNA, or protein markers. 
For subjects who sign the optional po1tion of the consent f01m (and for all subjects with 
accessible tumor at select sites), on-study paired core biopsies of tumor will be perfo1med at 
baseline, during the IP treatment period (see Section 7.12.6.2 and SOA for timing by coho1t), and 
at Month 6 following anti-CD19 CART cells infusion when expansion and tumor infiltration 
with CART cells is expected. (Note: Optional consent for baseline fresh [newly acquired] tumor 
biopsy applies only to subjects in Cohort 1 and Coho1t 2. For subjects in Coho1t 3, a new tumor 
biopsy is requested to be collected and submitted prior to leukapheresis if clinically feasible.) In 
addition, persisting, relapsing, or emerging lesions could also be biopsied to help detennine 
eligibility for retreatment or mechanisms of tumor resistance. Explorato1y analysis of tumor or 
immune cell markers that con elate with response to KTE-X19 or disease prognosis will be executed. 
These samples and any other components from these samples may be stored up to 15 years from 
the date the last subject is dosed to address explorato1y research scientific questions related to the 
treatment or disease under study. Each subject will have the right to have the sample material 
destroyed at any time by contacting the investigator who, in tum, can contact the sponsor. The 
investigator should provide the sponsor the study and subject number so that the sample can be 
located and destroyed. 
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For subjects who withdraw consent, any samples that were not requested to be returned or 
destroyed will remain with the sponsor and any data that may be generated will be entered in the 
study database. 
7.12.
Description of Study Periods
Investigative sites will maintain a log of all screened subjects who were reviewed and evaluated 
for study participation.  Information collected on the screening log should include limited 
information, such as the date of screening, date the subject was enrolled, or the reason for why 
the subject failed screening.
7.12.1.
Screening
The screening period begins on the date the subject signs the IRB/IEC approved ICF and 
continues through enrollment.  Informed consent must be obtained before completion of any 
study-specific procedures.  Procedures that are part of standard of care are not considered 
study-specific procedures and may be performed prior to obtaining consent and used to confirm 
eligibility.  Confirmation of this data must occur within the time allowance as outlined below and 
in the SOA.
After written informed consent has been obtained, subjects will be screened to confirm study 
eligibility and participation.  Only subjects who meet the eligibility criteria listed in Section 5 
and who commence leukapheresis will be enrolled into the study.  If, at any time prior to 
enrollment, the subject fails to meet the eligibility criteria, the subject should be designated as a 
screen failure on the subject screening log with the reasons for failing screening.
The following assessments/procedures are to be completed during the screening period at the 
time points outlined in the SOA:

Demographic data

Medical history (including disease staging at study entry per the Lugano Classification 
{Cheson 2014} for subjects in Cohort 3)

EQ-5D questionnaire (prior to any other assessments/procedures being performed, excluding 
blood draws and imaging)

EORTC-QLQ-C30 (Cohort 3 only; prior to any other assessments/procedures being 
performed, excluding blood draws and imaging)

Physical examination, including height and weight

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature
Subjects with symptoms of CNS malignancy, such as new onset severe headaches, neck 
stiffness, or any focal neurologic findings on physical exam, will have lumbar puncture 
for examination of CSF.

ECOG performance status 


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
Neurological assessment including MMSE (Cohort 1 and Cohort 2) or ICE (Cohort 3)

ECG

LVEF and pericardial effusion assessment by ECHO (or MUGA for subjects in Cohort 3)

Imaging studies
Brain MRI (or CT with contrast for subjects in Cohort 3 with a contraindication for MRI)
Baseline PET-CT of the neck, chest, abdomen, and pelvis
■
PET-CT performed following the subject’s last line of therapy and prior to signing 
the consent may be used for confirmation of eligibility. PET-CT should be performed 
as close to enrollment as possible. Refer to Section 7.8 for detailed timing and 
imaging requirements, including the potential need for repeat baseline scans prior to 
conditioning chemotherapy.

Bone marrow aspirate or biopsy as needed due to prior history or suspicion of bone marrow 
involvement (if not done within 4 weeks prior to screening)
If collected at screening, bone marrow aspirate or biopsy should be submitted to the 
central laboratory as FFPE block(s) or slides for MRD analysis (Cohort 3 only)

Labs 
β-HCG pregnancy test (serum or urine) on all females of childbearing potential
Chemistry panel with CRP
Creatinine clearance (as estimated by Cockcroft Gault)
CBC with differential (local laboratory)

SAE reporting (refer to Section 9 for safety reporting guidelines)

Concomitant therapies documentation and previous cancer treatment history

After eligibility is confirmed, collection of archived tumor sample. For subjects who signed 
the optional portion of the consent, fresh (newly acquired) tumor sample(s) and CSF samples 
may also be provided. 
Note: Optional consent for baseline fresh tumor biopsy applies only to subjects in 
Cohort 1 and Cohort 2. For subjects in Cohort 3, a new tumor biopsy is requested to be 
collected and submitted prior to leukapheresis if clinically feasible. 


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7.12.2.
Rescreening
Subjects who are unable to complete or meet the eligibility criteria during the 28-day screening 
period will be permitted to rescreen one time.  Subjects will retain the same subject ID number 
that was assigned at the original screening.  If rescreening occurs within 28 days of the signing of 
the original informed consent, only the procedure(s)/assessment(s) that did not originally meet 
the eligibility criteria or that become out of window relative to the initiation of conditioning 
chemotherapy (eg, PET-CT scan, blood testing) need to be repeated; all other initial screening 
procedures/assessments do not need to be repeated.  If rescreening occurs > 28 days from the 
signing of the original informed consent or if leukapheresis is delayed > 28 days from the signing 
of the original informed consent, subjects must be reconsented and repeat all screening 
procedures/assessments.
7.12.3.
Enrollment/Leukapheresis
Criteria that must be met before initiating leukapheresis are described in Section 7.12.3.1.1 for 
subjects in Cohort 1 and Cohort 2 and in Section 7.12.3.1.2 for subjects in Cohort 3. Procedures 
to be performed on the leukapheresis collection day for all subjects are described in 
Section 7.12.3.2.
7.12.3.1.
Requirements for Initiating Leukapheresis
7.12.3.1.1.
Cohort 1 and Cohort 2
If any screening assessments or procedures are repeated between confirmation of eligibility and 
the start of leukapheresis and results are outside the eligibility criteria listed in Section 5, contact 
the Kite medical monitor prior to proceeding with leukapheresis.
Before leukapheresis commences, the criteria listed below must be met.  If criteria are not met, 
leukapheresis must be delayed until the event resolves.  If leukapheresis is delayed beyond 
5 days, baseline CBC with differential and chemistry panel must be repeated.  If results are 
outside the eligibility criteria listed in Section 5, contact the Kite medical monitor prior to 
proceeding with leukapheresis. 

No evidence or suspicion of an infection

Corticosteroid therapy at a pharmacologic dose (≥ 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 
7 days prior to leukapheresis.
After a subject commences leukapheresis, the subject will be considered enrolled into the study.   
7.12.3.1.2.
Cohort 3
Leukapheresis is to be performed within approximately 5 days after eligibility confirmation. 
Refer to Section 6.3.1 for a description and definition of leukapheresis. Before leukapheresis 
commences, the following criteria must be met:


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
In general, all criteria that were confirmed during screening for eligibility must not be known 
to be violated before leukapheresis, except that allowance will be made for expected normal 
variation of within 5% of laboratory test value cutoffs noted in the inclusion criteria. 
Additionally, the investigator must review and confirm that the last CBC with differential 
and chemistry panel results from the blood draw before the start of leukapheresis meet the 
criteria detailed in Section 5.1 ± 5%. If any screening assessments or procedures are repeated 
between confirmation of eligibility and the start of leukapheresis and the results are outside 
the criteria listed in Section 5.1 (or within 5% of the laboratory test value cutoffs noted in the 
inclusion criteria), the subject should not be leukapheresed and the Kite medical monitor 
must be consulted. 

Subjects must have no evidence of clinically significant infection before leukapheresis. 
Should a subject have clinically significant infection immediately before leukapheresis, cell 
collection must be delayed until the event resolves.  

If leukapheresis is delayed > 5 days after eligibility confirmation, a CBC with differential 
and chemistry panel must be repeated. If leukapheresis is delayed > 28 days from the signing 
of the original informed consent, subjects must be reconsented and repeat all screening 
procedures/assessments (refer to Section 7.12.2). 

If the WBC count from a sample collected at the time of leukapheresis is > 20,000 cells/µL, 
the Kite medical monitor must be consulted before proceeding with leukapheresis.

Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 
7 days before leukapheresis (refer to Section 6.2.5).
Refer to Section 6.2.5 for medications that are not allowed before leukapheresis occurs.
After a subject commences leukapheresis, the subject will be considered enrolled into the study.
7.12.3.2.
Procedures/Requirements at Leukapheresis
For all subjects, the following procedures/requirements will occur on the leukapheresis collection 
day and as outlined in the SOA:

ECOG performance status (Cohort 3 only)

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Weight

Labs (to be drawn prior to leukapheresis, on the day of or day before leukapheresis unless 
otherwise specified)
β-HCG pregnancy test (serum or urine) on all females of childbearing potential within 
7 days before the initiation of leukapheresis (Cohort 3 only)


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Serology (serum) within 30 days before leukapheresis and/or on the day of leukapheresis 
(EU sites only)
Chemistry panel
CRP; if CRP is ≥ 100 mg/L, a call must be made to the Kite medical monitor before 
proceeding with conditioning chemotherapy.
LDH (Cohort 3 only)
CBC with differential (local and central laboratory)
Cytokine levels 
Anti-CD19 CAR antibodies
Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells) 
Blood draw (plasma) for MRD analysis (Cohort 3 only)

Leukapheresis

AE/SAE reporting 

Concomitant therapies documentation 
7.12.4.
Bridging Therapy 
If prescribed, bridging therapy as described in Section 6.2.1 must be administered after 
leukapheresis and completed at least 5 days prior to initiating conditioning chemotherapy for 
subjects in Cohort 1 and Cohort 2, or at least 7 days or 5 half-lives, whichever is shorter, prior to 
initiating conditioning chemotherapy for subjects in Cohort 3 (refer to Section 6.3.2). If bridging 
therapy is administered, PET-CT or diagnostic CT must be repeated prior to the start of 
conditioning chemotherapy to establish a new baseline (refer to Section 7.8 for detailed timing 
and imaging requirements).  

AE/SAE reporting 

Concomitant therapies documentation 
7.12.5.
Conditioning Chemotherapy Period
If any screening assessments or procedures are repeated between screening and the start of 
conditioning chemotherapy and results are outside the eligibility criteria (Section 5), contact the 
Kite medical monitor for approval prior to proceeding with conditioning chemotherapy.
As described in Section 7.8, if PET-CT will be older than 28 days at the initiation of 
conditioning chemotherapy or if the subject receives any bridging therapy between the last 
PET-CT and conditioning chemotherapy, the PET-CT must be repeated prior to the initiation of 


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conditioning chemotherapy to establish a new baseline. However, if the subject receives bridging 
therapy and the original PET-CT scan is within 28 days of the initiation of conditioning 
chemotherapy, only the diagnostic CT portion of the scan needs to be repeated prior to the 
initiation of conditioning chemotherapy.
7.12.5.1.
Requirements for Initiating Conditioning Chemotherapy 
Administration of anti-CD19 CAR T cells to subjects with ongoing infection or inflammation, 
even if such processes are asymptomatic, increases the risk of high grade and fatal toxicity.  All 
efforts should be made to rule out such conditions prior to both conditioning chemotherapy and 
cell infusion. Signs, symptoms or abnormal laboratory results attributed to the malignancy (eg 
“tumor fever,” elevated CRP) are diagnoses of exclusion that require a documented workup to 
establish. Conditioning chemotherapy and anti-CD19 CAR T cells infusion should only be 
initiated after it is reasonably assured that cell infusion can safely proceed.
If any of the following criteria are met prior to the initiation of conditioning chemotherapy, then 
the workup listed in Section 7.12.7 must be performed to determine the potential cause if there is 
no identified source of infection.  

Temperature > 38°C within 72 hours of conditioning chemotherapy

CRP > 100 mg/L anytime between enrollment to start of conditioning chemotherapy

WBC count or WBC differential, that is suggestive of infectious process, and is observed 
between enrollment and the initiation of conditioning chemotherapy (eg, WBC > 20,000/µL, 
rapidly increasing WBC, or differential with high percentage of segs/bands)
Additionally:

If any screening assessments or procedures are repeated between confirmation of eligibility 
and the start of conditioning chemotherapy and results are outside the eligibility criteria listed 
in Section 5 (or within 5% of the laboratory test value cutoffs noted in the inclusion criteria), 
then the condition must resolve prior to proceeding with conditioning chemotherapy.

Complete history and physical exam, including head, ears, eyes, nose, and throat (HEENT) 
exam; cardiac, vascular, respiratory, gastrointestinal, integumentary, and neurological 
systems must not reveal evidence of infection/inflammation. 

The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within 48 hours before conditioning chemotherapy (prophylactic use of 
antimicrobials is allowed).  

Treatment course of any antimicrobials given for known or suspected antecedent infection 
should be complete as per infectious disease consult (if applicable) recommendation before 
stopping or switching to prophylactic antimicrobials.  


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
If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator and in consultation with infectious disease service (if applicable).

The most recently collected blood, urine, or other body fluid cultures must show no growth 
for at least 48 hours, and any other infectious workup performed (eg, bacterial, viral 
serologies, polymerase chain reaction (PCR), stool studies, imaging studies) must be 
negative.  If clinical suspicion is for an infection for which cultures are unlikely to be 
positive within 48 hours (eg, fungal infection), adequate time must be allowed for cultures to 
become positive.
Once the above criteria are met, then the subject can proceed with conditioning chemotherapy.
7.12.5.2.
Conditioning Chemotherapy Administration 
The following procedures will be completed during Day –5 to Day –3 at the time points outlined 
in the SOA:

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Labs (to be drawn prior to chemotherapy)
β-HCG pregnancy test (serum or urine) on all females of childbearing potential within 
7 days before the initiation of conditioning chemotherapy (Cohort 3 only)
Chemistry panel with CRP
CBC with differential (local laboratory)

Fludarabine and cyclophosphamide administration

AE/SAE reporting 

Concomitant therapies documentation 
7.12.6.
IP Treatment Period
Subjects will be hospitalized to receive treatment with anti-CD19 CAR T cells followed by a 
minimum 7-day observation period unless otherwise required by country regulatory agencies 
(refer to Section 18.3). 
7.12.6.1.
Requirements for Initiating KTE-X19 Infusion
If any of the following criteria are met prior to the initiation of KTE-X19 infusion, then the 
workup listed in Section 7.12.7 must be performed to determine the potential cause if there is no 
identified source of infection.  

Temperature > 38°C within 72 hours of KTE-X19 infusion

CRP > 100 mg/L anytime between enrollment to start of KTE-X19 infusion 


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
WBC count or WBC differential, which is suggestive of infectious process, and is observed 
between enrollment and the initiation of KTE-X19 infusion (eg, WBC > 20,000/µL, rapidly 
increasing WBC, or differential with high percentage of segs/bands)
Additionally:

If any screening assessments or procedures are repeated between confirmation of eligibility 
and the start of KTE-X19 infusion and results are outside the eligibility criteria listed in 
Section 5 (or within 5% of the laboratory test value cutoffs noted in the inclusion criteria), 
then the condition must resolve prior to proceeding with KTE-X19 infusion (except for 
peripheral blood cell counts that have been impacted by conditioning chemotherapy).

Complete history and physical exam, including HEENT exam, cardiac, vascular, respiratory, 
gastrointestinal, integumentary, and neurological systems, must not reveal evidence of 
infection/inflammation. 

The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within 48 hours before KTE-X19 infusion (prophylactic use of 
antimicrobials is allowed).  

Treatment course of any antimicrobials given for known or suspected antecedent infection 
should be complete as per infectious disease consult (if applicable) recommendation before 
stopping or switching to prophylactic antimicrobials.  

If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator in consultation with infectious disease service (if applicable).

Most recently collected blood, urine, or other body fluid cultures must show no growth for at 
least 48 hours, and any other infectious workup performed (eg, bacterial, viral serologies, 
PCR, stool studies, imaging studies) must be negative.  If clinical suspicion is for an infection 
for which cultures are unlikely to be positive within 48 hours (eg, fungal infection), adequate 
time must be allowed for cultures to become positive.
After the above criteria are met, then the subject can proceed with administration of KTE-X19.
If the KTE-X19 infusion is delayed > 2 weeks, protocol guidelines should be followed regarding 
the need for repeat conditioning chemotherapy. 
7.12.6.2.
Hospitalization for KTE-X19 Infusion
Subjects will remain in the hospital through Day 7 after treatment with anti-CD19 CAR T cells 
unless otherwise required by country regulatory agencies (refer to Section 18.3).  Subjects should 
not be discharged from the hospital until all anti-CD19 CAR T cells-related non-hematological 
toxicities return to Grade 1 or return to baseline.  Subjects may be discharged with non-critical 
and clinically stable or slowly improving toxicities (eg, renal insufficiency) even if > Grade 1 if 
deemed appropriate by the investigator.  Subjects should remain hospitalized for ongoing anti-


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CD19 CAR T cells-related fever, hypotension, hypoxia, or ongoing central neurological toxicity 
> Grade 1 or if deemed necessary by the treating investigator. 
Given the possibility that a subject could develop CRS or a neurologic toxicity in the outpatient 
setting after discharge, subjects and their family members/caregivers should be educated on 
potential symptoms of these syndromes such as fever, dyspnea, confusion, aphasia, dysphasia, 
somnolence, encephalopathy, ataxia, or tremor.  If subjects develop these symptoms, they should 
be instructed to immediately contact the principal investigator or seek immediate medical 
attention. 
During this period, the following procedures will be completed at the time points outlined in the 
SOA:

EQ-5D and EORTC-QLQ-C30 (Cohort 3 only; prior to any other assessments/procedures 
being performed, excluding blood draws and imaging)

ECOG performance status (Cohort 3 only)

Neurological assessment including MMSE (Cohort 1)
MMSE will be administered before treatment with anti-CD19 CAR T cells on Day 0, 
then on Day 1, and every other day while hospitalized for subjects enrolled in Cohort 1.  
MMSE will not be administered during the investigational treatment period for subjects 
enrolled in Cohort 2.  

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature, every 
4 to 6 hours during hospitalization

Labs (before anti-CD19 CAR T cells infusion and as described in the SOA)
Chemistry panel
■
If hospitalization continues beyond Day 7 (or as otherwise required by country 
regulatory agencies [Section 18.3]), blood draws for chemistry panel should continue 
to be performed daily during the extended hospitalization. Extended hospitalization 
and post-treatment monitoring will be conducted as medically indicated in EU 
countries and the United Kingdom (UK). 
CRP, ferritin, and LDH
Monitoring of CRP, ferritin, and LDH levels may assist with the diagnosis and define 
the clinical course regarding CRS/neurologic toxicity. CRP, ferritin, and LDH are to 
be monitored daily starting at Day 0 and continuing through hospitalization. If 
hospitalization continues beyond Day 7 (or as otherwise required by country 
regulatory agencies [Section 18.3]), CRP, ferritin, and LDH should continue to be 
monitored daily if levels remain elevated or are uptrending. In addition, lactate should 
be monitored as clinically indicated.


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CBC with differential (local and/or central laboratory)
■
If hospitalization continues beyond Day 7 (or as otherwise required by country 
regulatory agencies [Section 18.3]), blood draws for local laboratory assessment of 
CBC with differential should continue to be performed daily during the extended 
hospitalization. Extended hospitalization and post-treatment monitoring will be 
conducted as medically indicated in EU countries and the UK.
Cytokine levels 
Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells, and RCR 
analysis) 
■
If a subject dies or develops a new/secondary malignancy during the study or 
follow-up, every effort should be made to collect blood and a biopsy sample of the 
neoplastic tissue or the pertinent autopsy tissue to assay for RCR.

Infusion of KTE-X19 or axicabtagene ciloleucel

As applicable, lumbar puncture for subjects with new onset Grade ≥ 2 neurologic symptoms 
after anti-CD19 CAR T cells infusion, or subjects who signed the optional portion of the 
consent should be completed for examination of CSF

Collection of fresh (newly acquired) tumor sample(s) for subjects who signed the optional 
portion of the consent
Cohort 1 and Cohort 2: Tumor sample will be collected anytime between Day +7 and 
Day +14
Cohort 3: Optional tumor sample will be collected on Day 5 ± 2 days

AE/SAE reporting (refer to Section 9 for safety reporting guidelines)

Concomitant therapies documentation 
7.12.7.
Requirements to Work Up Potential Infectious and/or Inflammatory States
In the absence of an identified source of infection (eg, line infection, pneumonia on chest x-ray), 
the minimum workup to be performed prior to administration of conditioning chemotherapy 
and/or KTE-X19 consists of:

Call Kite medical monitor

Infectious Disease service consult (if available)

CT imaging of the chest, abdomen, and pelvis with IV contrast.  If there is a medical 
contraindication to contrast, then non-contrast CT is allowed.  


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
The following must be performed (prior to the initiation of antimicrobials if clinically 
feasible): 
Blood cultures (aerobic and anaerobic x2 bottles each) and urinalysis (UA) and urine 
culture.   Deep/induced sputum culture if clinically indicated.
All indwelling lines such as central venous catheters should be examined for any signs of 
infection and additional cultures should be drawn from the line
Nasopharyngeal-throat swab or equivalent assay for viral infection such as influenza A/B 
(including H1N1), parainfluenza 1/2/3, adenovirus, respiratory syncytial virus, 
coronavirus, metapneumovirus
Collection of fungal cultures and markers as appropriate (eg, galactomannan, Fungitell®)
Collection of appropriate serum viral studies (eg, cytomegalovirus [CMV])

If a CNS process is suspected, appropriate brain imaging and subsequent lumbar puncture 
with cytology, culture, Gram stain, and viral PCR should be performed  

Any additional sign or symptom-directed investigation should be performed as clinically 
indicated
Prior to proceeding with conditioning chemotherapy and/or KTE-X19 infusion, the above 
workup must not suggest the presence of an active infection, and all requirements for 
conditioning chemotherapy and/or KTE-X19 infusion must be satisfied. If the KTE-X19 infusion 
is delayed > 2 weeks following conditioning chemotherapy, protocol guidelines should be 
followed regarding the need for repeat conditioning chemotherapy. 
If the above workup was triggered due to CRP > 100 mg/L, CRP should be repeated. If CRP 
continues to increase significantly, an evaluation should be performed for any other potential 
infectious or inflammatory condition that was not previously evaluated.  
7.12.8.
Post-treatment Assessment Period
After completing anti-CD19 CAR T cells infusion and being discharged from the hospital, all 
subjects will be followed in the post-treatment assessment period.  Counting from Day 0 
(anti-CD19 CAR T cells infusion), subjects will return to the clinic at the following intervals.

Week 2 (± 2 days)

Week 4 (± 3 days)

Month 2 (± 1 week)

Month 3 (± 1 week)


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Subjects will allow key sponsor contacts to continue to access medical records so that 
information related to subjects’ health condition and initial treatment response may be obtained.  
The following procedures will be completed for subjects at the time points outlined in the SOA:

EQ-5D questionnaire (prior to any other assessments/procedures being performed, excluding 
blood draws and imaging) 

EORTC-QLQ-C30 (Cohort 3 only; prior to any other assessments/procedures being 
performed, excluding blood draws and imaging)

Neurological assessment including MMSE (Cohort 1 and Cohort 2) or ICE (Cohort 3)
For subjects enrolled in Cohort 1, the MMSE will be performed on Week 4 and Month 3.  
For subjects enrolled in Cohort 2, the MMSE will be performed on Day 28.  If the 
assessment has not returned to baseline (± 3 points) on Day 28, then continue to perform 
the MMSE at Month 3 and every 3 months until the results have returned to baseline 
(± 3 points) or until Month 24.
For subjects enrolled in Cohort 3, a neurological assessment, including an ICE cognition 
assessment, will be performed at Week 4. If the ICE assessment has not returned to 
baseline (± 1 point) at Week 4, then continue to perform the assessment at Month 3 and 
every 3 months until the results have returned to baseline (± 1 point) or until Month 24.

PET-CT for disease assessment:  If the PET-CT is not of high enough resolution, the scan 
must be repeated.  Refer to the current version of the imaging site manual for detailed 
instructions.

As applicable, bone marrow aspirate or biopsy to confirm CR (ie, for subjects presenting 
with bone marrow involvement prior to therapy, for subjects without a bone marrow aspirate 
or biopsy at baseline, or if new abnormalities in the peripheral blood counts or blood smear 
cause clinical suspicion of bone marrow involvement with lymphoma after treatment)

Physical exam 

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Labs
β-HCG pregnancy test (serum or urine) on all females of childbearing potential
Chemistry panel with CRP
CBC with differential (local and/or central laboratory)
Anti-CD19 CAR antibodies


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Cytokine levels 
Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells, and RCR 
analysis) 
■
If a subject dies or develops a new/secondary malignancy during the study or 
follow-up, every effort should be made to collect blood and a biopsy sample of the 
neoplastic tissue or the pertinent autopsy tissue to assay for RCR.
Blood draw (plasma) for MRD analysis (Cohort 3 only)

AE/SAE reporting (refer to Section 9 for safety reporting guidelines)

Concomitant therapies documentation 
If a subject is discharged from the hospital and is subsequently re-admitted to the hospital with 
any anti-CD19 CAR T cells related AEs, the following procedures will be performed as outlined 
in the SOA:

Anti-CD19 CAR T cell levels on day of admission, then weekly, and on day of discharge

Cytokine levels on day of admission, then weekly, and on day of discharge
At any time during the post-treatment assessment period, if a subject did not respond to treatment 
(ie, did not achieve a CR or PR) or progresses following a response and is either not eligible for 
retreatment or chooses not to pursue retreatment, the subject will proceed directly to the Month 3 
visit and be followed for survival, subsequent therapy, and disease outcomes in the LTFU period.  
A PBMC sample (for anti-CD19 CAR T cells) and serum (for cytokine evaluation) should be 
collected at the time of progression and prior to starting any subsequent anti-cancer therapy.
Upon disease progression, sites are encouraged to collect a tumor biopsy and to submit a portion 
of the tumor tissue to the central laboratory for exploratory biomarker analysis.
If a subject dies or develops a new/secondary malignancy during the study or follow-up, every 
effort should be made to collect blood and a biopsy sample of the neoplastic tissue or the 
pertinent autopsy tissue to assay for RCR.
7.12.9.
LTFU Period
All enrolled subjects will be followed in the LTFU period for survival and disease status, if 
applicable.  Subjects will begin the LTFU period after they have completed the Month 3 visit of 
the post-treatment assessment period (whether they have responded to treatment or went straight 
to the Month 3 visit due to disease progression). 

Every 3 months (± 2 weeks) through Month 18 (for Cohort 1 and Cohort 2) or through 
Month 21 (for Cohort 3)

Month 24 (± 1 month)


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Beginning with Protocol Amendment 8 and after completion of at least 24 months of 
assessments in KTE-C19-102 (refer to Section 3.5.2), subjects who received an infusion of 
anti-CD19 CAR T cells will be given the opportunity to transition to a separate LTFU study, 
KT-US-982-5968, after providing signed informed consent. Before a subject transitions to 
KT-US-982-5968, all assessments will be completed under the ZUMA-2 protocol according to 
the frequency specified in the SOA (Table 8 and Table 10). Upon transition to KT-US-982-5968, 
subsequent assessments will be completed under the KT-US-982-5968 study according to the 
requirements detailed in the KT-US-982-5968 protocol.
The following procedures will be completed for subjects who are enrolled and receive anti-CD19 
CAR T cells at the time points outlined in the SOA:

EQ-5D questionnaire (prior to any other assessments/procedures being performed, excluding 
blood draws and imaging)

EORTC-QLQ-C30 (Cohort 3 only; prior to any other assessments/procedures being 
performed, excluding blood draws and imaging)

Neurological assessment including MMSE (Cohort 2) or ICE (Cohort 3)
For subjects enrolled in Cohort 2, if the MMSE performed on Day 28 and Month 3 had 
not returned to baseline (± 3 points), then continue to perform the MMSE at Month 6 and 
every 3 months until the results have returned to baseline (± 3 points) or until Month 24. 
For subjects enrolled in Cohort 3, if the ICE assessments performed at Week 4 and 
Month 3 had not returned to baseline (± 1 point), then continue to perform the assessment 
at Month 6 and every 3 months until the results have returned to baseline (± 1 point) or 
until Month 24.

Physical exam

PET-CT scan/disease assessment: through 24 months or until disease progression, whichever 
occurs first.  If subject’s disease has not progressed by Month 24, disease assessments will 
continue to be performed per standard of care.

As applicable, bone marrow aspirate or biopsy to confirm CR (ie, for subjects presenting 
with bone marrow involvement prior to therapy, for subjects without a bone marrow aspirate 
or biopsy at baseline, or if new abnormalities in the peripheral blood counts or blood smear 
cause clinical suspicion of bone marrow involvement with lymphoma after treatment)

Survival status

Labs 
CBC with differential (local and/or central laboratory)
Anti-CD19 CAR antibodies (Cohort 1 and Cohort 2 only; refer to Section 7.11)


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Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells, and RCR 
analysis; refer to Section 7.11) 
■
Cohort 1 and Cohort 2: After Month 24, PBMC samples will only be collected if an 
RCR event is clinically suspected and/or a subject’s PBMC sample tested positive for 
RCR at any time point within the first year. If the latter, samples will continue to be 
collected and tested annually for up to 15 years or as clinically indicated.
■
Cohort 3:
○
In the follow-up period, PBMCs for RCR testing will be collected at Months 6 
and 12. Thereafter, samples will only be collected if an RCR event is clinically 
suspected and/or a subject’s PBMC sample tested positive for RCR at any time 
point within the first year. If the latter, samples will continue to be collected and 
tested annually for up to 15 years or as clinically indicated.
○
PBMCs for analysis of lymphocyte subsets and anti-CD19 CAR T cells will 
continue to be collected at the time points specified in the SOA even if PBMCs 
for RCR testing are no longer required to be collected.
■
All cohorts: If a subject dies or develops a new/secondary malignancy during the 
study or follow-up, every effort should be made to collect blood and a biopsy sample 
of the neoplastic tissue or the pertinent autopsy tissue to assay for RCR.
Blood draw (plasma) for MRD analysis (Cohort 3 only)

Targeted AE/SAE reporting (for 15 years or until disease progression or initiation of 
subsequent anticancer therapy, whichever occurs first) (refer to Section 9 for safety reporting 
guidelines)
Any new/secondary malignancy, with the exception of a relapse of the primary 
malignancy, occurring after the administration of KTE-X19 should be reported as an 
SAE for up to 15 years regardless of disease progression.

Targeted concomitant therapies documentation (for 5 years or until disease progression or 
subsequent therapy, whichever comes first)
Including gammaglobulin, immunosuppressive drugs, anti-infective drugs, vaccinations, 
and anticancer therapies 

Subsequent therapy for the treatment of lymphoma

Collection of fresh (newly acquired) tumor sample(s) for subjects who signed the optional 
portion of the consent
Subjects may also be contacted by telephone to confirm survival status and report targeted 
concomitant therapy use. 


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If a subject progresses in the LTFU phase, the subject will continue to be followed for survival 
status, subsequent therapy for the treatment of MCL, and targeted SAE reporting for 
new/secondary malignancies. A PBMC sample (for anti-CD19 CAR T cells) and serum (for 
cytokine evaluation) should be collected at the time of progression and prior to starting any 
subsequent anti-cancer therapy.
Upon disease progression, sites are encouraged to collect a tumor biopsy and to submit a portion 
of the tumor tissue to the central laboratory for exploratory biomarker analysis.
Subjects who are enrolled/leukapheresed, but do not receive anti-CD19 CAR T cells, will be 
followed only until the end of this study and will undergo the following assessments at the time 
points outlined in the SOA:

Subsequent therapy

Survival status – subjects may be contacted by telephone to confirm survival status

Disease assessment per standard of care

AE/SAE reporting and concomitant therapies documentation until 30 days after last 
study-specific procedure (eg, leukapheresis, conditioning chemotherapy) or until initiation of 
a new anticancer therapy, whichever occurs first
If the subject fails to return to the clinic for a scheduled protocol-specific visit, sites will need to 
make 2 attempts by a combination of telephone and mail to contact the subject.  Sites must 
document both attempts to contact the subject.  If a subject does not respond within 1 month after 
the second contact, the subject will be considered lost to follow-up, and no additional contact 
will be required.
Subjects who undergo an alloSCT will be contacted to confirm the status of their disease and 
survival status and will have blood collected for PBMCs per the LTFU schedule.
7.12.10.
Retreatment 
Allowance for retreatment is based on clinical experience reported in the 2 studies conducted at 
the pediatric {Lee 2015} and Surgery Branch {Kochenderfer 2015} of the NCI where 6 subjects 
in total have been retreated upon progression. Three of the retreated subjects (indolent 
lymphoma/leukemia) experienced durable responses to retreatment after an initial response and 
disease progression.
Subjects must meet the criteria for retreatment as listed in Section 7.12.10.2 for Cohort 3. 
Beginning with Protocol Amendment 8, no further retreatment option is available for subjects 
treated in Cohort 1 and Cohort 2.
The decision to administer retreatment should be made in consultation with the Kite medical 
monitor. In addition, a discussion regarding benefits and risks of retreatment, including the 
potential need to undergo leukapheresis a second time for the manufacturing of KTE-X19, 
should occur with the subject prior to performing any study-related procedures or treatment. This 
conversation should also be recorded in the subject’s source documents.  


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A maximum of 1 retreatment course may occur per subject. Subjects who are retreated must 
follow the same treatment schedule and dosing and procedural requirements per the initial 
treatment.
7.12.10.1.
Cohort 1 and Cohort 2
Beginning with Protocol Amendment 8, no further retreatment option is available for 
subjects treated in Cohort 1 and Cohort 2. Prior to Protocol Amendment 8, subjects in 
Cohort 1 and Cohort 2 may have been retreated if they met the criteria listed below.
Subjects who achieved a PR or CR had an option to receive a second course of conditioning 
chemotherapy and KTE-X19 under the following conditions:

Subject had a PR or CR at the Month 3 disease assessment

Subject’s disease subsequently progressed greater than 3 months after axicabtagene 
ciloleucel or KTE-X19 infusion

CD19 tumor expression confirmed locally by biopsy after disease progression and prior to 
retreatment.  A portion of the biopsy should be sent to the central laboratory.

Subject continues to meet the original study eligibility criteria with exception of prior 
axicabtagene ciloleucel or KTE-X19 use in this study.  Screening assessments should be 
repeated if clinically indicated, as determined by the investigator, to confirm eligibility.

Subject has not received subsequent therapy for the treatment of lymphoma.

Subject did not experience a Grade 4 CRS event per Lee 2014 (except for Grade 4 
hematology laboratory events, including pancytopenia, anemia, neutropenia, neutropenic 
fever, leukopenia, and thrombocytopenia) or Grade 4 neurologic toxicity

Toxicities related to conditioning chemotherapy (fludarabine and cyclophosphamide), with 
the exception of alopecia, have resolved to ≤ Grade 1 or returned to baseline prior to 
retreatment.
7.12.10.2.
Cohort 3
Subjects will have an option to receive a second course of conditioning chemotherapy and 
KTE-X19 under the following conditions:

Subject had a PR or CR at the Month 3 disease assessment

Subject’s disease subsequently progressed greater than 3 months after KTE-X19 infusion

Subject received initial KTE-X19 infusion ≤ 24 months ago 

CD19 tumor expression confirmed locally by aspirate or biopsy after disease progression and 
prior to retreatment. When a biopsy is obtained, a portion of the biopsy should be sent to the 
central laboratory. 


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
Subject continues to meet the original study eligibility criteria with exception of prior 
KTE-X19 use in this study. Screening assessments should be repeated if clinically indicated, 
as determined by the investigator, to confirm eligibility.

Subject has not received subsequent therapy for the treatment of lymphoma, except for 
bridging therapy as outlined below

Toxicities related to conditioning chemotherapy (fludarabine and cyclophosphamide), with 
the exception of clinically insignificant toxicities (eg, alopecia), have resolved to severity of 
Grade 1 or lower or returned to baseline prior to retreatment

Subject must not have had a Grade 2 or higher KTE-X19-related immediate hypersensitivity 
reaction 

Subject did not experience Grade 4 CRS, Grade 4 neurologic events, or any grade of edema 
in the brain with the first KTE-X19 infusion

Any CRS and neurologic events have fully resolved before the retreatment
Bridging therapy is recommended for all subjects in Cohort 3 being considered for retreatment, 
particularly those with rapidly progressing disease, clinical deterioration, or high disease burden 
(eg, > 25% marrow involvement and/or ≥ 1,000 leukemic phase mantle cells/mm3 in the 
peripheral circulation) at the discretion of the investigator and per institutional guidelines and 
standard of care and after discussion with the medical monitor.
Bridging therapy (including radiotherapy, corticosteroids, targeted therapy, and chemotherapy) 
will be supplied by the investigative site unless otherwise noted. Sites should refer to the current 
agent-specific product label(s) for guidance on packaging, storage, preparation, administration 
(including necessary dose reductions for organ dysfunction, pregnancy testing requirements, 
etc.), and toxicity management associated with the administration of the agent(s) selected.
In the context of retreatment, bridging therapy must be completed at least 7 days or 5 half-lives, 
whichever is shorter, prior to initiating conditioning chemotherapy.
Bridging regimen options for retreatment in Cohort 3 are listed in Table 6. Retreatment bridging 
regimen should be discussed with the Kite medical monitor. Dose can be adjusted for 
age/comorbidities or per local or institutional guidelines. If radiotherapy is considered for 
retreatment bridging, the radiotherapy modality should be discussed with the Kite medical 
monitor. Radiotherapy should be administered per local or institutional guidelines. Irradiated 
lesions can no longer serve as target lesions, and other target lesions must be present to allow for 
response assessment. Use of any other chemotherapeutic or targeted agent (such as lenalidomide, 
bortezomib, rituximab, venetoclax, and other BTKi) or palliative radiotherapy is to be discussed 
with the Kite medical monitor.


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Clinical Protocol
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Table 6.
Bridging Therapy for Cohort 3 Retreatment
Retreatment Bridging Regimen Options
(1) Corticosteroid
Dexamethasone at a dose of 20 to 40 mg or equivalent, either PO or IV daily for 1 to 
4 days
Choice of corticosteroid and dose can be adjusted for age/comorbidities or per local 
or institutional guidelines
(2) Radiotherapy
Radiotherapy to localized lesions up to 30 Gy in 10 fractions or equivalent
Cytarabine 1 to 2 g/m² IV for a maximum of 2 days
(3) Chemotherapy
Cyclophosphamide 1 to 2 g/m² IV for a maximum of 2 days, or hyperfractionated 
cyclophosphamide 300 mg/m2 administered every 12 hours for 6 doses
(4) Any combination of the following: 1 of the above chemotherapies AND/OR choice of corticosteroid as stated 
above AND/OR radiotherapy to localized lesions as stated above
(5) Ibrutinib 560 mg PO daily (or most recent dose if there had been a dose adjustment) for a maximum of 
14 days, or acalabrutinib 100 mg PO every 12 hours (or most recent dose if there had been a dose adjustment) for 
a maximum of 14 days
Abbreviations: BTKi, Bruton’s tyrosine kinase inhibitor; IV, intravenous; PO, oral.
Note: Use of any other chemotherapeutic or targeted agent (such as lenalidomide, bortezomib, rituximab, venetoclax, and other 
BTKi) or palliative radiotherapy is to be discussed with the Kite medical monitor.


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Clinical Protocol
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7.13.
SOAs
Table 7.
Schedule of Assessments Cohorts 1 & 2 (1 of 2)
Note: All subjects in Cohorts 1 and 2 are in the long-term follow-up period (refer to Table 8); thus, no additional changes will be made 
to this schedule of assessments.
Procedures
Screening
Enrollment/
Leukapheresis
Bridging 
Therapy Period
Conditioning 
Chemotherapy
Period
IP 
Administration 
Period10
Post-treatment Follow-up
(each visit calculated from Day 0)
Day
Within 
28 days of 
enrollment
Within approx. 
5 days of 
eligibility 
confirmation
Completed within 
5 days prior to 
Conditioning 
Chemotherapy
-5
-4
-3
-2
-1
0
1 - 7
Week 2
(± 2 days)
Week 4
(± 3 days)
Month 2
(± 1 week)
Month 3
(± 1 week)
Medical history 
X
ECOG Performance Status
X
EQ-5D Questionnaire
X
X
X
Neurological assessment 
including MMSE6 for 
Cohort 1
X
X
QOD
X
X
Neurological assessment 
including MMSE8 for 
Cohort 2
X
X
X
ECG
X
ECHO
X
Archival/Fresh tumor to 
central lab1
X
Between Day 7 & 
Day 14
Brain MRI
X
PET-CT/ disease assessment2
X
X
X
X
Bone Marrow Assessment9
X
X
X
Physical exam
X
X
X
X
X
Vital signs (BP, HR, O2 sat, 
temp)
X
X
X
X
X
X
X
X
X
X
X
X
Weight (plus height at 
screening)
X
X


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Procedures
Screening
Enrollment/
Leukapheresis
Bridging 
Therapy Period
Conditioning 
Chemotherapy
Period
IP 
Administration 
Period10
Post-treatment Follow-up
(each visit calculated from Day 0)
Day
Within 
28 days of 
enrollment
Within approx. 
5 days of 
eligibility 
confirmation
Completed within 
5 days prior to 
Conditioning 
Chemotherapy
-5
-4
-3
-2
-1
0
1 - 7
Week 2
(± 2 days)
Week 4
(± 3 days)
Month 2
(± 1 week)
Month 3
(± 1 week)
Pregnancy test (serum or 
urine)
X
X
Lumbar Puncture 3
X
X
Blood draw for Chemistry 
panel with CRP
X
X
X
X
X
X
X
X
X
X
X
Blood draw for CBC 
w/differential
X
X
X
X
X
X
X
X
X
X
X
Blood draw for C-reactive 
protein (CRP)
X
X
X
X
X
X
X
X
X
X
X
Blood draw for Anti-CD19 
CAR antibody 4
X
X
X
Blood draw for PBMCs 5, 7
X
X
Day 7
X
X
X
Blood draw for cytokines7
X
X
Day 3 & 7
X
X
Leukapheresis 
X
Bridging Therapy 
(if applicable)
X
Fludarabine/ 
Cyclophosphamide
X
X
X
KTE-X19 infusion IV
X
Adverse events/ 
Concomitant medication
X
Schedule of Assessments Footnotes
Abbreviations: ; AE, adverse event; approx., approximate. BP, blood pressure;  CBC, complete blood count; CAR, chimeric antigen receptor; CRP, C-reactive protein; EQ-5D, 
European Quality of Life-5 Dimensions; ; ECOG, Eastern Cooperative Oncology Group; ECG, electrocardiogram; ECHO, echocardiogram; ; HR, heart rate; IV, intravenous; IP, 
investigational product; MMSE, Mini-Mental Status Exam; MRI, magnetic resonance imaging; NHL, non-Hodgkin lymphoma; PET-CT, positron emission tomography-computed 
tomography; PBMC,  peripheral blood mononuclear cell sat, saturation; SAE, serious adverse event; temp, temperature;
1
Archival tumor sample:  Either FFPE tumor block or up to 20 unstained slides.  Fresh tumor sample for subjects who sign the optional portion of consent; refer to 
Section 7.11.  Archived and fresh tumor samples (if applicable) will be submitted to central laboratory after eligibility has been confirmed and prior to start of conditioning 
chemotherapy.  Post-treatment fresh tumor samples (if applicable) will be collected/submitted anytime between Day 7 and Day 14.  See Section 7.11 and central laboratory 
manual for details.


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2
PET-CT (Neck-Chest-Abdomen-Pelvis)/disease assessment:  If PET-CT performed > 28 days prior to the initiation of conditioning chemotherapy, baseline scans must be repeated.  
Screening PET-CT should be completed as close to enrollment as possible.  A repeat baseline PET-CT is required after bridging therapy and prior to conditioning chemotherapy. 
3
Lumbar Puncture:  Subjects with symptoms of CNS malignancy (eg, new onset severe headaches, neck stiffness, or focal neurological findings) will have lumbar puncture 
performed at screening to assess cerebral spinal fluid for possible CNS involvement.  Subjects with new onset Grade ≥ 2 neurologic symptoms after KTE-X19 infusion will 
have lumber puncture performed to assess cerebral spinal fluid.  In addition, subjects who sign the optional portion of the consent will have lumbar puncture for the collection 
of CSF performed at baseline prior to KTE-X19 infusion and post infusion (Day 5 ± 3 days). 
4
Blood draw for Anti-CD19 CAR antibody:  Baseline antibody sample to be collected prior to start of conditioning chemotherapy.  Anti-CD19 CAR post 3-month samples; see 
Section 7.11.
5
PBMCs:  Blood draw for PBMCs include the analysis of lymphocytes, anti-CD19 CAR T cells, and RCR. If a subject dies or develops a new/secondary malignancy during the 
study or follow-up, every effort should be made to assay for RCR in blood and in a biopsy sample of the neoplastic tissue or the pertinent autopsy tissue.
6
MMSE:  Subjects enrolled in Cohort 1 will have the MMSE assessment at screening, before KTE-X19 administration on Day 0, every other day through hospitalization, 
Day 28, and Month 3.   
7
If subject is subsequently re-admitted to the hospital with any KTE-X19 related adverse events, blood samples for anti-CD19 CAR T cells and cytokines will be collected on 
day of admission, then weekly, and on day of discharge.  Blood samples for anti-CD19 CAR T cells and cytokines should also be collected at the time of disease progression.
8
MMSE:  Subjects enrolled in Cohort 2 will have the MMSE assessments at screening and Day 28.  If the assessment has not returned to baseline (± 3 points) on Day 28, then 
continue to perform the MMSE at Month 3 and every 3 months until the results have returned to baseline (± 3 points) or until Month 24. 
9
Bone Marrow Assessment: Bone marrow aspirate/biopsy as needed (if not done within 4 weeks before screening).  As applicable, bone marrow aspirate/biopsy will be 
performed to confirm complete response (ie, for subjects presenting with bone marrow involvement prior to therapy or if new abnormalities in the peripheral blood counts or 
blood smear cause clinical suspicion of bone marrow involvement with lymphoma after treatment).  Bone marrow samples may also be collected for subjects who develop 
toxicities after KTE-X19 infusion and will be analyzed centrally.  See Section 7.11.  A repeat bone marrow biopsy (if applicable) is required after bridging therapy and prior 
to conditioning chemotherapy. After CR is confirmed by bone marrow biopsy, additional bone marrow biopsies are only required in case of clinical suspicion of disease 
progression in the bone marrow only.
10
Refer to Section 18.3 for requirements by country regulatory agencies. 


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Table 8.
Schedule of Assessments Cohorts 1 & 2 (2 of 2)
Procedure 
Long-term Follow-up Period 12
(Each visit calculated from Day 0)
Visit Frequency
Month 
6 
(± 2w)
Month 
9 
(± 2w)
Month 
12 
(± 2w)
Month 
15 
(± 2w)
Month 
18 
(± 2w)
Month 
24 
(± 1m)12
Month 
30 
(± 1m)
Month 
36 
(± 1m)
Month 
42 
(± 1m)
Month 
48 
(± 1m)
Month 
54 
(± 1m)
Month 
60 
(± 1m)
Month 72 
(± 3m) and 
Annually 
Thereafter 
Up to 
15 Years
EQ-5D Questionnaire
X
Neurological assessment 
including MMSE10 for Cohort 2
X
X
X
X
X
X
Physical exam1
X
X
X
X
X
X
PET-CT Disease Assessment2
X
X
X
X
X
X
X2
X2
X2
X2
X2
X2
X2
Bone Marrow Assessment11
X
X
X
X
X
X
Survival Status
X
X
X
X
X
X
X
X
X
X
X
X
X
CBC w/differential3
X
X
X
X
X
X
Anti-CD19 CAR antibody4
Blood draw for PBMCs5
X
X
X
X
X
X
X5
X5
X5
X5
Targeted AE/SAEs6
X
X
X
X
X
X
X
X
X
X
X
X
X
Targeted concomitant therapies7
X
X
X
X
X
X
X
X
X
X
X
X
Subsequent therapy for MCL8
X
X
X
X
X
X
X
X
X
X
X
X
X
Fresh tumor sample to central 
lab 9
X
Abbreviations: AE, adverse event; CAR, chimeric antigen receptor; CBC, complete blood count; CR, complete response; EQ-5D, European Quality of Life-5 Dimensions; LTFU,  
long-term follow-up; m, month; MCL, mantle cell lymphoma; MMSE, Mini-Mental Status Exam; PBMC, peripheral blood mononuclear cell; PET-CT, positron emission 
tomography-computed tomography; RCR, replication-competent retrovirus; SAE, serious adverse event; w, week.
1
Physical exams will continue through the first 24 months.
2
PET-CT Scans/disease assessments will continue through Month 24 or until disease progression, whichever comes first.  If subject’s disease has not progressed by Month 24, 
disease assessments will continue to be performed per standard of care. 
3
Subjects will continue to provide samples for CBC with differential and lymphocyte subsets through Month 24.
4
Anti-CD19 CAR antibodies post 3-month samples; refer to Section 7.11.


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5
Blood draw for PBMCs include the analysis of lymphocytes, anti-CD19 CAR T cells, and RCR. After Month 24, PBMC samples will only be collected if an RCR event is clinically 
suspected and/or a subject’s PBMC sample tested positive for RCR at any time point within the first year. If the latter, samples will continue to be collected and tested annually for 
up to 15 years or as clinically indicated. If a subject dies or develops a new/secondary malignancy during the study or follow-up, every effort should be made to collect blood and a 
biopsy sample of the neoplastic tissue or the pertinent autopsy tissue to assay for RCR.
6
Targeted AE and SAE reporting will continue for 15 years or until disease progression or initiation of subsequent anticancer therapy (whichever occurs first). Any 
new/secondary malignancy, with the exception of a relapse of the primary malignancy, occurring after the administration of KTE-X19 should be reported as an SAE for up to 
15 years regardless of disease progression. Refer to Section 9.
7
Targeted concomitant therapies documentation will continue for 5 years or until disease progression or subsequent therapy (whichever occurs first).
8
Subsequent therapy administered after KTE-X19 infusion for a subject’s disease, such as non-study specified chemotherapy, immunotherapy, targeted agents, as well as stem 
cell transplant and radiation therapy, must be collected until subject completes the LTFU period, is considered lost to follow-up, withdraws consent, or dies.  Subjects may be 
contacted by telephone to collect information about subsequent therapy for MCL and to assess survival status.
9
Fresh tumor sample for subjects who sign the optional portion of consent; refer to Section 7.11.1.
10
MMSE:  For subjects enrolled in Cohort 2, if the MMSE performed on Day 28 and Month 3 have not returned to baseline (± 3 points), then continue to perform the MMSE at 
Month 6 and every 3 months until the results have returned to baseline (± 3 points) or until Month 24. 
11
Bone Marrow Assessment: As applicable, bone marrow aspirate/biopsy will be performed to confirm complete response (ie, for subjects presenting with bone marrow 
involvement prior to therapy or if new abnormalities in the peripheral blood counts or blood smear cause clinical suspicion of bone marrow involvement with lymphoma after 
treatment).  After CR is confirmed by bone marrow biopsy, additional bone marrow biopsies are only required in case of clinical suspicion of disease progression in the bone 
marrow only.
12
After completion of at least 24 months of assessments in the KTE-C19-102 study, subjects who received an infusion of anti-CD19 CAR T cells will be provided an 
opportunity to transition to the long-term follow-up study (KT-US-982-5968) after providing signed informed consent, to complete the remainder of the 15-year long-term 
follow-up period.


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Clinical Protocol
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Table 9. 
Schedule of Assessments Cohort 3 (1 of 2)
Procedure
Screening
Enrollment/
Leukapheresis
Bridging 
Therapy Period
Conditioning 
Chemotherapy
Period
IP 
Administration 
Period1
Post-treatment Follow-up
(each visit calculated from Day 0)
Day
Within 
28 days of 
enrollment
Within approx. 
5 days of 
eligibility 
confirmation
Completed at 
least 7 days or 
5 half-lives, 
whichever is 
shorter, prior to 
conditioning 
chemotherapy
-5
-4
-3
-2
-1
0
1 – 7
Week 2
(± 2 days)
Week 4
(± 3 days)
Month 2
(± 1 week)
Month 3
(± 1 week)
Demographic data
X
Medical history 
X
Disease staging12
X
ECOG performance status
X
X
X
PROs: EQ-5D and 
EORTC-QLQ-C302
X
X
X
X
Neurological assessment 
including ICE3
X
X
X3
ECG
X
ECHO or MUGA
X
Archival/fresh tumor to 
central lab4
X
Day 5 
± 2 days
Brain MRI13
X
PET-CT/disease assessment5
X
X5
X
X
Bone marrow assessment6
X
X
X
Physical examination
X
X
X
X
X
Vital signs (BP, HR, O2 sat, and 
temp)
X
X
X
X
X
X
X
X
X
X
X
X
Weight (plus height at screening)
X
X
Lumbar puncture7
X
X


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Procedure
Screening
Enrollment/
Leukapheresis
Bridging 
Therapy Period
Conditioning 
Chemotherapy
Period
IP 
Administration 
Period1
Post-treatment Follow-up
(each visit calculated from Day 0)
Day
Within 
28 days of 
enrollment
Within approx. 
5 days of 
eligibility 
confirmation
Completed at 
least 7 days or 
5 half-lives, 
whichever is 
shorter, prior to 
conditioning 
chemotherapy
-5
-4
-3
-2
-1
0
1 – 7
Week 2
(± 2 days)
Week 4
(± 3 days)
Month 2
(± 1 week)
Month 3
(± 1 week)
Local laboratory assessments
Pregnancy test (serum or 
urine)14
X
X14
X14
X
Serology for EU sites (serum)
X15
X15
Blood draw for chemistry 
panel16
X
X
X
X
X
X
X17
X
X
X
X
Creatinine clearance (as 
estimated by Cockcroft Gault)
X
Blood draw for CRP18
X
X
X
X
X
X
X18
X
X
X
X
Blood draw for LDH18
X
X
X18
Blood draw for ferritin18
X
X18
Blood draw for CBC 
with differential (local 
laboratory; for clinical/safety 
evaluation)
X
X
X
X
X
X
X17
X
X
X
X
Central laboratory assessments
Blood draw for CBC with 
differential (central 
laboratory)19
X
X
Day 7
X
X
X
Blood draw for anti-CD19 
CAR antibody8
X
X
Blood draw for PBMCs for 
lymphocyte subsets and 
anti-CD19 CAR T cells10
X
X
Day 7
X
X
X


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Clinical Protocol
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Procedure
Screening
Enrollment/
Leukapheresis
Bridging 
Therapy Period
Conditioning 
Chemotherapy
Period
IP 
Administration 
Period1
Post-treatment Follow-up
(each visit calculated from Day 0)
Day
Within 
28 days of 
enrollment
Within approx. 
5 days of 
eligibility 
confirmation
Completed at 
least 7 days or 
5 half-lives, 
whichever is 
shorter, prior to 
conditioning 
chemotherapy
-5
-4
-3
-2
-1
0
1 – 7
Week 2
(± 2 days)
Week 4
(± 3 days)
Month 2
(± 1 week)
Month 3
(± 1 week)
Blood draw for PBMCs for 
RCR9
X
X
Blood draw (plasma) for MRD 
analysis
X
X
X
Blood draw for cytokines10
X
X
Day 3 & 7
X
X
Leukapheresis 
X
Bridging therapy (if applicable)11
X
Fludarabine/cyclophosphamide
X
X
X
KTE-X19 infusion IV
X
AEs/concomitant therapies
X
Abbreviations: AE, adverse event; approx., approximately; BP, blood pressure; BTKi, Bruton’s tyrosine kinase inhibitor; CAR, chimeric antigen receptor; CBC, complete blood 
count; CNS, central nervous system; CR, complete response; CRP, C-reactive protein; CSF, cerebrospinal fluid; CT, computed tomography; ECG, electrocardiogram; ECHO, 
echocardiogram; ECOG, Eastern Cooperative Oncology Group; EORTC-QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; 
EU, European Union; EQ-5D, European Quality of Life-5 Dimensions; FFPE, formalin-fixed paraffin-embedded; HR, heart rate; ICE, immune effector cell-associated 
encephalopathy; IP, investigational product; IV, intravenous; LDH, lactate dehydrogenase; MRD, minimal residual disease; MRI, magnetic resonance imaging; MUGA, multigated 
acquisition; PBMC, peripheral blood mononuclear cell; PET-CT, positron emission tomography-computed tomography; PRO, patient-reported outcome; RCR, 
replication-competent retrovirus; sat, saturation; temp, temperature.
1
Refer to Section 18.3 for requirements by country regulatory agencies. 
2
PROs: Both PROs will be completed by the subject at the time points specified prior to any other assessment, excluding blood draws and imaging.
3
Neurological assessment: A neurological assessment, including an ICE cognition assessment, will be performed at screening and Week 4. If the ICE assessment has not 
returned to baseline (± 1 point) at Week 4, then continue to perform the assessment at Month 3 and every 3 months until the results have returned to baseline (± 1 point) or 
until Month 24. For subjects who are hospitalized with neurologic events of Grade 2 or higher, grading should be continued daily during any period of Grade 2 or higher 
neurologic events until symptoms return to baseline. See Section 7.5.2 and Section 9.2.1 for details of neurologic event grading and management. 
4
Archival/fresh tumor sample: Submit archival samples at screening as FFPE tumor block(s) or 30 unstained slides. Once archival material is confirmed to be sufficiently 
available at screening, archived samples will be submitted to the central laboratory after eligibility has been confirmed and prior to Day 28. If archival material is unavailable 
or insufficient (< 20 slides), a new tumor biopsy is requested to be scheduled at eligibility confirmation, collected, and submitted prior to leukapheresis if clinically feasible. 
For subjects who sign the optional portion of the consent, a post-treatment fresh (newly acquired) tumor sample will be collected/submitted on Day 5 ± 2 days. See Section 7.11 
and the central laboratory manual for details.


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5
PET-CT (neck-chest-abdomen-pelvis)/disease assessment: Screening PET-CT should be completed as close to enrollment as possible. If PET-CT performed > 28 days prior to 
the initiation of conditioning chemotherapy, baseline scans must be repeated prior to conditioning chemotherapy. For subjects receiving bridging therapy, a repeat baseline 
PET-CT is required after bridging therapy and prior to conditioning chemotherapy; however, if the original PET-CT is within 28 days of the initiation of conditioning 
chemotherapy, only the diagnostic CT portion of the scan needs to be repeated. See Section 7.8 for details. 
6
Bone marrow assessment: Bone marrow aspirate or biopsy will be performed at screening as needed due to prior history or suspicion of bone marrow involvement (if not 
done within 4 weeks before screening). If collected at screening, bone marrow aspirate or biopsy should be submitted to the central laboratory as FFPE block(s) or slides for 
MRD analysis. As applicable, bone marrow aspirate or biopsy will be performed to confirm CR (ie, for subjects presenting with bone marrow involvement prior to therapy, 
for subjects without a bone marrow aspirate or biopsy at baseline, or if new abnormalities in the peripheral blood counts or blood smear cause clinical suspicion of bone 
marrow involvement with lymphoma after treatment). Bone marrow samples may also be collected for subjects who develop toxicities after KTE-X19 infusion and will be 
analyzed centrally. See Section 7.11. After CR is confirmed by bone marrow aspirate or biopsy, additional bone marrow aspirates or biopsies are only required in case of 
clinical suspicion of disease progression in the bone marrow only.
7
Lumbar puncture: Subjects with symptoms of CNS malignancy (eg, new onset severe headaches, neck stiffness, or focal neurological findings) will have lumbar puncture 
performed at screening to assess CSF for possible CNS involvement. Subjects with new onset Grade 2 or higher neurologic symptoms after KTE-X19 infusion will have 
lumbar puncture performed to assess CSF. In addition, subjects who sign the optional portion of the consent will have lumbar puncture for the collection of CSF performed at 
baseline prior to KTE-X19 infusion and after infusion (Day 5 ± 3 days). 
8
Blood draw for anti-CD19 CAR antibody: Baseline antibody sample to be collected prior to start of conditioning chemotherapy.
9
PBMCs for RCR: Samples will be collected at baseline (before leukapheresis) and at Months 3, 6, and 12 (refer to Table 10 for the follow-up period). If a subject dies or 
develops a new/secondary malignancy during the study or follow-up, every effort should be made to collect blood and a biopsy sample of the neoplastic tissue or the pertinent 
autopsy tissue to assay for RCR.
10
If subject is subsequently re-admitted to the hospital with any KTE-X19-related AEs, blood samples for anti-CD19 CAR T cells and cytokines will be collected on day of 
admission, then weekly, and on day of discharge. Blood samples for anti-CD19 CAR T cells and cytokines should also be collected at the time of disease progression.
11
Bridging therapy: Bridging therapy is allowed with (1) dexamethasone or other corticosteroid, (2) palliative radiotherapy to localized lesions, (3) specified chemotherapy, or 
(4) any combination of 1 specified chemotherapy and/or corticosteroid and/or radiotherapy. Bridging regimen should be discussed with the Kite medical monitor, and BTKis 
are not permitted for bridging therapy. See Section 6.2.1.2 for details.
12
Disease staging: Disease staging at study entry will be performed per the Lugano Classification {Cheson 2014} (Section 18.2).
13
A brain MRI performed during the screening period or within 28 days prior to signing the consent is acceptable. For subjects with a contraindication for MRI, a CT scan of 
the brain may be used but must include contrast.
14
Pregnancy test (serum or urine): The test will be completed within 7 days before both leukapheresis and conditioning chemotherapy for females of childbearing potential.
15
Serology for EU sites (serum): Serology tests (ie, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis) will be done per institutional guidelines 
and EU regulations. Testing may be done within the 30 days before leukapheresis/enrollment and/or on the day of leukapheresis/enrollment.
16
Blood draw for chemistry panel: See Section 7.11 for tests to be included in the chemistry panel.
17
If hospitalization continues beyond Day 7 (or as otherwise required by country regulatory agencies [Section 18.3]), blood draws for chemistry panel and local laboratory 
assessment of CBC with differential should continue to be performed daily during the extended hospitalization. Extended hospitalization and post-treatment monitoring will 
be conducted as medically indicated in EU countries and the UK.
18
Blood draw for CRP, ferritin, and LDH: CRP, ferritin, and LDH are to be monitored daily starting at Day 0 and continuing through hospitalization. If hospitalization 
continues beyond Day 7 (or as otherwise required by country regulatory agencies [Section 18.3]), CRP, ferritin, and LDH should continue to be monitored daily if levels 
remain elevated or are uptrending.
19
Blood draw for CBC with differential (central laboratory): At the time points at which PBMC samples are collected for the analysis of lymphocyte subsets and anti-CD19 
CAR T cells, blood samples will also be collected and sent to the central laboratory for assessment of CBC with differential for pharmacokinetic assessments (these samples 
are distinct from samples collected and sent to the local laboratory for assessment of CBC with differential for clinical/safety evaluation).


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Table 10.
Schedule of Assessments Cohort 3 (2 of 2)
Procedure 
LTFU Period12
(Each visit calculated from Day 0)
Visit Frequency
Month 
6 
(± 2w)
Month 
9 
(± 2w)
Month 
12 
(± 2w)
Month 
15 
(± 2w)
Month 
18 
(± 2w)
Month 
21 
(± 2w)
Month 
24 
(± 1m)12
Month 
30 
(± 1m)
Month 
36 
(± 1m)
Month 
42 
(± 1m)
Month 
48 
(± 1m)
Month 
54 
(± 1m)
Month 
60 
(± 1m)
Month 72 
(± 3m) and 
Annually 
Thereafter 
Up to 
15 Years
PROs: EQ-5D and 
EORTC-QLQ-C301
X
X
X
X
X
Neurological assessment 
including ICE2
X
X
X
X
X
X
X
Physical examination3
X
X
X
X
X
X
X
PET-CT/disease 
assessment4
X
X
X
X
X
X
X
X4
X4
X4
X4
X4
X4
X4
Bone marrow assessment5
X
X
X
X
X
X
X
Survival status
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Local laboratory 
assessments
Blood draw for CBC 
with differential (local 
laboratory; for 
clinical/safety 
evaluation)6
X
X
X
X
X
X
X
Central laboratory 
assessments
Blood draw for CBC 
with differential (central 
laboratory)6
X
X
X
X
X
X
X
X
X
Blood draw for PBMCs 
for lymphocyte subsets 
and anti-CD19 CAR 
T cells7
X
X
X
X
X
X
X
X
X


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Procedure 
LTFU Period12
(Each visit calculated from Day 0)
Visit Frequency
Month 
6 
(± 2w)
Month 
9 
(± 2w)
Month 
12 
(± 2w)
Month 
15 
(± 2w)
Month 
18 
(± 2w)
Month 
21 
(± 2w)
Month 
24 
(± 1m)12
Month 
30 
(± 1m)
Month 
36 
(± 1m)
Month 
42 
(± 1m)
Month 
48 
(± 1m)
Month 
54 
(± 1m)
Month 
60 
(± 1m)
Month 72 
(± 3m) and 
Annually 
Thereafter 
Up to 
15 Years
Blood draw for PBMCs 
for RCR13
X
X
X13
X13
X13
X13
X13
Blood draw (plasma) for 
MRD analysis
X
X
X
X
Fresh tumor sample to 
central lab8
X
Targeted AE/SAEs9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Targeted concomitant 
therapies10
X
X
X
X
X
X
X
X
X
X
X
X
X
Subsequent therapy for 
MCL11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: AE, adverse event; CAR, chimeric antigen receptor; CBC, complete blood count; CR, complete response; EORTC-QLQ-C30, European Organisation for Research 
and Treatment of Cancer Quality of Life Questionnaire; EQ-5D, European Quality of Life-5 Dimensions; ICE, immune effector cell-associated encephalopathy; LTFU, long-term 
follow-up; m, month; MCL, mantle cell lymphoma; MRD, minimal residual disease; PBMC, peripheral blood mononuclear cell; PET-CT, positron emission 
tomography-computed tomography; PRO, patient-reported outcome; RCR, replication-competent retrovirus; SAE, serious adverse event; w, week.
1
PROs: Both PROs will be completed by the subject at the time points specified prior to any other assessments/procedures being performed, excluding blood draws and 
imaging.
2
Neurological assessment: If the ICE assessments performed at Week 4 and Month 3 had not returned to baseline (± 1 point), then continue to perform the assessment at 
Month 6 and every 3 months until the results have returned to baseline (± 1 point) or until Month 24.
3
Physical examinations will continue through the first 24 months.
4
PET-CT scans/disease assessments will continue through Month 24 or until disease progression, whichever comes first. If subject’s disease has not progressed by Month 24, 
disease assessments will continue to be performed per standard of care. 
5
Bone marrow assessment: As applicable, bone marrow aspirate or biopsy will be performed to confirm CR (ie, for subjects presenting with bone marrow involvement prior to 
therapy, for subjects without a bone marrow aspirate or biopsy at baseline, or if new abnormalities in the peripheral blood counts or blood smear cause clinical suspicion of 
bone marrow involvement with lymphoma after treatment). After CR is confirmed by bone marrow aspirate or biopsy, additional bone marrow aspirates or biopsies are only 
required in case of clinical suspicion of disease progression in the bone marrow only.


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6
Blood draw for CBC with differential:

Local laboratory: Blood will be collected at the time points specified through Month 24 or until disease progression, whichever occurs first, and sent to the local 
laboratory for clinical/safety evaluation.

Central laboratory: Subjects will continue to provide samples for central laboratory assessment of CBC with differential for pharmacokinetic assessments at the time 
points specified through Month 48 (these samples are distinct from samples collected and sent to the local laboratory for assessment of CBC with differential for 
clinical/safety evaluation).
7
PBMCs for lymphocyte subsets and anti-CD19 CAR T cells: Samples will continue to be collected at the time points specified through Month 48 even if PBMCs for RCR testing 
are no longer required to be collected.
8
Fresh (newly acquired) tumor sample for subjects who sign the optional portion of consent; refer to Section 7.11.1.
9
Targeted AE and SAE reporting will continue for 15 years or until disease progression or initiation of subsequent anticancer therapy (whichever occurs first). Any 
new/secondary malignancy, with the exception of a relapse of the primary malignancy, occurring after the administration of KTE-X19 should be reported as an SAE for up to 
15 years regardless of disease progression. Refer to Section 9.
10
Targeted concomitant therapies documentation will continue for 5 years or until disease progression or subsequent therapy (whichever occurs first).
11
Subsequent therapy administered after KTE-X19 infusion for a subject’s disease, such as nonstudy-specified chemotherapy, immunotherapy, targeted agents, as well as stem 
cell transplant and radiation therapy, must be collected until subject completes the LTFU period, is considered lost to follow-up, withdraws consent, or dies. Subjects may be 
contacted by telephone to collect information about subsequent therapy for MCL and to assess survival status.
12
After completion of at least 24 months of assessments in the KTE-C19-102 study, subjects who received an infusion of KTE-X19 will be provided an opportunity to transition 
to the LTFU study (KT-US-982-5968) after providing signed informed consent, to complete the remainder of the 15-year LTFU period.
13
PBMCs for RCR: In the follow-up period, samples will be collected at Months 6 and 12. Thereafter, samples will only be collected if an RCR event is clinically suspected 
and/or a subject’s PBMC sample tested positive for RCR at any time point within the first year. If the latter, samples will continue to be collected and tested annually for up to 
15 years or as clinically indicated. If a subject dies or develops a new/secondary malignancy during the study or follow-up, every effort should be made to collect blood and a 
biopsy sample of the neoplastic tissue or the pertinent autopsy tissue to assay for RCR.


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8.
SUBJECT WITHDRAWAL
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution.
Subjects can decline to continue to receive study required treatment and/or other 
protocol-required procedures at any time during the study but continue to participate in certain 
follow-up elements of the study. This is referred to as partial withdrawal of consent.
If partial withdrawal of consent occurs, the investigator must discuss with the subject the 
appropriate process for discontinuation from study treatment or other study-specific procedures 
and must discuss options for continued participation, completion of procedures, and the 
associated data collection as outlined in the SOA, including the following:

Survival status, including the cause of death

Safety reporting, including new malignancies; SAEs related to the anti-CD19 CAR T-cell 
product including, but not limited to, neurologic events, infections, blood, or immune 
disorders; and pregnancies

Targeted concomitant therapies (until 5 years after the antiCD19 CAR T-cell infusion, PD, or 
subsequent therapy, whichever occurs first)

Subsequent therapies

Central laboratory samples (per the SOA)
The level of follow-up and method of communication should also be discussed between the 
research staff and the subject and documented in the source documents.
Withdrawal of full consent for a study means that the subject does not wish to receive further 
protocol-required therapy or undergo study-specific procedures, and the subject does not wish to 
continue further study follow-up. The investigator is to discuss with the subject appropriate 
procedures for withdrawal from the study. If a subject withdraws full consent, the subject data 
collected up to withdrawal of consent will be retained and included in the analysis of the study 
and, where permitted by local regulations, publicly available data (eg, death records) can be 
included after withdrawal of consent.
As part of the study, sites may be asked to conduct searches of public records, such as those 
establishing survival status (eg, for subjects lost to follow-up), if available, to obtain survival 
data for any subject for whom the survival status is not known, per the applicable local laws.  
Sites may be also asked to retrieve autopsy reports to confirm status of disease at the time of 
death, if possible, per the local laws. 
The investigator and/or sponsor can also decide to withdraw a subject from the IP and/or other 
protocol-required therapies, protocol procedures, or the study as a whole at any time prior to 
study completion.


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8.1.
Reasons for Removal from Treatment
Reasons for removal from protocol-required IPs or procedures include any of the following:

AE

Subject request

Product not available

Lost to follow-up

Death

Decision by sponsor
8.2.
Reasons for Removal from Study
Reasons for removal of a subject from the study are as follows:

Subject withdrawal of consent from further follow-up

Investigator decision

Lost to follow-up 

Death

Termination of the study by the sponsor

Other (eg, noncompliance, refusal to consent to the LTFU study KT-US-982-5968)


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9.
SAFETY REPORTING
9.1.
AEs
An AE is defined as any untoward medical occurrence in a clinical trial subject.  The event does 
not necessarily have a relationship with study treatment.  The investigator is responsible for 
ensuring that any AEs observed by the investigator or reported by the subject are recorded in the 
subject’s medical record. 
The definition of AEs includes worsening of a pre-existing medical condition.  Worsening 
indicates that the pre-existing medical condition has increased in severity, frequency, and/or 
duration or has an association with a worse outcome.  A pre-existing condition that has not 
worsened during the study or involves an intervention, such as elective cosmetic surgery or a 
medical procedure, while on study is not considered an AE.
Interventions for pretreatment conditions (such as elective cosmetic surgery) or medical 
procedures that were planned before study participation are not considered AEs.  Hospitalization 
for study treatment infusions or precautionary measures per institutional policy are not 
considered AEs.
The term “disease progression” as assessed by measurement of malignant lesions on radiographs 
or other methods should not be reported as AEs.  Death due to disease progression in the absence 
of signs and symptoms should be reported as the primary tumor type (eg, MCL). 
For situations when an AE or SAE is due to the disease under investigation, report the signs and 
symptoms.  Worsening of signs and symptoms of the malignancy under study should also be 
reported as AEs in the appropriate section of the CRF. 
The investigator’s clinical judgment is used to determine whether a subject is to be removed 
from treatment due to an AE.  If a subject requests to withdraw from protocol-required therapies 
or the study due to an AE, the subject should undergo the procedures outlined in the Month 3 
visit of the SOA. 
9.2.
Reporting of AEs
The investigator is responsible for ensuring that all AEs observed by the investigator or reported 
by the subject that occur from enrollment (ie, commencement of leukapheresis) through 
3 months after treatment with anti-CD19 CAR T cell infusion are monitored and reported. 
After 3 months, only targeted AEs (ie, neurological events, hematological events, infections, 
GVHD or aggravation of GVHD, autoimmune disorders, and new/secondary malignancies) will 
be monitored and reported for 15 years after the initial anti-CD19 CAR T-cell infusion or until 
disease progression or initiation of subsequent anticancer therapy, whichever occurs first. Any 
new/secondary malignancy, with the exception of a relapse of the primary malignancy, occurring 
after the administration of KTE-X19 should be reported as an SAE for up to 15 years after the 
KTE-X19 infusion for all subjects, including those whose disease progresses.


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All AEs deemed related to the anti-CD19 CAR T-cell infusion should be recorded in the eCRF 
and reported regardless of the study period.
See Section 9.4 for reporting of non-serious CRS events Grade ≥ 3.
For subjects who are enrolled but do not receive anti-CD19 CAR T cells, the AE reporting 
period continues through 30 days after the last study-specific procedure (eg, leukapheresis, 
conditioning chemotherapy) or until initiation of a new anticancer therapy, whichever occurs 
first. 
The investigator must address the below AEs: 

AE diagnosis or syndrome (if not known, signs or symptoms)

Dates of onset and resolution

Severity

Assessment of relatedness to IP, conditioning chemotherapy, or study procedures

Action taken
AE grading scale used will be the NCI CTCAE version 4.03.  A copy of the grading scale can be 
downloaded from the Cancer Therapy Evaluation Program (CTEP) home page 
(http://ctep.cancer.gov).  In reviewing AEs, investigators must assess whether the AE is possibly 
related to 1) the IP (axicabtagene ciloleucel or KTE-X19), 2) conditioning chemotherapy, or 
3) any protocol-required study procedure.  The relationship is indicated by a yes or no response 
and entered into the CRF.  A yes response should indicate that there is evidence to suggest a 
causal relationship between the study treatment or procedure and the AE.  Additional relevant 
data with respect to describing the AE will be collected in the CRFs.
The investigator is responsible for reviewing laboratory test results and determining whether an 
abnormal value in an individual study subject represents a clinically significant change from the 
subject’s baseline values.  In general, abnormal laboratory findings without clinical significance 
(based on the investigator's judgment) are not to be recorded as AEs.  However, abnormal 
laboratory findings that result in new or worsening clinical sequelae, require therapy or 
adjustment in current therapy are considered AEs.  Where applicable, clinical sequelae (not the 
laboratory abnormality) are to be recorded as the AE.  
The investigator is expected to follow reported AEs until stabilization or resolution.  If a subject 
begins a new anti-cancer therapy, the AE reporting period for non-serious AE ends at the time 
the new treatment is started.
9.2.1.
Grading of CRS and Neurologic Events
For all subjects, the severity of CRS events will be reported using the Lee grading scale {Lee 
2014}, as outlined in Section 18.4 and the current IB. The severity of neurologic events will be 


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graded using CTCAE version 4.03. These grading systems will be used for toxicity management 
as described in the current IB.
For subjects in Cohort 3 only, in addition to the Lee criteria for CRS and CTCAE for neurologic 
events, CRS and ICANS will also be assessed by ASTCT grading {Lee 2019} (see Section 18.5 
and Section 18.6). ASTCT grading is collected only for the purposes of comparison and will not 
be used for toxicity management.
9.3.
Definition of SAEs
An SAE is defined as an AE that meets at least 1 of the following serious criteria:

Fatal

Life-threatening (places the subject at immediate risk of death)

Requires in-patient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Congenital anomaly/birth defect

Other medically important serious event
An AE would meet the criterion of “requires hospitalization” if the event necessitated an 
admission to a healthcare facility (eg, overnight stay). 
Events that require an escalation of care when the subject is already hospitalized should be 
recorded as an SAE.  Examples of such events include movement from routine care in the 
hospital to the intensive care unit (ICU) or if that event resulted in a prolongation of the existing 
planned hospitalization. 
If an investigator considers an event to be clinically important, but it does not meet any of the 
serious criteria, the event could be classified as an SAE with the criterion of “other medically 
important serious event.” 
The terms “severe” and “serious” are not synonymous.  Severity refers to the intensity of an AE 
according to NCI CTCAE criteria; the event itself may be of relatively minor medical 
significance and, therefore, may not meet the seriousness criteria.  Severity (ie, grade) and 
seriousness need to be independently assessed for each AE recorded on the eCRF.
9.4.
Reporting of SAEs and Non-serious CRS Events Grade ≥ 3
The investigator is responsible for reporting all SAEs observed by the investigator or reported by 
the subject that occur after signing of the consent through 3 months after the anti-CD19 CAR 
T-cell infusion or until initiation of subsequent anticancer therapy, whichever occurs first.
After 3 months, only targeted SAEs (ie, neurological events, hematological events, infections, 
GVHD or aggravation of GVHD, autoimmune disorders, and new/secondary malignancies) 


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observed by the investigator or reported by the subject will be reported for 15 years after the 
initial anti-CD19 CAR T-cell infusion or until disease progression or initiation of subsequent 
anticancer therapy, whichever occurs first. Any new/secondary malignancy, with the exception 
of a relapse of the primary malignancy, occurring after the administration of KTE-X19 should be 
reported as an SAE for up to 15 years after the KTE-X19 infusion for all subjects, including 
those whose disease progresses. 
For subjects who screen fail or are enrolled but do not receive anti-CD19 CAR T cells, the 
reporting period for SAEs continues through 30 days after the last study-specific procedure (eg, 
screen procedure, leukapheresis, conditioning chemotherapy) or until initiation of a new 
anticancer therapy, whichever occurs first. 
Serious events that the investigator assesses as related to axicabtagene ciloleucel or KTE-X19 
should be reported regardless of the time period. 
All SAEs and non-serious CRS events ≥ Grade 3 {Lee 2014} must be submitted to Kite Pharma 
via email to 
 within 24 hours following the investigator’s knowledge of 
the event using a SAE Report Form for subjects in Cohorts 1 and 2. For subjects in Cohort 3, 
SAEs should be submitted via Safety Gateway within RAVE EDC. 
Following completion of KTE-C19-102, any relevant information on ongoing SAEs must be 
submitted to Kite Pharma within 24 hours of the investigator’s knowledge of the event using the 
paper SAE Report Form and sent via email to the SAE reporting mailbox: 
, in the context of study KT-US-982-5968.
Subsequently, all SAEs will be reported in accordance with EU guidelines, or, if applicable, as 
per local reporting guidelines. 
Progression of the malignancy during the study should not be reported as an SAE.  SAEs 
associated with disease progression may be reported as an SAE.  If the malignancy has a fatal 
outcome within 3 months of the last day of the conditioning therapy or anti-CD19 CAR T cell-
infusion, then the event leading to death must be recorded as an SAE with CTCAE Grade 5.
Death must be reported if it occurs during the SAE reporting period, irrespective of any 
intervening treatment.
Any death occurring after the first dose of chemotherapy, for the purpose of pre-conditioning, 
and within 3 months of the anti-CD19 CAR T cell infusion, regardless of attribution to treatment, 
requires expedited reporting within 24 hours.  Any death occurring greater than 3 months after 
the anti-CD19 CAR T cell infusion requires expedited reporting within 24 hours only if it is 
considered related to treatment.
9.5.
Reporting Deaths
Deaths that occur during the protocol-specified AE reporting period that are attributed by the 
investigator solely to progression of underlying lymphoma should be recorded as SAEs with the 
preferred term “B-cell lymphoma” and must be reported immediately to the sponsor.  Death is an 
PPD
PPD


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outcome and not a distinct event.  The event or condition that caused or contributed to the fatal 
outcome should be recorded on the AE form.  The term “unexplained death” should be captured 
if the cause of death is not known.  However, every effort should be made to capture the 
established cause of death, which may become available later (eg, after autopsy).  Deaths during 
the post-study survival follow-up that are due to underlying cancer should be recorded only on 
the Survival Status CRF.
9.6.
Diagnosis Versus Signs and Symptoms
For AEs, a diagnosis (if known) rather than individual signs and symptoms should be recorded 
on the AE form.  The exception is for CRS where both the diagnosis and signs and symptoms 
will be captured on the CRF AE form.  For signs and symptoms of the underlying cancer, the 
signs and symptoms should be captured.  However, on the AE form, the investigator should state 
that these signs and symptoms are due to the underlying disease.
9.7.
Pregnancy and Lactation
There is no relevant clinical experience with KTE-X19 in pregnant or lactating females, and 
animal reproductive studies have not been performed. This experimental therapy should not be 
administered to pregnant females or females who are breastfeeding. Females of childbearing 
potential must have a negative pregnancy test prior to enrollment because of the potentially 
dangerous effects of the preparative chemotherapy on the fetus. Females of childbearing 
potential should be monitored according to local and country-specific regulations. Refer to 
Section 18.7 for the definition of childbearing potential.
Female subjects and female partners of male subjects are recommended to use highly effective 
contraception (method must achieve an annual failure rate of < 1%) for at least 6 months after 
conditioning chemotherapy dosing or KTE-X19 administration, whichever is longer. Male 
subjects are recommended to not father a child for at least 6 months after completion of 
conditioning chemotherapy dosing or KTE-X19 administration, whichever is longer. Refer to 
Section 18.7 for a complete list of highly effective contraception methods.
Pregnancy testing will occur at the time points indicated in the SOAs.
If a pregnancy occurs in either a female subject enrolled into the study or a female partner of a 
male subject within 6 months of completing conditioning chemotherapy or the administration of 
KTE-X19, whichever is longer, the pregnancy must be reported to the key sponsor contact.  
Information regarding the pregnancy and/or the outcome may be requested by the key sponsor. 
In addition to reporting any pregnancies occurring during the study, investigators should monitor 
for pregnancies that occur after the last dose of anti-CD19 CAR T cell infusion through 6 months 
for female subjects and for 6 months for the female partner of the male subjects. Any 
pregnancies that occur > 6 months after CAR T-cell infusion should also be reported if the 
investigator incidentally becomes aware of such a pregnancy.
The pregnancy should be reported to the key sponsor contact within 24 hours of the 
investigator’s knowledge of the pregnancy event. 


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If a lactation case occurs while the female subject is taking protocol-required therapies, report 
the lactation case to the key sponsor contact.
In addition to reporting a lactation case during the study, investigators should monitor for 
lactation cases that occur after the last dose of protocol-required therapies through 6 months.
Any lactation case should be reported to the key sponsor contact within 24 hours of the 
investigator’s knowledge of the event.
9.8.
Hospitalization and Prolonged Hospitalization
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as an SAE as described in Section 9.4.  
The following hospitalization scenarios are not considered to be SAEs:

Hospitalization for palliative care or hospice care

Planned hospitalization required by the protocol (eg, for monitoring of the subject or to 
perform an efficacy measurement for the study)

Planned hospitalization for a pre-existing condition

Hospitalization due to progression of the underlying cancer
9.9.
Abnormal Vital Signs Values
Not all vital sign abnormalities qualify as an AE.  A vital sign result must be reported as an AE if 
it is a change from baseline and meets any of the following criteria:

Accompanied by clinical symptoms

Results in a medical intervention or a change in concomitant therapy

Clinically significant in the investigator’s judgment
It is the investigator’s responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality should be 
classified as an AE.  However, if a clinically significant vital sign abnormality is a sign of a 
disease or syndrome (eg, high blood pressure), only the diagnosis (ie, hypertension) should be 
recorded on the CRF.
9.10.
DSMB
9.10.1.
Cohort 1 and Cohort 2
An independent DSMB will review safety and/or efficacy data from Cohort 1 and Cohort 2 at 
4 times during this study.  The DSMB will first meet to review safety data when 10 subjects in 
Cohort 1 have been enrolled and treated with anti-CD19 CAR T cells and followed for 30 days.  
The DSMB will meet for the second time to review both safety and efficacy data after 


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20 subjects in Cohort 1 have been treated with anti-CD19 CAR T cells and have had the 
opportunity to complete the 3-month disease assessment.  The DSMB will meet for the third time 
to review both safety and efficacy data after 10 subjects in Cohort 2 have been treated with 
KTE-X19 and have had the opportunity to be followed for 30 days.  The DSMB will meet for the 
fourth time after 44 subjects in Cohort 1 have been treated with anti‑CD19 CAR T cells and 
have had opportunity to be followed for 30 days after the IP infusion. The DSMB will be 
chartered to make trial conduct recommendations for Cohort 1 and Cohort 2 based on an analysis 
of risk vs benefit.  The DSMB may meet more often as needed. 
As part of its oversight of the study, the DSMB also will assess criteria to pause enrollment after 
10, 20, 30, and 50 subjects in Cohort 1 have been treated with axicabtagene ciloleucel or 
KTE-X19 and have had the opportunity to be followed for 30 days, using the criteria described 
in Section 9.12.
9.10.2.
All Cohorts
At the time of expedited reporting of suspected unexpected serious adverse reactions (SUSARs) 
to health authorities, Kite (or designee) will concurrently submit these reports to the DSMB 
chair.  The DSMB chair will also review SAE narrative reports quarterly.  Finally, the DSMB or 
Kite may request additional analyses of safety data if a safety concern arises during the course of 
the trial.
9.11.
Scientific Steering Committee (Cohort 3)
A scientific steering committee, comprising the study sponsor and at least 3 study investigators, 
will be specifically chartered to review the safety data from Cohort 3 and make 
recommendations on further study conduct. The scientific steering committee will meet after 
15 subjects in Cohort 3 have been enrolled and treated with KTE-X19 and have had the 
opportunity to be followed for 30 days, and again after 50 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed for 3 months. 
The scientific steering committee may meet more often as needed.
As part of its oversight of the study, the scientific steering committee will also assess criteria to 
pause enrollment in Cohort 3 after 15 subjects in Cohort 3 have been enrolled and treated with 
KTE-X19 and have had the opportunity to be followed for 30 days, and again after 50 subjects in 
Cohort 3 have been enrolled and treated with KTE-X19 and have had the opportunity to be 
followed for 3 months, using the criteria described in Section 9.12.
The scientific steering committee may request additional analyses of safety data if a safety 
concern arises during the course of the trial.
9.12.
Criteria to Pause Enrollment
Enrollment will be paused if any of the following criteria are met as determined by the DSMB 
(Cohort 1 and Cohort 2; see Section 9.10.1) or scientific steering committee (Cohort 3; see 
Section 9.11) at the prespecified time points:


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
Subject incidence of Grade 5 axicabtagene ciloleucel or KTE-X19 related AEs within 
30 days is > 10%
or

Subject incidence of the following Grade 4 axicabtagene ciloleucel or KTE-X19-related AEs 
lasting more than 7 days is > 33%:
Neurologic toxicity
CRS (per Lee 2014 criteria)
Other non-hematological Grade  4 SAE
Infection (treatment-related)


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10.
STATISTICAL CONSIDERATIONS
10.1.
Hypothesis
This study uses an open-label, 3-cohort design.  
An alternative hypothesis will be tested among Cohort 1 KTE-X19 subjects with a target 50% 
ORR per independent review against a null hypothesis that the ORR is 25% or less.  The 
hypothesis is that the ORR to KTE-X19 in Cohort 1 KTE-X19 subjects is significantly greater 
than 25%. 
Additionally, an alternative hypothesis will be tested among Cohort 3 subjects with a target 75% 
ORR per independent review against a null hypothesis that the ORR is 57% or less. The 
hypothesis is that the ORR to KTE-X19 per independent review is significantly greater than 57% 
in Cohort 3 subjects. 
No hypothesis will be tested in Cohort 1 axicabtagene ciloleucel subjects and Cohort 2 subjects. 
10.2.
Study Endpoints
10.2.1.
Primary

ORR: Defined as the incidence of a CR or a PR per the Lugano Classification {Cheson 
2014}, as determined by the IRRC.  All subjects who do not meet the criteria for an objective 
response by the analysis cutoff date will be considered non-responders, including the subjects 
without any evaluable assessment and those without any assessment.
10.2.2.
Secondary

DOR: For subjects who experience an objective response, DOR is defined as the time from 
their first objective response to disease progression or death.  Subjects not meeting the 
criteria for progression or death by the analysis data cutoff date will be censored at their last 
evaluable disease assessment date and their response will be noted as ongoing  

Best objective response: the incidence of CR, PR, SD, PD, or unevaluable as best response to 
treatment

ORR (as determined by investigators): For subjects enrolled in Cohort 1, ORR, as 
determined by study investigators, is defined as the incidence of either a CR or PR per the 
revised IWG Response Criteria for Malignant Lymphoma {Cheson 2007}.  For subjects 
enrolled in Cohort 2 and Cohort 3, ORR, as determined by investigators, is defined as the 
incidence of either a CR or PR per the Lugano Classification {Cheson 2014}.  All subjects 
who do not meet the criteria for an objective response by the analysis data cutoff date will be 
considered non-responders, including the subjects without any evaluable assessment and 
those without any assessment.


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• 
PFS: defined as the time from the anti -CD 19 CAR T-cell infusion date to the date of disease 
progression or death from any cause. Subjects not meeting the criteria for progression by the 
analysis data cutoff date will be censored at their last evaluable disease assessment date. 
• 
OS: defined as the time from anti-CD19 CART cell infusion to the date of death from any 
cause. Subjects who have not died by the analysis data cutoff date will be censored at the 
last date known alive or the data cutoff date for analysis, whichever is earlier. 
• 
Incidence of AEs and clinically significant changes in laborato1y values 
• 
Incidence of anti-CD19 CAR antibodies, levels of antiCD19 CART cells in blood, and levels 
of cytokines in sernm 
• 
Changes over time in the EQ-5D scale score and EQ-5D VAS score 
• 
Changes in the EORTC-QLQ-C30 score from baseline over time (Coho1i 3 only) 
10.2.3. 
Exploratory Endpoints 
I 
10.3. 
Sample Size Considerations 
This study uses an open-label, 3-cohoii design to test for an improvement in ORR. Up to 
approximately 220 subjects with r/r MCL will be emolled and treated with anti-CD19 CAR 
T cells, including 10 axicabtagene ciloleucel subjects and up to approximately 80 KTE-X19 
subjects in Coho1i 1, up to 40 KTE-X19 subjects in Cohort 2, and up to approximately 
90 KTE-X19 subjects in Coho1i 3. 
The prima1y analysis in Coho1i 1 will be conducted after 60 Coho1i 1 KTE-X19 subjects have 
been emolled and treated and have had the opportunity to be evaluated for response 6 months 
after the Week 4 disease assessment. For the test of efficacy in Coho1i 1, 60 KTE-X19 subjects 
in Coho1i 1 will provide at least 96% power to distinguish between an active therapy with a 50% 
trne response rate from a therapy with a response rate of25% or less (undesirable response rate, 
for pmposes of futility assessment) with a I-sided alpha level of 0.025. 
The primaiy analysis in Cohort 3 will be conducted after 86 subjects in Cohort 3 have been 
emolled and treated with KTE-X19 and have had the oppo1iunity to be assessed for response 
6 months after the first objective response or 9 months after the KTE-X19 infusion, whichever is 
earlier. For the test of efficacy in Coho1i 3, a sample size of 86 subjects will provide at least 90% 
power to distinguish between an active therapy with a 75% hue response rate and a therapy with 
a response rate of 57% or less with a I-sided alpha level of 0.025. 
No hypothesis will be tested in Coho1i 1 axicabtagene ciloleucel subjects or Coho1i 2 subjects. 
Explorato1y analyses will be conducted on the data collected from these subjects. 
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In Cohort 1, 4 interim analyses will be performed:  

Cohort 1 interim analysis 1 will be conducted after 10 subjects in Cohort 1 have been 
enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be 
followed for 30 days.  This interim analysis will be for safety only.

Cohort 1 interim analysis 2 will be conducted after 20 subjects in Cohort 1 have been 
enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be 
evaluated for response 3 months after treatment with anti‑CD19 CAR T cells.  In this interim 
analysis, the DSMB will review data for both safety and efficacy (futility only).

Cohort 1 interim analysis 3 will occur after 38 subjects in Cohort 1 have been treated with 
anti‑CD19 CAR T cells and have had the opportunity to be assessed for response 6 months 
after the treatment with anti‑CD19 CAR T cells.  This interim analysis will be performed for 
a Kite internal review of the accumulating data of safety and efficacy.

Cohort 1 interim analysis 4 will occur after 44 subjects in Cohort 1 have been treated with 
anti‑CD19 CAR T cells and have had the opportunity to be followed for at least 30 days.  In 
this interim analysis, the DSMB will review data for safety only, with focus on the 6 KTE-X19 
subjects treated most recently in this cohort.
In Cohort 2, one interim analysis will be performed:

Cohort 2 interim analysis will be conducted after 10 subjects in Cohort 2 have been enrolled 
and treated with KTE-X19 and have had the opportunity to be followed for 30 days after 
treatment with KTE-X19.  This interim analysis will be for safety and efficacy.
In Cohort 3, two interim analyses will be performed for safety only:

Cohort 3 interim analysis 1 will be conducted after 15 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed for 30 days 
after the KTE-X19 infusion. 

Cohort 3 interim analysis 2 will be conducted after 50 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed for 
3 months after the KTE-X19 infusion.
Accrual to the study will continue during all interim analyses.
Two primary analyses will be performed:

One primary analysis will be performed with both Cohort 1 and Cohort 2 after 60 KTE-X19 
subjects in Cohort 1 have been enrolled and treated and have had the opportunity to be 
assessed for response 6 months after the Week 4 disease assessment.
At this primary analysis, the inferential testing will be performed with data from the Cohort 1 
KTE-X19 subjects only, using a 1-sided alpha level of 0.025.  This procedure preserves the 
designated overall alpha level (1-sided) of 0.025 and has at least 96% power when 


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60 KTE-X19 subjects are included.  EAST version 6.4 were used for power calculation and 
evaluation of the operating characteristics of this design.
For Cohort 1, a rho (parameter = 0.30) beta spending function will be used to allocate the 
beta level between the futility analysis and the primary efficacy analysis.  

The primary analysis in Cohort 3 will be conducted after 86 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be assessed for response 
6 months after the first objective response or 9 months after the KTE-X19 infusion, 
whichever is earlier. In this analysis, inferential testing on efficacy in Cohort 3 will be 
performed using a 1-sided alpha level of 0.025. This procedure preserves the designated 
overall alpha level (1-sided) of 0.025 and has at least 90% power when 86 subjects are 
included. EAST version 6.5 was used for power calculation and evaluation of the operating 
characteristics of this design.
10.4.
Statistical Assumptions
As described in Section 3, an open-label, 3-cohort design is used. In Cohort 1, a target response 
rate of 50% and a historical control rate of 25% are assumed for statistical inference. In Cohort 3, 
a target response rate of 75% and a historical control rate of 57% are assumed for statistical 
inference (see Section 2.2.1.1 for additional information about the historical control rate). The 
responses from subjects in the study population are assumed to be independent and follow 
binomial distribution, and, thus, the exact binomial test will be used to test the statistical 
hypothesis. 
10.5.
Analysis Subsets 

mITT set: will consist of all subjects enrolled and treated with anti‑CD19 CAR T cells at any 
dose.  This analysis set will be used for analyses of the efficacy endpoints (ORR, best 
objective response, DOR, PFS, OS) for the study. This analysis set will also be used for the 
hypothesis testing of the primary endpoint ORR in Cohort 3.  

Inferential analysis set: will consist of the first 60 treated KTE-X19 subjects in Cohort 1. 
This analysis set will be used for the hypothesis testing of the primary endpoint ORR at the 
time of the primary analysis in Cohort 1, as well as the analyses on the key secondary 
endpoints (best objective response [BOR], DOR, PFS, and OS).

Safety analysis set: defined as all subjects treated with any dose of anti‑CD19 CAR T cells.  
This analysis set will be used for all analyses of safety.

Full analysis set (FAS): will consist of all enrolled subjects and will be used for the summary 
of subject disposition, sensitivity analyses of ORR and key secondary endpoints, and subject 
listings of deaths.
10.6.
Access to Individual Subject Treatment Assignments
This is an open-label, 3-cohort study, and subjects and investigators will be aware of treatment 
received.  Data handling procedures for the study will be devised to reduce potential sources of 


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bias and maintain the validity and credibility of the study.  These procedures will be outlined in 
the study Statistical Analysis Plan, DSMB charter, scientific steering committee charter, and 
Trial Integrity Document.
10.7.
Interim Analysis
10.7.1.
Interim Analysis and Early Stopping Rules
In Cohort 1 and Cohort 2, an independent DSMB will be formed to review accumulating safety 
data after 10 subjects in Cohort 1 have been enrolled and treated with anti‑CD19 CAR T cells 
and have had the opportunity to be followed for 30 days for safety.  The DSMB will review 
accumulating safety and efficacy data after 20 subjects in Cohort 1 have been treated with anti‑
CD19 CAR T cells and have had the opportunity to complete the 3-month disease assessment 
after the treatment with anti‑CD19 CAR T cells.  The DSMB will also review safety and 
efficacy after 10 subjects in Cohort 2 have been treated with KTE-X19 and have had opportunity 
to be followed for 30 days after the KTE-X19 infusion. The DSMB will review safety again after 
44 subjects in Cohort 1 have been enrolled and treated with anti‑CD19 CAR T cells and have 
had the opportunity to be followed for 30 days after the treatment with anti‑CD19 CAR T cells, 
with focus on the safety data from the 6 KTE-X19 subjects treated most recently within this 
cohort.
In Cohort 3, the scientific steering committee will review safety data after 15 subjects in 
Cohort 3 have been enrolled and treated with KTE-X19 and have had the opportunity to be 
followed for 30 days after the KTE-X19 infusion. The scientific steering committee will also 
review safety data after 50 subjects in Cohort 3 have been enrolled and treated with KTE-X19 
and have had the opportunity to be followed for 3 months after the KTE-X19 infusion.
The DSMB and scientific steering committee will also monitor safety criteria to pause 
enrollment in the respective cohorts (see Section 9.12).
10.7.2.
Safety Interim Analysis  
In Cohort 1, the DSMB will review the safety data twice, after 10 and 44 subjects in Cohort 1 
have been enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be 
followed for 30 days for safety, respectively. 
In Cohort 3, the scientific steering committee will review the safety data twice, once after 
15 subjects in Cohort 3 have been enrolled and treated with KTE-X19 and have had the 
opportunity to be followed for 30 days after the KTE-X19 infusion, and again after 50 subjects in 
Cohort 3 have been enrolled and treated with KTE-X19 and have had the opportunity to be 
followed for 3 months after the KTE-X19 infusion.
The DSMB will also review SAE information and SUSARs on a regular basis throughout subject 
treatment in the study.  The DSMB may request additional safety data or modifying the study 
conduct.  The sponsor may request additional reviews by the DSMB if safety concerns are 


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identified.  Data submitted to the DSMB may be monitored or unmonitored to facilitate and 
ensure timely DSMB review.  
10.7.3.
Efficacy Interim Analysis
In Cohort 1, two efficacy interim analyses will be performed.  
Interim analysis 2 (Efficacy analysis 1) will be conducted after 20 subjects have been treated 
with anti‑CD19 CAR T cells and have had the opportunity to be followed for 3 months after the 
treatment with anti‑CD19 CAR T cells.  This interim analysis will be for futility only.  If more 
than 5 responses are observed in the first 20 subjects, accrual in Cohort 1 will continue. 
Interim analysis 3 (Efficacy analysis 2) will be conducted after 38 subjects in Cohort 1 have been 
treated with anti‑CD19 CAR T cells and have had the opportunity to be assessed for response 
6 months after the treatment with anti‑CD19 CAR T cells. This interim analysis will be 
performed for a Kite internal review of the accumulating data of safety and efficacy.
A rho (parameter = 0.30) beta spending function will be used to allocate the beta level between 
this futility analysis and the primary efficacy analysis in Cohort 1.    
In Cohort 2, one interim analysis will be conducted after 10 KTE-X19 subjects have been 
enrolled and have had the opportunity to be followed for 30 days after treatment with KTE-X19. 
This interim analysis will be for safety and efficacy.  
No interim analyses for efficacy will be performed in Cohort 3.
10.7.4.
Other Interim Analysis
The sponsor reserves the right to conduct additional analyses of safety and efficacy during the 
time between the planned interim analyses and primary analyses for regulatory interaction 
purposes. If conducted, no formal hypothesis testing will be performed in such analyses.
10.8.
Planned Methods of Analysis
10.8.1.
Primary and Additional Analyses
10.8.1.1.
Cohort 1 and Cohort 2
The primary analysis will be performed after 60 KTE-X19 subjects in Cohort 1 have been treated 
and have had the opportunity to be evaluated for response 6 months after the Week 4 disease 
assessment. In this primary analysis, inferential testing of efficacy will be performed with data 
from Cohort 1 KTE-X19 subjects only, and the analysis with the data from Cohort 1 
axicabtagene ciloleucel subjects and Cohort 2 will be descriptive. 
Additional analyses may occur after the primary analysis has been completed. These additional 
analyses will be descriptive and will occur after inferential testing in Cohort 1 has been 
performed. A follow-up analysis of subjects treated with KTE-X19 will be performed after all 
subjects in the mITT set of Cohort 1 have had the opportunity to be assessed for response 


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18 months after the first objective response. This additional analysis will be descriptive. The 
final analysis of Cohort 1 and Cohort 2 will occur when all subjects in both cohorts have 
completed the study.  
10.8.1.2.
Cohort 3
The primary analysis, including inferential testing on the primary efficacy endpoint (ORR), will 
be conducted after 86 subjects in Cohort 3 have been enrolled and treated with KTE-X19 and 
have had the opportunity to be assessed for response 6 months after the first objective response 
or 9 months after the KTE-X19 infusion, whichever is earlier.
A follow-up analysis will be performed after 86 subjects in Cohort 3 have had the opportunity to 
be assessed for response 18 months after the first objective response to further evaluate the 
risk-benefit profile of KTE-X19, including the durability of response. This analysis will be 
descriptive. 
Additional descriptive analyses may occur after the primary analysis and follow-up analyses 
described above have been completed. The final analysis of Cohort 3 will occur when all 
subjects in Cohort 3 have completed the study.
10.8.2.
ORR
The incidence of objective response and exact 2-sided 95% confidence intervals will be 
generated for Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, Cohort 2 
subjects, and Cohort 3 subjects. An exact binomial test will be used to compare the observed 
ORRs per IRRC review in Cohort 1 KTE-X19 subjects and Cohort 3 subjects to response rates of 
25% and 57%, respectively.
The primary endpoint of ORR will be based on IRRC review of disease assessments. Analyses of 
ORR based on investigator review of disease assessments will also be performed.
10.8.3.
Best Objective Response
The incidence of subjects with CR, PR, SD, PD, and unevaluable as best response to treatment 
and exact 2-sided 95% confidence intervals about the incidence will be generated for Cohort 1 
KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, Cohort 2 subjects, and Cohort 3 
subjects.
10.8.4.
DOR
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for DOR for 
Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, Cohort 2 subjects, and 
Cohort 3 subjects. DOR will be derived using disease assessments obtained on study prior to 
initiation of new anti-cancer therapy (including SCT).  The DOR for subjects who undergo SCT 
while in remission will be censored at the last evaluable assessment date prior to SCT; a 
sensitivity analysis will be conducted in which disease assessments obtained after SCT are 
included in the derivation of DOR. 


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10.8.5.
PFS
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for PFS time for 
Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, Cohort 2 subjects, and 
Cohort 3 subjects. Estimates of the proportion of subjects alive and progression-free at 3-month 
intervals will be provided.
10.8.6.
OS
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS for 
Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, Cohort 2 subjects, and 
Cohort 3 subjects. Estimates of the proportion of subjects alive at 3-month intervals will be 
provided.
10.8.7.
Safety
Subject incidence rates of AEs, including all, serious, fatal, CTCAE version 4.03 Grade 3 or 
higher, and treatment-emergent AEs (TEAEs) with onsets on or after the date of KTE-X19 or 
axicabtagene ciloleucel infusion, will be tabulated by preferred terms and system organ class.  
Changes in laboratory values and vital signs will be summarized with descriptive statistics.  The 
incidence of concomitant medications will be summarized.
Tables and/or narratives of deaths through the LTFU and treatment related SAEs will be 
provided.
10.8.8.
Long-term Data Analysis
All subjects will be followed for survival status for up to 15 years after receiving KTE-X19 or 
axicabtagene ciloleucel infusion. LTFU data analysis will be performed on subjects in this study 
and after transition to the KT-US-982-5968 LTFU study. No formal hypothesis testing will be 
performed based on data obtained after the primary analysis in each cohort. Descriptive estimates 
of key efficacy and safety analyses may be updated to assess the overall treatment profile.


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11.
REGULATORY OBLIGATIONS
11.1.
Independent Review Board/Independent Ethics Committee 
A copy of the protocol, ICF, and any additional subject or trial information, such as subject 
recruitment materials, must be submitted to each site’s respective IRB/IEC for approval.  After 
approval is obtained from the IRB/IEC, all documents must be provided to the key sponsor 
contact before subject recruitment can begin.
The investigator must also receive IRB/IEC approval for all protocol and ICF changes or 
amendments.  Investigators must ensure that ongoing/continuous IRB/IEC approval (ie, annual 
approval) is provided throughout the conduct of the study.  Copies of IRB/IEC approval are to be 
forwarded to the key sponsor contact for archiving.
During the course of the study, investigators are to submit site-specific and study SAEs 
(provided to the site by the key sponsor contact), along with any protocol deviations, to their 
IRB/IEC in accordance with their respective IRB/IEC policies. 
11.2.
Subject Confidentiality
Subject confidentiality must be maintained for all material submitted to the key sponsor contact.  
The following rules are to be applied.

Subjects will be identified by a unique ID number.

Date of birth or year of birth/age at time of enrollment will be reported according with local 
laws and regulations.
For reporting of SAEs, subjects will be identified by their respective subject ID number, initials, 
and date of birth or year of birth (as per their local reporting requirements for both initials and 
date of birth).
Per federal regulations and International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use/Good Clinical Practice (ICH/GCP) guidelines, investigators 
and institutions are required to permit authorization to the sponsor, Contract Research 
Organization (CRO), IRB/IEC, and regulatory agencies to subject’s original source documents 
for verification of study data.  The investigator is responsible for informing potential subjects 
that such individuals will have access to their medical records, which includes personal 
information.


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11.3.
Investigator Signatory Obligations
Each clinical study report will be signed by the coordinating investigator.  The coordinating 
investigator will be identified by Kite under the following criteria:

A recognized expert in the disease setting

Provided significant contributions to the design or analysis of study data

Participated in the study and enrolled a high number of eligible subjects
11.4.
Ethics
Study KTE-C19-102 will be conducted under a US IND application or equivalent and in 
accordance with recognized international scientific and ethical standards, including but not 
limited to the ICH guideline for GCP, and the original principles embodied in the Declaration of 
Helsinki. These standards are consistent with the requirements of the US Code of Federal 
Regulations Title 21, Part 312, and the European Community Directive 2001/20/EC, as well as 
other local legislation.


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12.
PROTOCOL AMENDMENTS AND TERMINATION
If the protocol is amended, the Investigator’s Agreement with the amendment and the IRB/IEC 
approval of the amendment must be obtained.  Documentation acknowledging approval from 
both parties is to be submitted to the key sponsor contact.
Both Kite and the investigator reserve the right to terminate the investigator’s participation in the 
study as per the terms of the agreement in the study contract.  The investigator is to provide 
written communication to the IRB/IEC of the trial completion or early termination and provide 
the CRO with a copy of the correspondence.
Kite reserves the unilateral right, at is sole discretion, to determine whether to manufacture CAR 
T cells and provide them to sites and subjects after the completion of the study and before 
treatment becomes commercially available.


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13.
STUDY DOCUMENTATION AND ARCHIVE
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated.  These individuals authorized to fulfil these responsibilities should be outlined and 
included in the Delegation of Authority Form.
Source documents are original documents, data, and records for which the study data are 
collected and verified.  Example of such source documents may include, but are not limited to, 
hospital records and patient charts; laboratory, pharmacy, radiology, and records; subject diaries; 
microfiches; correspondence; and death registries.  CRF entries may be considered as source data 
if the site of the original data collection is not available.  However, use of the CRFs as source 
documentation as a routine practice is not recommended.
The investigator and study staff are responsible for maintaining a comprehensive filing system of 
all subject records that are readily retrieved to be monitored and/or audited at any time by the 
key sponsor contact (or delegate), regulatory authorities, and IRB/IECs.  The filing system will 
include at minimum:

Subject content including ICFs and subject ID lists

Essential documents for the conduct of this clinical study

Proof of receipt, experimental treatment flow records, and experimental product-related 
correspondence.
Original source documents supporting entries into CRFs must be maintained at the site and 
readily available upon request.  No study documents should be discarded without prior written 
agreement between Kite and the investigator.  Should storage no longer be available to archive 
source documents or must be moved to an alternative location, the research staff should notify 
the key sponsor contact prior to shipping the documents.
The required source data should include sequential notes containing at least the following 
information for each subject:

Subject ID

Documentation that subject meets eligibility criteria (ie, medical history, physical 
examination, and confirmation of diagnosis [to support inclusion and exclusion criteria])

Documentation of the reason(s) a consented subject is not enrolled

Participation in study (including study number/name)

Study discussed and date of informed consent

Dates of all visits


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
Documentation that protocol-specific procedures were performed

Results of efficacy parameters, as required by the protocol

Start and end date (including dose regimen) of IP, including start and stop times of 
axicabtagene ciloleucel or KTE-X19 administration 

Record of all AEs and other safety parameters (start and end date, and including causality 
and severity), and documentation that adequate medical care has been provided for any AE

Concomitant medication (including start and end date, dose if relevant, and dose changes)

Date of study completion and reason for early discontinuation, if it occurs
Traceability records for the product, from procurement through manufacture to the 
administration of the product, should be kept by each relevant party (eg, the sponsor, the 
investigator/institution) for a minimum of 30 years after the expiry date of the product, or longer 
if required by the terms of the clinical trial authorization or by agreement with the sponsor. 
Before, during, and after completion or termination of the trial, each party should hold the 
necessary information available at all times to ensure bidirectional traceability, linking the 
subject information at the procurement site to the product and the subject information at the 
clinical trial site to the product, while ensuring the data protection legally required for the 
subject.
If the investigator cannot provide for this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Kite to store 
these records securely away from the site so that they can be returned sealed to the investigator 
in case of an inspection. When source documents are required for the continued care of the 
subject, appropriate copies should be made for storage away from the site.
If a subject transfers to another study site, the investigator must notify Kite in advance before 
assigning the subject’s study records to another party or moving them to another location.


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14.
STUDY MONITORING AND DATA COLLECTION
The key sponsor contact, monitors, auditors, or regulatory inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and verifying 
source documents and records assuring that subject confidentiality is respected.
The monitor is responsible for source document verification of CRF data at regular intervals 
during the study.  Protocol adherence, accuracy, and consistency of study conduct and data 
collection with respect to local regulations will be confirmed.  Monitors will have access to 
subject records as identified in Section 13.
By signing the Investigator’s Agreement, the investigator agrees to cooperate with the monitor to 
address and resolve issues identified during monitoring visits.
In accordance with ICH/GCP and the audit plan, a site may be chosen for a Kite Quality 
Assurance site audit. A Kite Quality Assurance site audit would include, but is not limited to, an 
inspection of the facility(ies), review of subject and study-related records, and compliance with 
protocol requirements as well as ICH/GCP and applicable regulatory policies. Investigators will 
provide Kite Quality Assurance auditors access to subject records.
Representatives of regulatory authorities may conduct inspections of the clinical study. If the 
investigator is notified of an inspection by a regulatory authority, the investigator agrees to notify 
the Kite medical monitor immediately. The investigator agrees to provide to representatives of a 
regulatory agency access to records, facilities, and personnel for the effective conduct of any 
inspection or audit.
All data will be collected in an electronic CRF system.  All entries must be completed in English, 
and concomitant medications should be identified by tradenames.  For further details 
surrounding the completion of CRFs, refer to the CRF completion guidelines.


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15.
PUBLICATION
Authorship of publications from data generated in study KTE-C19-102 will be determined based 
on the uniform requirements for manuscripts submitted to biomedical journals (as outlined in the 
International Committee of Medical Journal Editors December 2013) which states: 

Authorship should be based on:
Substantial contributions to the conception or design of the work, acquisition of data, 
analysis, or interpretation of data for the work; and
Drafting the article or revising it critically for important intellectual content; and
Final approval of the version to be published; and
Agreement to be accountable for all aspects of the work in ensuring that questions related 
to the accuracy or integrity of any part of the work re appropriately investigated or 
resolved
When a large, multicenter group has conducted the work, the group should identify the 
individuals who accept direct responsibility for the manuscript.  This individual should fully 
meet the criteria for authorship defined above.
Funding, collection of data, or general supervision of the research alone or in combination does 
not qualify an individual for authorship.
Any publication, in any form, that is derived from this study must be submitted to Kite for 
review and approval.  The study contract among the institution, principal investigator, and Kite 
or its delegate will outline the requirements for publication review.


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16.
COMPENSATION
Kite has insurance that provides compensation for study-related illness or injury pursuant to the 
information outlined in the injury section of the ICF.
Investigators and their study staff may be asked to provide services performed under this 
protocol (eg, attendance at investigator meetings). If required under the applicable statutory and 
regulatory requirements, Kite will capture and disclose to federal and state agencies any 
expenses paid or reimbursed for such services, including any clinical study payments, meal or 
travel expenses or reimbursements, consulting fees, and any other transfer of value. 


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18.
APPENDIX
18.1.
Appendix 1:  Revised International Working Group Response Criteria for 
Malignant Lymphoma
Information in this section has been taken from {Cheson 2007}. These criteria will be used for 
disease assessments by the site investigators for subjects in Cohort 1 only.
18.1.1.
Complete Response
Complete response (CR) requires all of the following: 

Complete disappearance of all detectable clinical evidence of disease and disease-related 
symptoms if present before therapy. 

Typically fluorodeoxyglucose (FDG)-avid lymphoma (large cell, mantle cell, and follicular 
lymphomas are all typically FDG-avid):  In subjects with no pre-treatment positron emission 
tomography (PET) scan or when the PET scan was positive before therapy, a post-treatment 
residual mass of any size is permitted as long as it is PET negative.  

Variably FDG-avid lymphomas/FDG avidity unknown:  In subjects without a pre-treatment 
PET scan or if a pre-treatment PET scan was negative, all lymph nodes and nodal masses 
must have regressed to normal size (≤ 1.5 cm in greatest diameter if > 1.5 cm before 
therapy).  Previously involved nodes that were 1.1 to 1.5 cm in their long axis and more than 
1 cm in their short axis before treatment must have decreased to ≤ 1.0 cm in their short axis 
after treatment.  

The spleen and/or liver, if considered to be enlarged before therapy on basis of physical exam 
or CT scan, should be normal size on CT scan and not be palpable on physical examination, 
and nodules thought to represent lymphoma must no longer be present.  

A bone marrow aspirate and biopsy is performed only when the patient had bone marrow 
involvement with lymphoma prior to therapy or if new abnormalities in the peripheral blood 
counts or blood smear cause clinical suspicion of bone marrow involvement with lymphoma 
after treatment.  The bone marrow aspirate and biopsy must show no evidence of disease by 
morphology, or, if indeterminate by morphology, it must be negative by 
immunohistochemistry.  The biopsy core sample must be a minimum of 20 mm in length. 
18.1.2.
Partial Response
A partial response (PR) requires all of the following:

≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest 
dominant nodes or nodal masses.  Dominant nodes or nodal masses should be clearly 
measurable in at least 2 perpendicular dimensions, should be from different regions of the 
body if possible, and should include mediastinal and retroperitoneal nodes if possible.  


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
No increase in size of nodes, liver, or spleen and no new sites of disease.  

If multiple splenic and hepatic nodules are present, they must regress by ≥ 50% in the SPD.  
There must be a > 50% decrease in the greatest transverse diameter for single nodules.   

Bone marrow is irrelevant for determination of a PR.  If subject has persistent bone marrow 
involvement and otherwise meets criteria for CR, then the subject will be considered a PR.

Typically FDG-avid lymphoma:  for subjects with no pre-treatment PET scan or if the PET 
scan was positive before therapy, the post-treatment PET scan should be positive in at least 
1 previously involved site.  Note:  in subjects with follicular lymphoma or mantle cell 
lymphoma, a PET scan is only indicated in subjects with 1 or at most 2 residual masses that 
have regressed by 50% on CT scan.
18.1.3.
Stable Disease
Stable disease (SD) requires: 

Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for 
progressive disease.  PET should be positive in typically FDG-avid lymphomas.
18.1.4.
Progressive Disease
Progressive disease (PD) is defined by at least one of the following:  

≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes, or, if a single 
node is involved, at least a 50% increase in the product of the diameters of this 1 node  

Appearance of a new lesion > 1.5 cm in any axis even if other lesions are decreasing in size

≥ 50% increase in size of splenic or hepatic nodules 

At least a 50% increase in the longest diameter of any single previously identified node more 
than 1 cm in its short axis

Lesions should be PET positive in typically FDG-avid lymphomas unless the lesion is too 
small to be detected by PET (< 1.5 cm in its long axis by CT).


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18.2.
Appendix 2:  Lugano Classification
18.2.1.
Disease Staging
Subjects in Cohort 3 will have disease staging at study entry performed per the Lugano 
Classification {Cheson 2014}. This staging system is a modification of the Ann Arbor 
classification and is presented in Table 11.
Table 11.
Disease Staging System per Cheson, 2014
Stage
Involvement
Extranodal (E) Status
Limited
I
One node or a group of adjacent nodes
Single extranodal lesions without nodal 
involvement
II
Two or more nodal groups on the same 
side of the diaphragm
Stage I or II by nodal extent with 
limited contiguous extranodal 
involvement
II bulkya
II as above with “bulky” disease
Not applicable
Advanced
III
Nodes on both sides of the diaphragm; 
nodes above the diaphragm with spleen 
involvement
Not applicable
IV
Additional noncontiguous 
extralymphatic involvement
Not applicable 
Note: Tonsils, Waldeyer’s ring, and spleen are considered nodal tissue.
a
Whether stage II bulky disease is treated as limited or advanced disease may be determined by histology and prognostic 
factors.
18.2.2.
Disease Response Assessment
Refer to imaging manual and {Cheson 2014} for details of assessment. These criteria will be 
used for disease assessments by the site investigators for subjects in Cohort 2 and Cohort 3.
Table 12.
5-point Scale (5PS)
Score
Description
1
No uptake above background
2
Uptake ≤ mediastinum
3
Uptake > mediastinum but ≤ liver
4
Uptake moderately higher than liver
5
Uptake markedly higher than liver and/or new lesions
X
New areas of uptake unlikely to be related to lymphoma
From {Barrington 2014} 


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18.2.2.1.
Complete Response
18.2.2.1.1.
Complete Metabolic Response 
The designation of complete metabolic response (CMR) for PET-CT-based response requires all 
of the following:

A 5-point scale (5PS) score of 1, 2, or 3, with or without a residual mass
In Waldeyer’s ring or extranodal sites with high physiologic uptake or with activation 
within spleen or marrow, uptake may be greater than normal mediastinum and/or liver.  
In this circumstance, CMR may be inferred if uptake at sites of initial involvement is no 
greater than surrounding normal tissue even if the tissue has high physiologic uptake.

No new sites of disease should be observed.
18.2.2.1.2.
Complete Radiologic Response 
The designation of complete radiologic response (CRR) for CT-based response requires all of the 
following:

Target nodes/nodal masses must regress to ≤ 1.5 cm in longest transverse diameter of a lesion 
(LDi).

No extralymphatic sites of disease

Absent non-measured lesion

Organ enlargement regress to normal (eg, an enlarged spleen at baseline must be ≤ 13 cm at 
assessment)

No new sites of disease should be observed.

Bone marrow normal by morphology; if indeterminate, immunohistochemistry negative 
18.2.2.2.
Partial Response
18.2.2.2.1.
Partial Metabolic Response
The designation of partial metabolic response (PMR) for PET-CT-based response requires all of 
the following:

A 5PS score of 4 or 5, with reduced uptake compared to baseline (screening), and residual 
mass(es) of any size

Note:
At interim, these findings suggest responding disease.
At end of treatment, these findings suggest residual disease.

No new sites of disease should be observed.


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If there are persistent focal changes in the marrow in the context of a nodal response, 
consideration should be given to further evaluation with magnetic resonance imaging or biopsy 
or an interval scan.
18.2.2.2.2.
Partial Radiologic Response
The designation of partial radiologic response (PRR) for CT-based response requires all of the 
following:

≥ 50% decrease in the SPD of up to 6 target measurable nodes and extra-nodal sites
When a lesion is too small to measure by CT, assign 5 mm x 5 mm as the default value.
For a node > 5 mm x 5 mm, but smaller than normal, use actual measurements for 
calculation.

Absent/normal, regressed, but no increase of non-measured lesions

Spleen must have regressed by > 50% in length beyond normal (ie, ≤ 13 cm).  For example, 
if the spleen is 15 cm at baseline, it must be ≤ 14 cm at assessment to classify as a PRR. 
18.2.2.3.
Stable Disease
18.2.2.3.1.
No Metabolic Response
The designation of no metabolic response (NMR) for PET-CT-based response requires all of the 
following:

A 5PS score of 4 or 5, with no significant change in FDG uptake compared to baseline 
(screening), at an interim time point or end of treatment

No new sites of disease should be observed.
18.2.2.3.2.
Stable Radiologic Disease
The designation of stable radiologic disease (SRD) for CT-based response requires all of the 
following:

< 50% decrease from baseline in the SPD of up to 6 dominant, measurable nodes and extra-
nodal sites; no criteria for progressive disease (PD) are met

No increase consistent with progression in non-measured lesion and organ enlargement

No new sites of disease should be observed.


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18.2.2.4.
PD
18.2.2.4.1.
Progressive Metabolic Disease
The designation of progressive metabolic disease (PMD) for PET-CT-based response requires at 
least 1 of the following:

A 5PS score 4 or 5 with an increase in intensity of uptake from baseline, and/or

New FDG-avid foci consistent with lymphoma at interim or end of treatment assessment

New FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, 
inflammation).  If uncertain regarding etiology of new lesions, biopsy or interval scan may be 
considered.

New or recurrent FDG-avid foci in bone marrow.
18.2.2.4.2.
Progressive Radiologic Disease
The designation of progressive radiologic disease (PRD) for CT-based response requires at least 
1 of the following:

An individual node/lesion must be abnormal with:
LDi > 1.5 cm, and
Increase by ≥ 50% from cross-product of LDi and perpendicular diameter (PPD) nadir, and
An increase in LDi or shortest axis perpendicular to the LDi from nadir
■
0.5 cm for lesions ≤ 2 cm
■
1.0 cm for lesions > 2 cm
In the setting of splenomegaly, the splenic length must increase by > 50% of the extent of 
its prior increase beyond baseline (eg, a 15 cm spleen must increase to > 16 cm).  If no 
prior splenomegaly, the increase must be ≥ 2 cm from baseline;
New or recurrent splenomegaly

New or clear progression of pre-existing non-measured lesions

New lesion
Regrowth of previously resolved lesions
A new node > 1.5 cm in any axis
A new extra-nodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be 
unequivocal and must be attributable to lymphoma
Assessable disease of any size unequivocally attributable to lymphoma

New or recurrent bone marrow involvement


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18.3.
Appendix 3:  Monitoring of Subjects After IP Administration per Country 
Regulatory Agencies 
Germany, France, and United Kingdom:
The post-infusion monitoring of subjects, described in Section 7.12.6.2 in this protocol, will be 
extended by monitoring on Day 8, Day 9, and Day 10, according to procedures outlined in 
Table 7 or Table 9, column “IP administration period, 1-7.” The subject may stay hospitalized or 
return to the clinic daily for this extended monitoring at the discretion of the investigator. 


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18.4.
Appendix 4: Cytokine Release Syndrome Grading per Lee, 2014
For all subjects, the severity of cytokine release syndrome (CRS) will be graded according to the 
grading system proposed by Lee and colleagues {Lee 2014} (Table 13). Guidelines for 
management of CRS are provided in the current Investigator’s Brochure (IB).  
Table 13.
CRS Grading Scale (Excluding Neurologic Events) per Lee, 2014
Grade
Symptoms
Grade 1
Symptoms are not life-threatening and require symptomatic treatment only (eg, fever, nausea, 
fatigue, headache, myalgia, malaise)
Grade 2
Symptoms require and respond to moderate intervention 
Oxygen requirement < 40% FiO2 or 
Hypotension responsive to fluids or low dose of 1 vasopressora or 
Grade 2 organ toxicityb
Grade 3
Symptoms require and respond to aggressive intervention
Oxygen requirement ≥ 40% FiO2 or
Hypotension requiring high-dose or multiple vasopressorsa or 
Grade 3 organ toxicity or Grade 4 transaminitisb
Grade 4
Life-threatening symptoms
Requirements for ventilator support or
Grade 4 organ toxicity (excluding transaminitis)b
Grade 5
Death
Abbreviations: CRS, cytokine release syndrome; FiO2, fraction of inspired oxygen.
a
High-dose vasopressor doses shown in Table 14.
b
Severity based on Common Terminology Criteria for Adverse Events.
Table 14.
Definitions of High-dose Vasopressors in Adults
Vasopressor
Dosea
Norepinephrine monotherapy
≥ 20 µg/min
Dopamine monotherapy
≥ 10 µg/kg/min
Phenylephrine monotherapy
≥ 200 µg/min
Epinephrine monotherapy
≥ 10 µg/min
If on vasopressin 
Vasopressin + norepinephrine equivalent of ≥ 10 µg/minb
If on combination vasopressors 
(not vasopressin)
Norepinephrine equivalent of ≥ 20 µg/minb
a
All doses are required for ≥ 3 hours.
b
VASST Trial vasopressor equivalent equation: norepinephrine equivalent dose = [norepinephrine (µg/min)] 
+ [dopamine (µg/kg/min) ÷ 2] + [epinephrine (µg/min)] + [phenylephrine (µg/min) ÷ 10]


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18.5.
Appendix 5: Cytokine Release Syndrome Grading per American Society for 
Transplantation and Cellular Therapy
In 2018, the American Society for Transplantation and Cellular Therapy (ASTCT) published a 
grading system for cytokine release syndrome (CRS) {Lee 2019}. For subjects in Cohort 3 only, 
in addition to the modified Lee criteria (Section 18.4), CRS will also be assessed by ASTCT 
grading, as shown in Table 15. Importantly, toxicity management will only be based on Kite 
grading and management criteria as described in the current Investigator’s Brochure (IB).
Table 15.
ASTCT CRS Consensus Grading
CRS parameter
Grade 1
Grade 2
Grade 3
Grade 4
Fevera
Temperature ≥ 38°C
Temperature ≥ 38°C
Temperature ≥ 38°C
Temperature ≥ 38°C
With
Hypotension
None
Not requiring 
vasopressors
Requiring a vasopressor 
with or without 
vasopressin
Requiring multiple 
vasopressors (excluding 
vasopressin)
And/orb
Hypoxia
None
Requiring low-flow 
nasal cannulac or 
blow-by
Requiring high-flow 
nasal cannulac, 
facemask, nonrebreather 
mask, or Venturi mask
Requiring positive 
pressure (eg, CPAP, 
BiPAP, intubation and 
mechanical ventilation)
Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; BiPAP, bilevel positive airway pressure; 
CPAP, continuous positive airway pressure; CRS, cytokine release syndrome.
Notes: Organ toxicities associated with CRS may be graded according to the Common Terminology Criteria for Adverse Events 
but they do not influence CRS grading.
a
Fever is defined as temperature ≥ 38°C not attributable to any other cause. In patients who have CRS then receive 
antipyretic or anticytokine therapy such as tocilizumab or corticosteroids, fever is no longer required to grade subsequent 
CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia.
b
The CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a patient with temperature of 39.5° C, hypotension requiring 1 vasopressor, and hypoxia requiring low-flow nasal 
cannula is classified as Grade 3 CRS.
c
Low-flow nasal cannula is defined as oxygen delivered at ≤ 6 L/minute. Low flow also includes blow-by oxygen delivery, 
sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at > 6 L/minute.


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18.6.
Appendix 6: Neurologic Event Grading per American Society for 
Transplantation and Cellular Therapy
In 2018, the American Society for Transplantation and Cellular Therapy (ASTCT) published a 
grading system for immune effector cell-associated neurotoxicity syndrome (ICANS) {Lee 
2019}. For subjects in Cohort 3 only, ICANS will be assessed by the ASTCT grading, as shown 
in Table 16 (using immune effector cell-associated encephalopathy [ICE] scores as determined 
by Table 17). However, neurotoxicity management will only be based on the Common 
Terminology Criteria for Adverse Events (CTCAE) grading as described in the current 
Investigator’s Brochure (IB).
Table 16.
ASTCT ICANS Consensus Grading for Adults
Neurotoxicity 
Domain
Grade 1
Grade 2
Grade 3
Grade 4
ICE scorea
7 to 9
3 to 6
0 to 2
0 (patient is unarousable and 
unable to perform ICE)
Depressed level of 
consciousnessb
Awakens 
spontaneously
Awakens to 
voice
Awakens only to tactile 
stimulus
Patient is unarousable or requires 
vigorous or repetitive tactile 
stimuli to arouse.
Stupor or coma
Seizure
N/A
N/A
Any clinical seizure focal 
or generalized that resolved 
rapidly or nonconvulsive 
seizures on EEG that 
resolve with intervention
Life-threatening prolonged 
seizure (> 5 min); or
Repetitive clinical or electrical 
seizures without return to 
baseline in between
Motor findingsc
N/A
N/A
N/A
Deep focal motor weakness such 
as hemiparesis or paraparesis
Elevated ICP/ 
cerebral edema
N/A
N/A
Focal/local edema on 
neuroimagingd
Diffuse cerebral edema on 
neuroimaging; decerebrate or 
decorticate posturing; or cranial 
nerve VI palsy; or papilledema; 
or Cushing's triad
Abbreviation: ASTCT, American Society for Transplantation and Cellular Therapy; CTCAE, Common Terminology Criteria for 
Adverse Events; EEG, electroencephalogram; ICANS, immune effector cell-associated neurotoxicity syndrome; ICE, immune 
effector cell-associated encephalopathy; ICP, intracranial pressure; N/A, not applicable.
Notes: The ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, and 
raised ICP/cerebral edema) not attributable to any other cause; for example, a patient with an ICE score of 3 who has a 
generalized seizure is classified with Grade 3 ICANS.
a
A patient with an ICE score of 0 may be classified with Grade 3 ICANS if awake with global aphasia, but a patient with an 
ICE score of 0 may be classified with Grade 4 ICANS if unarousable.
b
Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication).
c
Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE, but they do not 
influence the ICANS grading.
d
Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded from 
ICANS grading. It may be graded according to CTCAE.


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Table 17.
Immune Effector Cell-associated Encephalopathy Scorea
Task
Score
Orientation:
Orientation to year, month, city, hospital 
4 points
Naming:
Ability to name 3 objects 
(eg, point to clock, pen, button) 
3 points
Following commands:
Ability to follow simple commands
(eg, “Show me 2 fingers” or “Close your eyes and stick out your tongue”) 
1 point
Writing:
Ability to write a standard sentence 
(eg, “Our national bird is the bald eagle”) 
1 point
Attention:
Ability to count backwards from 100 by 10 
1 point
a
Immune effector cell-associated encephalopathy (ICE) score as developed by the American Society for Transplantation and 
Cellular Therapy consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector 
cells {Lee 2019}.


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18.7.
Appendix 7: Childbearing Potential and Birth Control 
This study will follow the recommendations from the Clinical Trial Facilitation Group (CTFG) 
{Clinical Trials Facilitation Group (CTFG) 2014}, as described in the following sections. 
18.7.1.
Definition of Childbearing Potential
A female is considered of childbearing potential (ie, fertile) following menarche and until 
becoming postmenopausal unless permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used 
to confirm a postmenopausal state in females not using hormonal contraception or hormonal 
replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient.
For the purpose of this study, a male is considered fertile after puberty unless permanently sterile 
by bilateral orchidectomy.
18.7.2.
Birth Control Methods That May Be Considered as Highly Effective
Methods that can achieve a failure rate of < 1% per year when used consistently and correctly are 
considered as highly effective birth control methods. Such methods include: 

Combined (estrogen- and progesterone-containing) hormonal contraception associated with 
inhibition of ovulationa:
Oral
Intravaginal
Transdermal

Progestogen-only hormonal contraception associated with inhibition of ovulationa:
Oral
Injectable
Implantableb

Intrauterine device (IUD)b
a  Hormonal contraception may be susceptible to interaction with the investigational product, which may reduce the 
efficacy of the contraception method.
b  Contraception methods that in the context of this guidance are considered to have low user dependency.


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
Intrauterine hormone-releasing system (IUS)b

Bilateral tubal occlusionb

Vasectomized partnerb,c

Sexual abstinenced
18.7.3.
Unacceptable Birth Control Methods 
Birth control methods that are unacceptable include periodic abstinence (calendar, 
symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and 
lactational amenorrhoea method (LAM). A female condom and a male condom should not be 
used together.
c  A vasectomized partner is a highly effective birth control method provided that the partner is the sole sexual 
partner of the female of childbearing potential trial participant and that the vasectomized partner has received 
medical assessment of the surgical success.
d  In the context of this guidance sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and preferred 
and usual lifestyle of the subject.


amd-9-protocol KTE-C19-102
ELECTRONIC SIGNATURES
Signed by
Meaning of Signature
Server Date
(dd-MMM-
yyyy hh:mm:ss)
Clinical eSigned
10-Nov-2022
15:48:39
PPD-

SAP_003.pdf: 
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Product Name:
KTE-X19
Protocol:
A Phase 2 Multicenter Study Evaluating the Efficacy of 
KTE-X19 in Subjects with Relapsed/Refractory Mantle Cell 
Lymphoma (ZUMA-2)
Version Number:
Version 7.0
Release Date:
09 February 2022
Replaces Previous Version(s):
Version 6.0; dated 08 July 2019
CONFIDENTIALITY NOTICE
This document contains confidential information of Kite Pharma Inc., a wholly owned subsidiary 
of Gilead Sciences Inc.  This document must not be disclosed to anyone other than the site 
research staff and members of the Institutional Review Board/Independent Ethics Committee, a 
scientific review board or an equivalent.  The information in this document cannot be used for 
any purpose other than the conduct of the clinical investigation without the prior written consent 
of Kite Pharma Inc.  Questions regarding how this document should be used or the conduct of 
the clinical trial should be directed to the key sponsor contacts.


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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF TABLES..........................................................................................................................................................4
LIST OF ABBREVIATIONS.........................................................................................................................................5
1.
INTRODUCTION..................................................................................................................................................7
2.
OBJECTIVES.........................................................................................................................................................8
3.
STUDY OVERVIEW ............................................................................................................................................9
3.1.
Study Design .............................................................................................................................................9
3.2.
Hypothesis ...............................................................................................................................................11
3.3.
Sample Size Considerations ....................................................................................................................11
3.4.
Statistical Assumptions ...........................................................................................................................14
4.
STUDY ENDPOINTS AND COVARIATES......................................................................................................15
4.1.
Endpoints.................................................................................................................................................15
4.1.1.
Primary ..................................................................................................................................15
4.1.2.
Secondary ..............................................................................................................................15
4.1.3.
Exploratory............................................................................................................................15
4.2.
Covariates................................................................................................................................................16
4.2.1.
Baseline Covariates ...............................................................................................................16
4.2.2.
Tocilizumab and Steroid use after Anti-CD19 CAR T Cells Infusion..................................17
5.
DEFINITIONS .....................................................................................................................................................18
5.1.
General ....................................................................................................................................................18
5.2.
Safety.......................................................................................................................................................19
5.3.
Efficacy....................................................................................................................................................20
6.
ANALYSIS SETS................................................................................................................................................22
6.1.
Modified Intent-to-treat...........................................................................................................................22
6.2.
Inferential Analysis Set ...........................................................................................................................22
6.3.
Safety Analysis Set..................................................................................................................................22
6.4.
Full Analysis Set......................................................................................................................................22
6.5.
mITT Retreatment Analysis Set ..............................................................................................................22
6.6.
Safety Retreatment Analysis Set .............................................................................................................22
6.7.
Subgroup Analysis Sets...........................................................................................................................22
7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES....................................................................23
7.1.
Interim Analysis ......................................................................................................................................23
7.2.
Assessment of Criteria to Pause Enrollment ...........................................................................................23
7.3.
Access to Aggregate and Subject-level Data and Individual Subject Treatment Assignments ..............24
8.
DATA SCREENING AND ACCEPTANCE.......................................................................................................26
8.1.
General Principles ...................................................................................................................................26
8.2.
Electronic Transfer and Archival of Data ...............................................................................................26
8.3.
Handling of Missing and Incomplete Data..............................................................................................26
8.3.1.
Efficacy..................................................................................................................................26
8.3.2.
Safety.....................................................................................................................................26
8.4.
Detection of Bias .....................................................................................................................................27
8.5.
Outliers ....................................................................................................................................................27
8.6.
Distributional Characteristics ..................................................................................................................27


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8.7.
Validation and Configuration Management ............................................................................................27
9.
STATISTICAL METHODS OF ANALYSIS......................................................................................................28
9.1.
General Principles ...................................................................................................................................28
9.2.
Subject Accountability ............................................................................................................................28
9.3.
Important Protocol Deviations ................................................................................................................28
9.4.
Demographic and Baseline Characteristics.............................................................................................28
9.5.
Efficacy Analyses....................................................................................................................................29
9.5.1.
ORR and Best Response........................................................................................................30
9.5.2.
DOR.......................................................................................................................................30
9.5.3.
PFS ........................................................................................................................................31
9.5.4.
OS..........................................................................................................................................31
9.5.5.
Tumor Burden .......................................................................................................................31
9.5.6.
Objective Response and Best Response Among Subjects Retreated with 
Anti-CD19 CAR T Cells.......................................................................................................32
9.5.7.
DORR....................................................................................................................................32
9.5.8.
Incidence of SCT...................................................................................................................32
9.5.9.
European Quality of Life-5 Dimensions and Visual Analogue Scale 
Scores ....................................................................................................................................32
9.5.10.
European Organization for Research and Treatment of Cancer Quality of 
Life Questionnaire (EORTC-QLQ-C30) scores....................................................................32
9.6.
Safety Analyses .......................................................................................................................................32
9.6.1.
AEs ........................................................................................................................................33
9.6.2.
Procedures and Concomitant Medications ............................................................................34
9.6.3.
Laboratory Test Results.........................................................................................................34
9.6.4.
Anti-CD19 CAR Antibodies .................................................................................................34
9.6.5.
RCR.......................................................................................................................................34
9.6.6.
Exposure to Study Treatment ................................................................................................34
9.6.7.
Exposure to Concomitant Medications and Procedures........................................................35
9.6.8.
Mini-mental Status Exam or Immune Effector Cell-associated 
Encephalopathy .....................................................................................................................35
9.7.
Subsequent Anti-cancer Therapy ............................................................................................................35
9.8.
Schedule of Study Treatment ..................................................................................................................35
9.9.
CAR T Cells Measured in Peripheral Blood ...........................................................................................36
9.10.
B-cell Aplasia ..........................................................................................................................................36
10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES..............................................................................37
11.
REFERENCES.....................................................................................................................................................38
12.
HISTORY OF REVISIONS.................................................................................................................................39
13.
APPENDICES......................................................................................................................................................42
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates ...........42
Appendix 2.
Sample Adverse Event Table Layouts.....................................................................................44
Appendix 3.
Derivation of Time to Event Endpoints and Last Date Known to Be Alive ...........................45
Appendix 4.
Derivation of Simplified Mantle Cell Lymphoma International Prognostic Index.................50


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LIST OF TABLES
Table 1.
Imputation Rules for Partial or Missing Start Dates................................................................42
Table 2.
Subject Incidence of <AE Descriptor> AEs by Preferred Term (Worst Grade).....................44
Table 3.
Subject Incidence of <AE Descriptor> AEs by System Organ Class and Preferred 
Term (Worst Grade) ................................................................................................................44
Table 4.
Primary Analysis of DOR........................................................................................................45
Table 5.
Sensitivity Analysis of DOR (to include data after SCT post study treatment)......................46
Table 6.
Primary Analysis of PFS .........................................................................................................47
Table 7.
Sensitivity Analysis of PFS .....................................................................................................47
Table 8.
Analysis of OS.........................................................................................................................48
Table 9.
Simplified Mantle Cell Lymphoma International Prognostic Index .......................................50
Table 10.
Risk Category Based on s-MIPI ..............................................................................................50


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LIST OF ABBREVIATIONS 
ADaM
Analysis data model
AE
Adverse event
Allo-SCT
Allogeneic stem cell transplant
Auto-SCT
Autologous stem cell transplant
CAR
Chimeric antigen receptor
CIF
Cumulative incidence 
CR
Complete response
CRS
Cytokine release syndrome
CTCAE
Common Terminology Criteria for Adverse Event
DOR
Duration of response
DORR
Duration of response to retreatment
DSMB
Data Safety Monitoring Board
ECOG
Eastern Cooperative Oncology Group
EQ-5D
European quality of life-5 dimensions
EORTC-QLQ
European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire
FAS
Full analysis set
HLGT
High-level group term
ICANS
Immune effector cell-associated neurotoxicity syndrome
IRRC
Independent Radiology Review Committee
MCL
Mantle cell lymphoma 
mITT
Modified intent-to-treat
MedDRA
Medical Dictionary for Regulatory Activities
NE
Not evaluable
OS
Overall survival
PD
Progressive disease
PFS
Progression-free survival
PR
Partial response
RCR
Replication-competent retrovirus
r/r MCL
Relapsed/refractory mantle cell lymphoma
SAE
Serious adverse event
SCT
Stem cell transplant
SD
Stable disease
SDTM
Study data tabulation model 
SMQ
Standardized MedDRA query 
s-MIPI
Simplified Mantle Cell Lymphoma International Prognostic Index 
SOC
System organ class
SPD
Sum of the product of the diameter
SSC
Scientific steering committee
TEAE
Treatment-emergent adverse event


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TLS
Tumor lysis syndrome
VAS
Visual analogue scale


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1.
INTRODUCTION 
This statistical analysis plan provides the pre-specification and details for the statistical analyses 
outlined within protocol KTE-C19-102, amendment 8.0 (Date: 10 Dec 2021) entitled “A Phase 2 
Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects with Relapsed/Refractory 
Mantle Cell Lymphoma (ZUMA-2).”  The scope of this document is to provide details on the 
planned interim, primary, and final analyses.


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2.
OBJECTIVES
The primary objective is to evaluate the efficacy of KTE-X19, as measured by objective response rate 
(ORR), in subjects with relapsed/refractory (r/r) mantle cell lymphoma (MCL).  Secondary objectives 
include assessing the safety and tolerability of KTE-X19 and additional efficacy endpoints including 
duration of response (DOR). Secondary objectives related to patient-reported outcomes (PROs) in 
Cohort 1 and Cohort 2 will include change in the European Quality of Life-5 Dimensions (EQ-
5D) scores from baseline to Month 6. Secondary objectives related to PROs in Cohort 3 will 
include change in EQ-5D and European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire (EORTC-QLQ-C30) scores from baseline over time.


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3.
STUDY OVERVIEW
3.1.
Study Design
Study KTE-C19-102 is a multicenter, open-label Phase 2 study evaluating the safety and efficacy 
of KTE-X19 in subjects with r/r MCL.  
This study is designed to examine the safety and efficacy of KTE-X19in patients who have r/r 
MCL that has progressed on prior chemotherapy and anti-CD20 antibody therapy with or 
without ibrutinib or acalabrutinib. The study will evaluate the ORR and durability of response 
after treatment with KTE-X19. An open-label, 3-cohort design is used, with the following 
cohorts: 
•
Cohort 1 and Cohort 2 will include subjects with r/r MCL who have been treated with up 
to 5 prior regimens including a BTKi. Prior therapy must have included all of the 
following: anthracycline or bendamustine-containing chemotherapy, anti-CD20 
monoclonal antibody therapy, and ibrutinib or acalabrutinib. 
•
Cohort 3 will include subjects with r/r MCL who have been treated with up to 5 prior 
regimens but have not received prior therapy with a BTKi. Prior therapy must have 
included anthracycline, bendamustine, or high-dose cytarabine containing chemotherapy 
and anti-CD20 monoclonal antibody therapy.
Up to approximately 220 subjects with r/r MCL in total will be enrolled and treated to evaluate 
the efficacy of KTE-X19:
•
Cohort 1 will treat up to approximately 90 subjects at a target dose of 2x106 anti-CD19 
CAR T cells/kg, including up to approximately 80 KTE-X19 subjects and 10 
axicabtagene ciloleucel subjects. The Cohort 1 KTE-X19 subjects will form the basis for 
statistical hypothesis testing on the primary end point in Cohort 1, with a target ORR in 
the alternative hypothesis of 50% and a futility criterion that the ORR is no more than 
25%. As of 28May2019, Cohort 1 has completed enrollment. 
•
Cohort 2 will treat up to 40 KTE-X19 subjects at a target dose of 0.5 x 106 anti-CD19 
CAR T cells/kg. As of 01May2018, Cohort 2 has completed enrollment. 
•
Cohort 3 will enroll and treat up to approximately 90 KTE-X19 subjects at a target dose 
of 2x106 anti-CD19 CAR T cells/kg, forming the basis for statistical hypothesis testing on 
the primary end point in Cohort 1 with a target ORR in the alternative hypothesis of 75% 
and a null hypothesis that the ORR is 57% or less.


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Each subject will proceed through the following study periods:
•
Screening 
•
Enrollment/Leukapheresis 
•
Bridging therapy, if applicable
•
Conditioning chemotherapy 
•
Investigational product treatment 
•
Post-treatment assessment 
•
Long-term follow-up 
Additional details on study procedures may be found in the study protocol.  
An independent Data Safety Monitoring Board (DSMB) will meet and review safety and/or 
efficacy data for Cohort 1 and Cohort 2 at 4 times during the study:
For Cohort 1:  The DSMB will first meet to review safety data when 10 subjects have been 
treated with anti-CD19 CAR T cells and have been followed for 30 days.  The DSMB will meet 
for the second time to review both safety and efficacy data after 20 subjects have been treated 
with anti-CD19 CAR T cells and have had the opportunity to complete the 3-month disease 
assessment. The DSMB will review safety again after 44 subjects in Cohort 1 have been treated 
with anti-CD19 CAR T cells and have had opportunity to be followed for at least 30 days after 
the anti-CD19 CAR T cells infusion, with focus on the safety data from the 6 KTE-X19 subjects 
treated most recently within this cohort. 
For Cohort 2:  The DSMB will meet to review both safety and efficacy data after 10 subjects 
have been treated with KTE-X19 and have had the opportunity to be followed for 30 days.
The DSMB will be chartered to make trial conduct recommendations for Cohort 1 and Cohort 2 
based on an analysis of risk vs benefit.  The DSMB may meet more often as needed. 
For Cohort 3: A Scientific Steering Committee (SSC), comprising the study sponsor and at least 
3 study investigators, will be specifically chartered to review the safety data from Cohort 3 and 
make recommendations on further study conduct. The SSC will meet after 15 subjects in Cohort 
3 have been enrolled, treated with KTE-X19, and have had the opportunity to be followed for 30 
days, and again after 50 subjects in Cohort 3 have been enrolled, treated with KTE-X19, and 
have had the opportunity to be followed for 3 months. The SSC may meet more often as needed.  
There will be an additional interim analysis for Cohort 1 after 38 subjects treated with anti-CD19 
CAR T cells in Cohort 1 have had the opportunity to be evaluated for response 6 months after the 
anti-CD19 CAR T cells infusion.  This interim analysis will be performed for a Kite Pharma, 


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Inc., (hereafter referred to as Kite or Kite Pharma) internal review of the accumulating data of 
safety and efficacy.  
The primary analysis in Cohort 1 and Cohort 2 will occur after 60 KTE-X19 subjects have been 
enrolled and treated in Cohort 1 and have had the opportunity to be evaluated for response 6 
months after the Week 4 disease assessment (see details in Section 3.3).
The primary analysis in Cohort 3 will occur after 86 subjects in Cohort 3 have been enrolled and 
treated with KTE-X19 and have had the opportunity to be assessed for response 6 months after 
the first objective response or 9 months after the KTE-X19 infusion, whichever is earlier (see 
details in Section 3.3).
The primary analysis of efficacy endpoints will be based on the Lugano Classification {Cheson 
2014} per Independent Radiology Review Committee (IRRC) review for all cohorts.  These 
assessments will be referred to as “Central Read” in this document.  Secondary efficacy analyses 
will be based on investigator review of disease assessments, henceforth referred to as 
“Investigator Read.”  For Cohort 1, the Investigator Read will be based on the revised 
International Working Group Criteria for Malignant Lymphoma {Cheson 2007}; for Cohort 2 
and Cohort 3, the Investigator Read will be based on the Lugano Classification {Cheson 2014}.   
3.2.
Hypothesis
An alternative hypothesis will be tested among Cohort 1 KTE-X19 subjects with a target 50% 
ORR per independent review against a null hypothesis that the ORR is 25% or less.  The 
hypothesis is that the ORR to KTE-X19 in Cohort 1 KTE-X19 subjects is significantly greater 
than 25%. 
For Cohort 3, an alternative hypothesis will be tested with a target 75% ORR per independent 
review against a null hypothesis that the ORR is 57% or less. The hypothesis is that the ORR to 
KTE-X19 per independent review is significantly greater than 57% in Cohort 3 subjects.
3.3.
Sample Size Considerations
This study uses an open-label 3-cohort design to test for an improvement in ORR. Up to 
approximately 220 subjects with r/r MCL will be enrolled and treated with anti-CD19 CAR T 
cells, including 10 axicabtagene ciloleucel subjects and up to approximately 80 KTE-X19 
subjects in Cohort 1, up to approximately 40 KTE-X19 subjects in Cohort 2 and up to 
approximately 90 KTE-X19 subjects in Cohort 3.  
Hypothesis testing of the primary endpoint ORR will be conducted on Cohort 1 inferential 
analysis set.  Primary analysis in Cohort 1 will be conducted after 60 KTE-X19 subjects have 
been enrolled and treated and have had the opportunity to be assessed for response 6 months 
after the Week 4 disease assessment. A sample size of 60 KTE-X19 subjects in Cohort 1 


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provides at least 96% power to distinguish between an active therapy with a 50% true response 
rate from a therapy with a response rate of 25% or less, with a 1-sided alpha level of 0.025. 
The primary analysis in Cohort 3 will be conducted after 86 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be assessed for response 6 
months after the first objective response or 9 months after the KTE-X19 infusion, whichever is 
earlier. For the test of efficacy in Cohort 3, a sample size of 86 subjects will provide at least 90% 
power to distinguish between an active therapy with a 75% true response rate and a therapy with 
a response rate of 57% or less with a 1-sided alpha level of 0.025.
Four interim analyses in Cohort 1 and one interim analysis in Cohort 2 will be performed: 
•
Cohort 1 interim analysis 1 will be conducted after 10 subjects have been treated with 
anti-CD19 CAR T cells and have been followed for 30 days.  In this interim analysis, the 
DSMB will review data for safety only. 
•
Cohort 1 interim analysis 2 will be conducted after 20 subjects have had the opportunity to be 
evaluated for response 3 months after treatment with anti-CD19 CAR T cells.  In this interim 
analysis, the DSMB will review data for both safety and efficacy (futility only). 
•
Cohort 1 interim analysis 3 will occur after all the 38 treated subjects in this cohort have had 
the opportunity to be evaluated for response 6 months after anti-CD19 CAR T cells infusion.  
This interim analysis will be performed for a Kite internal review of the accumulating data of 
safety and efficacy.
•
Cohort 1 interim analysis 4 will occur after 44 subjects in Cohort 1 have been treated with 
anti-CD19 CAR T cells and have had the opportunity to be followed for 30 days after 
anti-CD19 CAR T cells infusion.  In this interim analysis, the DSMB will review data for 
safety only, with focus on the 6 KTE-X19 subjects treated most recently in this cohort.
•
Cohort 2 interim analysis will occur after 10 subjects in this cohort have been enrolled and 
treated with KTE-X19 and have had the opportunity to be followed for 30 days after 
KTE-X19 infusion.  This interim analysis will be for safety and efficacy. 
In Cohort 3, two interim analyses will be performed for safety only: 
•
Cohort 3 interim analysis 1 will be conducted after 15 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed for 30 days 
after the KTE-X19 infusion. 
•
Cohort 3 interim analysis 2 will be conducted after 50 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed for 3 
months after the KTE-X19 infusion. 
Accrual to and treatment on the study will continue during all interim analyses.  


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Two primary analyses for the study will be performed, followed by long-term follow-up analyses 
as described below:
One primary analysis for Cohort 1 and Cohort 2 will occur after 60 KTE-X19 subjects have been 
enrolled and treated in Cohort 1 and have had the opportunity to be evaluated for response 
6 months after the Week 4 disease assessment.  Data from both Cohort 1 and Cohort 2 will be 
analyzed.  However, as mentioned above, no statistical hypothesis will be formally tested on 
Cohort 1 axicabtagene ciloleucel subjects and Cohort 2 subjects, and, thus, no alpha-spending is 
assigned for the analysis of Cohort 1 axicabtagene ciloleucel subjects and Cohort 2 subjects.  The 
primary analysis on Cohort 1 will use a 1-sided alpha level of 0.025, with one interim efficacy 
analysis for futility.  This procedure preserves the designated overall alpha level (1-sided) of 
0.025 and achieves at least 96% power.
For Cohort 1, a rho (parameter = 0.30) beta spending function will be used to allocate the beta 
level between the futility analysis and the primary efficacy analysis.  The non-binding futility 
boundary for this interim analysis is reached if no more than 5 responders (≤5) out of 20 subjects 
are observed.  EAST version 6.4 was used to evaluate the statistical power and operating 
characteristics of this design. 
A follow-up analysis of subjects treated with KTE-X19 will be performed after all subjects in the 
mITT set of Cohort 1 have had the opportunity to be assessed for response 18 months after the 
first objective response. This additional analysis will be descriptive. The final analysis of Cohort 
1 and Cohort 2 will occur when all subjects in both cohorts have completed the study.
The primary analysis in Cohort 3 will be conducted after 86 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be assessed for response 6 
months after the first objective response or 9 months after the KTE-X19 infusion, whichever is 
earlier. In this analysis, inferential testing on efficacy in Cohort 3 will be performed using a 1-
sided alpha level of 0.025. This procedure preserves the designated overall alpha level (1-sided) 
of 0.025 and has at least 90% power when 86 subjects are included. EAST version 6.5 was used 
for power calculation and evaluation of the operating characteristics of this design.
A follow-up analysis will be performed after 86 subjects in Cohort 3 have had the opportunity to 
be assessed for response 18 months after the first objective response to further evaluate the risk-
benefit profile of KTE-X19, including the durability of response. This analysis will be 
descriptive.
Additional descriptive analyses may occur after the primary analysis and follow-up analyses 
described above have been completed. The final analysis of Cohort 3 will occur when all 
subjects in Cohort 3 have completed the study.


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3.4.
Statistical Assumptions
As described in Section 3.3, an open-label 3-cohort design is used for this study.  In the Cohort 1 
KTE-X19 subjects, a target ORR of 50% and a historical control rate of 25% are assumed for 
statistical inference.  In Cohort 3, a target response rate of 75% and a historical control rate of 
57% are assumed for statistical inference. The responses from subjects in the study population 
are assumed to be independent and follow binomial distribution, and, thus, an exact binomial test 
will be used to test the statistical hypothesis. 


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4.
STUDY ENDPOINTS AND COVARIATES
4.1.
Endpoints
4.1.1.
Primary
•
ORR, defined as the incidence of complete response (CR) or partial response (PR) per the 
Lugano Classification {Cheson 2014} as determined by the IRRC review
4.1.2.
Secondary
•
Duration of response (DOR)
•
Best objective response
•
ORR per investigator review
•
Progression-free survival (PFS)
•
Overall survival (OS) 
•
Incidence of adverse events (AEs) and clinically significant changes in laboratory values
•
Incidence of anti-CD19 CAR antibodies
•
Levels of anti-CD19 CAR+ T cells in blood
•
Levels of cytokines in serum
•
Changes over time in the European quality of life-5 dimensions (EQ-5D) scale score and 
EQ-5D visual analogue scale (VAS) score
•
Changes in the EORTC-QLQ-C30 score from baseline over time (Cohort 3 only)
4.1.3.
Exploratory
CCI


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4.2.
Covariates
4.2.1.
Baseline Covariates
The following baseline covariates may be used to examine efficacy and/or safety in subgroups or 
covariate analyses:
•
Eastern Cooperative Oncology Group (ECOG) performance status at baseline (0, 1, 2, 3, 4)
•
Age (in years) at baseline (< 65, ≥ 65)
•
Sex (male, female)
•
Race:  white, Asian, American Indian or Alaska Native, Black or African American, Native 
Hawaiian or Other Pacific Islander, other (categories may be collapsed or expanded based on 
accrual)
•
Relapsed/Refractory subgroup (relapsed after autologous stem cell transplant [auto-SCT], 
relapsed after last mantle cell lymphoma [MCL] chemotherapy, refractory to last MCL 
chemotherapy) 
•
Morphologic characteristics (blastoid, pleomorphic, diffuse, mantle zone, nodular)
•
Ki-67 index (%) (< 30%, ≥ 30%, < 50%, ≥ 50%)
•
t(11; 14) (Y/N)
•
Cyclin D1 overexpression (Y/N)
•
Disease stage (I, II, III, IV) and extent (presence of B symptoms, S [splenic involvement], 
E [extranodal disease], X [bulky disease], bone marrow involvement) as determined by the 
investigator at screening
•
Simplified Mantle Cell Lymphoma International Prognostic Index (s-MIPI)
•
Number of prior regimens
•
Prior Bruton tyrosine kinase inhibitors (ibrutinib vs acalabrutinib) for Cohort 1 and Cohort 2
CCI


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•
Prior therapy regimens (anti-CD20 [Y/N], anthracycline [Y/N], bendamustine [Y/N], 
ibrutinib [Y/N], acalabrutinib [Y/N], lenalidomide [Y/N], bortezomib [Y/N], temsirolimus 
[Y/N], stem cell transplant [Y/N], platinum [Y/N])
•
Tumor burden, as measured by the SPD of selected nodes or lesions at baseline
•
Lactate dehydrogenase (LDH), as weighted to upper limit of normal (< 0.67*ULN, >= 
0.67*ULN and < ULN, >= ULN and < 1.5*ULN, >=1.5*ULN)
4.2.2.
Tocilizumab and Steroid use after Anti-CD19 CAR T Cells Infusion
Post-baseline tocilizumab and steroid use may be used to examine efficacy in subgroups or 
covariate analyses:
•
Tocilizumab use after Anti-CD19 CAR T cells infusion (Y/N)
•
Steroids use after Anti-CD19 CAR T cells infusion (Y/N)
•
Tocilizumab or steroids use after Anti-CD19 CAR T cells (Y/N)
•
Tocilizumab and steroids use after Anti-CD19 CAR T cells (Y/N)
Covariate levels that are sparse may be collapsed for purposes of statistical modeling.


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5.
DEFINITIONS
5.1.
General
Study enrollment:  Study enrollment occurs when a subject commences leukapheresis. 
Study Day 0:  Day 0 is defined as the day the subject receives the first anti-CD19 CAR T cells 
infusion.  The day prior to Day 0 will be Day –1.   Any days after enrollment and prior to Day –1 
will be sequential and negative integer-valued. 
Baseline:  The baseline value is defined as the last value taken prior to conditioning 
chemotherapy.
Study therapy:  Study therapy includes conditioning chemotherapy and anti-CD19 CAR T cells.
On-study:  Time from enrollment to the last date of contact.
End of study:  Defined as when the last subject is assessed or received an intervention for 
evaluation in the study, including survival assessments.
Relapsed/Refractory subgroup:  Relapsed/refractory subgroups are defined as below.  Subjects 
meeting both “Relapsed after SCT” and any of the other categories will be categorized as 
“Relapsed after SCT.”  Note that bridging therapies should not be included for defining the 
Relapsed/Refractory subgroups.
•
Relapsed after SCT:  A subject is considered to be relapsed after SCT if the subject 
experienced relapse (nonresponse, disease recurrence or disease progression) after SCT.
•
Refractory to last MCL therapy:  A subject is considered to be refractory to the last MCL 
therapy if the subject failed to achieve a PR or CR to the last MCL therapy.
•
Relapsed after last MCL therapy:  A subject is considered to be relapsed after last MCL 
therapy if the subject responded and subsequently experienced disease progression after the 
last MCL chemotherapy.
Bulky disease:  Bulky disease is defined as the presence of a single lesion with largest diameter 
being 10 cm or larger or mediastinum wider than 1/3 of the chest on a chest x-ray.  The presence 
of bulky disease will be determined by the investigator when baseline disease extent is evaluated.
Actual follow-up time:  Actual follow-up time among all subjects treated with anti-CD19 CAR 
T cells is calculated as the time from the first dose of anti-CD19 CAR T cells to the date of 
death, last date known to be alive, lost to follow-up, or full withdrawal of consent, whichever is 
later.
Potential follow-up time:  Potential follow-up time is defined as the time from the anti-CD19 
CAR T cells infusion to the data cutoff date for the analysis.


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5.2.
Safety
Treatment-emergent adverse event (TEAE):  Any adverse event with onset on or after the 
anti-CD19 CAR T cells infusion.  All TEAEs will be summarized by preferred term and toxicity 
grade.  AEs occurred within other study periods may be summarized as appropriate.  For subjects 
taking retreatment of KTE-X19/axicabtagene ciloleucel, TEAEs during retreatment period may 
be summarized separately. 
Deaths:  All deaths that occur from the beginning of the chemotherapy conditioning period up 
through the end of study will be summarized.  Deaths that occur from the anti-CD19 CAR T 
cells infusion up through 30 days after the infusion will also be summarized.  For subjects taking 
retreatment of KTE-X19/axicabtagene ciloleucel, deaths occurred during retreatment period may 
also be summarized separately. 
AEs of special interest:  Adverse events of special interest for KTE-X19/axicabtagene ciloleucel 
treatment include identified risks (CRS, neurologic events, cytopenias, infections, and 
hypogammaglobulinemia) and potential risks (immunogenicity, secondary malignancies, RCR, 
and tumor lysis syndrome [TLS]).
CRS will be identified via collection of the syndrome on a case report form (CRF) specifically 
designed to record CRS.  Specific individual symptoms of CRS (eg, fever) collected on the AE 
log will be coded using Medical Dictionary for Regulatory Activities (MedDRA) and linked to 
the corresponding CRS episode.  Individual symptoms of CRS will be graded per Common 
Terminology Criteria for Adverse Events (CTCAE) v 4.03, and CRS as a syndrome will be 
graded per modified Lee criteria ((Lee et al, 2014).  In the modified grading scale, neurologic 
AEs are not to be reported as part of the CRS syndrome and will be reported separately and 
summarized separately. 
Neurologic events will be identified with a search strategy based on known neurologic toxicities 
associated with anti-CD19 immunotherapy ({Topp 2015}).  The search strategy focuses on 
central nervous system (CNS) toxicity, without regard to relatedness, temporal relationship, or 
concomitant conditions (eg, CRS). Additionally, the MedDRA system organ classes (SOCs) of 
Psychiatric Disorders and Nervous System Disorders will be reviewed for additional events; 
these events will then be evaluated for potential inclusion as neurologic AEs.
Immunogenicity will be identified by the development of antibodies to antibodies against CAR 
expressing cells by flow cytometry.  In addition, a manual review of the AE terms indicative of 
autoimmunity, inclusive of infusion-related events and anaphylactic reactions among subjects 
who test positive for anti-CD19 CAR antibodies, will be performed.
For other AEs of special interest, specific adverse events may be mapped to these categories 
using dictionary coded event term and standardized MedDRA queries (SMQs) or other search 
strategies.  Specific definitions of these events and the coded terms to which they correspond will 
be provided in the Program Safety Analysis Plan. 


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Duration of an AE of special interest: The duration of an AE of special interest may be derived 
only among subjects for whom all events of the class have resolved by the analysis data cutoff 
date.  The duration is defined as the stop day of the last AE in the event class – the start day of 
the first AE in the event class + 1.  
5.3.
Efficacy
ORR:  ORR is the proportion of subjects with either a CR or PR while on study.  All subjects 
who do not meet the criteria for objective response by the analysis data cutoff date will be 
considered non-responders, including the subjects with non-evaluable assessment data and those 
without any assessment. The derivation of this endpoint will only include response assessments 
obtained prior to any other additional therapy (eg, SCT or subsequent anti-cancer therapy or 
retreatment with anti-CD19 CAR T cells).  Response may be defined per Central Read or 
Investigator Read.
DOR:  DOR is defined only for subjects who experience an objective response and is the time 
from the first objective response to disease progression or death.  Response and progression may 
be defined per Central Read or Investigator Read.  Data from retreatment period will not be 
included for analysis. Subjects not meeting the criteria for progression or death by the analysis 
data cutoff date will be censored at their last evaluable disease assessment date.  DOR will be 
derived using disease assessments obtained on study prior to initiation of new anti-cancer 
therapy (including SCT).  The DOR for subjects who undergo SCT while in remission will be 
censored at the last evaluable disease assessment date prior to SCT; the DOR for subjects that 
undergo other new anti-cancer therapies including the retreatment with anti-CD19 CAR T cells 
in the absence of documented relapse will be censored at the last evaluable disease assessment 
prior to the new anti-cancer therapies.  A sensitivity analysis will be conducted in which disease 
assessments obtained after SCT are included in the derivation of DOR. Additional details on the 
derivation of DOR are provided in Appendix 3. In case that 5% or more subjects with two or 
more consecutive disease assessments missed prior to receiving SCT or new anti-cancer therapy, 
another sensitivity analysis will be performed with such subjects being counted as events and 
their DOR event time imputed based on the first missed scheduled assessment visit prior to the 
SCT or new anti-cancer therapy. 
PFS:  PFS is defined as the time from the anti-CD19 CAR T cells infusion date to the date of 
disease progression or death from any cause. For PFS analysis with the full analysis set (defined 
in Section 6.4) in which enrolled but not treated subjects are included, the PFS time will be 
calculated. as the time from the enrollment date to the date of disease progression or death from 
any cause. Progression may be defined per Central Read or Investigator Read.  Data from 
retreatment period will not be included for analysis.  Subjects alive and not meeting the criteria 
for progression by the analysis data cutoff date will be censored at their last evaluable disease 
assessment date.  PFS will be derived using disease assessments obtained on study prior to 
initiation of new anti-cancer therapy (including SCT).  The PFS for subjects who undergo SCT 
while in remission will be censored at the last evaluable disease assessment date prior to SCT; 
the PFS for subjects that undergo other new anti-cancer therapies in the absence of documented 
relapse will be censored at the last evaluable disease assessment prior to the new anti-cancer 


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therapies. A sensitivity analysis will be conducted in which disease assessments obtained after 
SCT are included in the derivation of PFS.  Additional details on the derivation of PFS are 
provided in Appendix 3. 
OS:  OS is defined as the time from the anti-CD19 CAR T cells infusion to the date of death 
from any cause.  Subjects who have not died by the analysis data cutoff date will be censored at 
the last date known to be alive or the data cutoff date, whichever is earlier. For OS analysis with 
the full analysis set, the OS time will be calculated as the time from the enrollment date to the 
date of death from any cause. Additional details on the derivation of overall survival and the 
specific data modules that will be used to derive the last date known to be alive are provided in 
Appendix 3.  
Duration of response to retreatment (DORR):  DORR is defined the same as DOR, except 
that the definition applies to the response after KTE-X19/axicabtagene ciloleucel retreatment.


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6.
ANALYSIS SETS
Analysis sets are defined within each cohort as follows.
6.1.
Modified Intent-to-treat
The mITT analysis set will consist of all subjects enrolled and treated with any dose of 
anti-CD19 CAR T cells.  This analysis set will be used for efficacy analyses for Cohort 1 
subjects treated with axicabtagene ciloleucel, Cohort 2 subjects, and Cohort 3 subjects. For 
Cohort 3, this analysis set will be used for the hypothesis testing of the primary endpoint ORR.
6.2.
Inferential Analysis Set
The inferential analysis set will consist of the first 60 treated KTE-X19 subjects in Cohort 1. 
This analysis set will be used for efficacy analyses in Cohort 1 and also the hypothesis testing of 
the primary endpoint ORR for Cohort 1 at the time of the primary analysis.
6.3.
Safety Analysis Set
The safety analysis set is defined as all subjects treated with any dose of anti-CD19 CAR T cells 
(same as mITT).
6.4.
Full Analysis Set
The full analysis set (FAS) will consist of all enrolled subjects and will be used for the summary 
of subject disposition. This analysis set will also be used for analyses of objective response rate 
and other key efficacy endpoints (BOR, DOR, PFS, and OS).
6.5.
mITT Retreatment Analysis Set
The mITT retreatment analysis set will consist of all subjects who undergo retreatment with any 
dose of anti-CD19 CAR T cells.  This set will be used for all retreatment efficacy analyses.
6.6.
Safety Retreatment Analysis Set
The safety retreatment analysis set will consist of all subjects who undergo retreatment with 
anti-CD19 CAR T cells.
Note that subjects treated with anti-CD19 CAR T cells to expanded access (ie, “compassionate 
use” subjects not treated under Protocol KTE-C19-102) will not be included in the safety 
analysis set or the mITT analysis set. 
6.7.
Subgroup Analysis Sets
Subgroup analyses of selected efficacy and safety endpoints may be performed for subgroups 
defined by the baseline covariates defined in Section 4.2.  


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7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES
7.1.
Interim Analysis
In Cohort 1 and Cohort 2, an independent DSMB will be chartered to make recommendations on 
study conduct.  The DSMB will meet 4 times during the study (Cohort 1 interim analysis 1, 
Cohort 1 interim analysis 2, Cohort 1 interim analysis 4, and Cohort 2 interim analysis 1), as 
described in Section 3.1 and Section 3.3.  The DSMB will review safety and efficacy data and 
will be chartered to make trial conduct recommendations based on the risk versus benefit of 
treatment with anti-CD19 CAR T cells.  For Cohort 1, a rho (parameter = 0.30) beta spending 
function will be used to allocate the beta level between the futility analysis at Cohort 1 interim 
analysis 2 and the primary efficacy analysis.  The non-binding futility boundary for this interim 
analysis is reached if no more than 5 responders (≤ 5) out of 20 subjects are observed.   
Details of the DSMB composition and responsibilities may be found in the DSMB charter.  
In addition to the 4 interim analyses for Cohort 1 and Cohort 2 to be reviewed by DSMB, an 
additional interim analysis (Cohort 1 interim analysis 3) will be performed for a Kite internal 
review of the accumulating data of safety and efficacy (see Section 3.3).  After the planned 
primary analysis of the study, additional efficacy and safety analyses may be performed to 
support regulatory interaction or publications.  These analyses will be descriptive.
In Cohort 3, a SSC, comprising the study sponsor and at least 3 study investigators, will be 
specifically chartered to review the safety data from Cohort 3 and make recommendations on 
further study conduct. 
The SSC will meet after 15 subjects in Cohort 3 have been enrolled and treated with KTE-X19 
and have had the opportunity to be followed for 30 days, and again after 50 subjects in Cohort 3 
have been enrolled and treated with KTE-X19 and have had the opportunity to be followed for 3 
months. The SSC may meet more often as needed.  
No interim analyses for efficacy will be performed in Cohort 3. 
The DSMB and SSC will also monitor safety criteria to pause enrollment in the respective 
cohorts.
7.2.
Assessment of Criteria to Pause Enrollment
As part of its oversight of the study, the DSMB for Cohort 1 and Cohort 2, will also assess 
criteria to pause enrollment after 10, 20, 30, and 50 subjects treated with anti-CD19 CAR T cells 
in Cohort 1 have had the opportunity to be followed for 30 days.  


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The assessments of criteria to pause enrollment will be triggered when 10, 20, 30, and 
50 subjects have been treated with anti-CD19 CAR T cells and have had the opportunity to be 
followed for 30 days.  At each assessment, the subject incidence of the events listed in the below 
criteria will be tabulated for the first treated 10 subjects, 20 subjects, 30 subjects, and 
50 subjects, respectively.  If either criterion is met (with incidence rates calculated with 
10 subjects, 20 subjects, 30 subjects, and 50 subjects as denominators, respectively) prior to an 
assessment milestone, the DSMB will proceed with the assessment with available data. 
For Cohort 3,  a SSC will meet after 15 subjects in Cohort 3 have been enrolled and treated with 
KTE-X19 and have had the opportunity to be followed for 30 days, and again after 50 subjects in 
Cohort 3 have been enrolled and treated with KTE-X19 and have had the opportunity to be 
followed for 3 months. The SSC may review data more often as needed. 
As part of its oversight of the study, the SSC will also assess criteria to pause enrollment in 
Cohort 3 after 15 subjects in Cohort 3 have been enrolled and treated with KTE-X19 and have 
had the opportunity to be followed for 30 days, and again after 50 subjects in Cohort 3 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed for 3 months, 
using the criteria described below. The SSC may request additional analyses of safety data if a 
safety concern arises during the course of the trial. 
Enrollment will be paused if any of the following criteria is met:
•
Incidence of Grade 5 KTE-X19/axicabtagene ciloleucel-related adverse events within 
30 days is > 10%.
•
Incidence of the following Grade 4 KTE-X19/axicabtagene ciloleucel-related adverse events 
lasting more than 7 days is > 33%:
Neurologic toxicities
CRS (per Lee 2014 criteria)
Other non-hematological serious adverse event (SAE)
Infection (treatment-related)
The DSMB and SSC will monitor safety criteria to pause enrollment in the respective cohorts.
7.3.
Access to Aggregate and Subject-level Data and Individual Subject 
Treatment Assignments
This study is open label.  Subjects, the study sponsor, and investigators will be aware that each 
subject is planned to be treated with KTE-X19/axicabtagene ciloleucel.  Data handling 


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procedures designed to maintain the trial credibility and validity in this study are described in the 
Trial Integrity Document.
For Cohort 1 and Cohort 2, an independent statistician will perform Cohort 1 interim analysis 1, 
Cohort 1 interim analysis 2, Cohort 1 interim analysis 4, and Cohort 2 interim analysis for the 
study, as well as the safety assessment to pause enrollment, and provide these reports to the 
DSMB.  Members of the DSMB and independent statistician will not have any direct contact 
with study center personnel or subjects.  The DSMB will communicate recommendations to Kite 
Pharma in accordance with the DSMB charter. Additional details of the DMSB composition and 
reviews are described in the DSMB charter.
For Cohort 3, the sponsor will perform Cohort 3 interim analyses for SSC review. More details 
can be found in the SSC charter.


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8.
DATA SCREENING AND ACCEPTANCE
8.1.
General Principles
The database will be subject to the edit checks outlined in the Data Management Plan and 
additional manual data reviews defined by the study team.  Data inconsistencies will be reviewed 
and resolved before the database snapshot for the primary analysis and the final database lock.  
For interim analyses, snapshots may include data that has not passed all data cleaning procedures 
at the time the data are extracted for snapshot.  
8.2.
Electronic Transfer and Archival of Data
The Medidata Rave system will be used to collect the data in this study.  Raw data extracted 
from Medidata Rave will be archived prior to further dataset creation, maintenance, and analysis.  
Datasets (raw data, study data tabulation model [SDTM] data, and/or analysis data model 
[ADaM] data) for planned analyses will be archived.  Any additional unplanned analyses that 
occur after the primary analysis and prior to the final analysis will also be archived.  Key data 
external to the clinical study database (see below) will be included in the relevant SDTM and 
ADaM modules when the external data are available.
Data from the central pathology laboratory (including tumor pathology, tumor genetic, and 
molecular characteristics), the product manufacture (total T cells, CAR T cells [transduction 
ratio], duration of manufacturing time), central laboratory assessment of subject serum samples 
(including CAR T cell levels in the peripheral blood, antibody assays, RCR testing), and central 
radiology review will be generated from contract laboratories and Kite Pharma.  These data will 
be transferred to Kite and held in a peripheral directory and not built into the clinical trial 
database.  At the time when analyses require these data, they may be merged with the SDTM and 
ADaM datasets.
8.3.
Handling of Missing and Incomplete Data
8.3.1.
Efficacy
The method for handling missing data is described in the definition for each efficacy endpoint.  
Every effort will be made to obtain complete dates for deaths.  In the event of a partial or missing 
death date and the corresponding censoring date for survival, the algorithm in Appendix 1 will be 
used.
8.3.2.
Safety
Partial AE start dates will be imputed.  If dates are missing or incomplete for adverse event start 
dates, the algorithm defined in Appendix 1 will be used.  Completely missing death dates or 
death dates with only a year reported will not be imputed.


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8.4.
Detection of Bias
A listing of subjects with important protocol deviations will be generated.  The deviations 
included in this list will include, but not be limited to, violations of eligibility criteria and use of 
exclusionary medication during the study.  Lack of protocol compliance will be evaluated by 
summarizing the subject incidence of important protocol deviations.  High rates of important 
protocol deviations may indicate bias.
Endpoints derived from investigator assessment of radiologic scans and disease assessments may 
be subject to bias; the concordance between investigator and central review of radiologic scans 
and disease assessments will be summarized where appropriate.
8.5.
Outliers
Descriptive statistics may be used to identify potential outliers in any key variables analyzed.  
Suspected outliers will be included in all analyses unless there is sufficient scientific justification 
to exclude them.
8.6.
Distributional Characteristics
The primary analysis of the primary endpoint is an exact binomial test used to compare the 
observed ORR per Central Read to a response rate of 25% in the Cohort 1 inferential analysis set 
and 57% in the Cohort 3 mITT analysis set. These tests assume the independence of the 
individual subject responses.  
An exact 95% confidence interval will be generated about the ORR.  The Clopper-Pearson 
method will be used to generate this interval.  
8.7.
Validation and Configuration Management
Programs for the development of the SDTM and ADaM datasets and the generation of the tables, 
figures, and listings will be developed and maintained according to Cytel Inc. Standard 
Operating Procedures (SOPs) and Kite SOPs if applicable.  The software and version used to 
generate analyses will be indicated in the archived documentation.


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9.
STATISTICAL METHODS OF ANALYSIS
9.1.
General Principles
The goal of the primary statistical analysis is to compare the observed ORR per Central Read to 
a historical control rate of 25% in the Cohort 1 inferential analysis set and 57% in Cohort 3 
mITT analysis set, respectively. Hypothesis testing will be one-sided, and all 95% confidence 
intervals will be 2-sided.  At the time of the primary analysis, 95% confidence intervals for ORR 
will be presented for Cohort 1 inferential analysis set subjects and Cohort 3 mITT analysis set 
subjects. ORR with 95% confidence intervals may be generated for Cohort 1 axicabtagene 
ciloleucel subjects, and Cohort 2 subjects, respectively, for descriptive purpose only.
The timing of the interim and primary analyses will be based on subject accrual and safety or 
disease assessment milestones.  The primary analysis Clinical Study Report will be written at the 
primary analysis of the study.  The Clinical Study Report may be amended with additional 
subject safety and survival follow-up after the planned primary analysis.
9.2.
Subject Accountability
The number of subjects screened, enrolled/leukapheresed, treated with bridging therapy, treated 
with conditioning chemotherapy, treated with anti-CD19 CAR T cells, and retreated with 
anti-CD19 CAR T cells will be summarized.  The reasons for discontinuing treatment and 
discontinuing study will be summarized.
Summaries of actual and potential follow-up time among all subjects treated with anti-CD19 
CAR T cells will be provided.
The number of subjects enrolled by country and site will be summarized.  
The number of subjects in each analysis set will be provided.
9.3.
Important Protocol Deviations
The clinical study team will define important protocol deviation categories and review all 
potential important protocol deviations at minimum, prior to the database snapshot for the 
primary efficacy analysis.  Important protocol deviations will be categorized by deviation type 
(eg, entry eligibility, use of excluded medication).  The subject incidence of important protocol 
deviations will be summarized overall and by deviation category.
9.4.
Demographic and Baseline Characteristics
Summary statistics and frequencies for the demographic and baseline characteristics as listed in 
Section 4.2.1 will be tabulated.


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9.5.
Efficacy Analyses
The hypothesis testing of ORR will be conducted on the inferential analysis set in Cohort 1 and 
mITT analysis set in Cohort 3, respectively. Other efficacy analyses will also be conducted on 
the inferential analysis set for Cohort 1 KTE-X19 subjects. Efficacy analyses for Cohort 1 
axicabtagene ciloleucel subjects, Cohort 2 subjects and Cohort 3 subjects will be conducted on 
the mITT analysis set. FAS will also be used for analyses on key efficacy endpoints (ORR, BOR, 
DOR, PFS, and OS). For the primary analysis, the IRRC assessments based on the Lugano 
Classification {Cheson 2014}, referred to as “Central Read,” will be used.  Sensitivity analyses 
will be conducted based on the investigator assessments.  For Cohort 1, the Investigator Read 
will be based on the revised International Working Group Criteria for Malignant Lymphoma 
{Cheson 2007}; for Cohort 2 and Cohort 3, the investigator review will be based on the Lugano 
Classification {Cheson 2014}.  The independent radiology reviewers and investigators will 
provide the determination of disease status (CR, PR, SD, PD, not evaluable [NE]) at each time 
point.  Statistical analysis system (SAS) programs will be used to derive the best overall 
response, DOR, and PFS based on these assessments.  Efficacy analyses of Cohort 1 
axicabtagene ciloleucel subjects and Cohort 2 KTE-X19 subjects will be descriptive.
The analysis of objective response rate and DOR will be presented in the following analysis sets:
•
Inferential analysis set (Cohort 1 KTE-X19 subjects)
•
mITT analysis set 
•
FAS 
Disease assessment obtained after retreatment will not be used in the primary summaries of 
objective and best response, DOR, and PFS.  For such subjects, disease assessments obtained 
after retreatment will be included in the summaries of objective and best response to retreatment 
with anti-CD19 CAR T cells and DORR.  The subject’s OS time will be derived from the last 
date known to be alive regardless of retreatment time.
In the event any subject undergoes an autologous or allogeneic SCT or any other anti-cancer 
therapy while on study, the subject’s best response will be derived only based on disease 
outcomes assessed prior to SCT or initiation of new therapy, whichever is earlier.  For subjects 
without documentation of progression prior to initiation of new therapy (including SCT), DOR 
and PFS time will be censored at the last disease assessment prior to the initiation of new therapy 
(including SCT).  A sensitivity analysis for DOR will be conducted in which disease assessments 
after SCT are included to derive events and censoring times for subjects who undergo SCT while 
in KTE-X19/axicabtagene ciloleucel-induced response.  (See details in Appendix 3.)  


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9.5.1.
ORR and Best Response
9.5.1.1.
Primary Analyses of ORR per Central Read
The subject incidence of objective response per Central Read will be calculated.  The subject 
incidence of best response (CR, PR, SD, PD, NE) per Central Read will be tabulated.  
Confidence intervals will be provided about the ORR and best response, calculated with the 
following methods:
•
Clopper-Pearson (an exact interval)
An exact binomial test will be used to compare the observed ORR per Central Read to the 
hypothesized historical control rate specified previously. 
The analysis of ORR and best response per Central Read will include subjects from the 
Inferential analysis set for Cohort 1 and mITT analysis set for Cohort 2 and Cohort 3.  Analysis 
of objective response in Cohort 1 KTE-X19 subjects and Cohort 3 subjects will also be 
conducted using the FAS.
9.5.1.2.
Analyses of Objective Response and Best Response per Investigator Read
The analyses of ORR and best response specified above will be repeated for ORR and best 
response per Investigator Read.
The concordance of objective response and best response per Central Read and Investigator Read 
will be evaluated in Cohort 1.  A summary table of concordance, concordance rate, a kappa 
statistic, and a 2-sided 95% confidence interval about the kappa statistic will be provided.
Further analyses comparing the Investigator and Central Reads may be performed as appropriate. 
9.5.1.3.
Subgroup Analyses of ORR
ORR and 95% confidence intervals will be generated for subgroups defined by each of the 
categorical covariates in Section 4.2.1 of the inferential analysis set of Cohort 1 KTE-X19 
subjects and mITT set of Cohort 3 subjects. Subgroup analysis with additional covariates may 
also be explored.
A forest plot of the proportion of responders for each of these subgroups will be generated.  
9.5.2.
DOR  
The Kaplan-Meier approach will be used to estimate DOR.  The number of subjects censored 
and the reasons for censoring will be summarized.  Analyses will be generated for DOR per 
Central Read, as well as per Investigator Read.  The reverse Kaplan-Meier approach {Schemper 
1996} will be used to estimate the follow-up time for DOR.    
A sensitivity analysis of DOR will be conducted in which disease assessments obtained after 
SCT (for subjects who undergo SCT while in a KTE-X19/axicabtagene ciloleucel induced 


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response) are used in the derivation of DOR. In case that 5% or more subjects with two or more 
consecutive disease assessments missed prior to receiving SCT or new anti-cancer therapy, 
another sensitivity analysis will be performed with such subjects being counted as events and 
their DOR event time imputed based on the first missed scheduled assessment visit prior to the 
SCT or new anti-cancer therapy. 
An analysis of DOR will also be conducted in the FAS for Cohort 1 KTE-X19 subjects and 
Cohort 3 subjects.  
DOR may be summarized in subgroups defined by the best response attained on study.
9.5.3.
PFS
Kaplan-Meier plots, estimates, and 2-sided 95% confidence intervals will be generated for PFS.  
Estimates of the proportion of subjects alive and progression-free at 3-month intervals will be 
provided.  The number of subjects censored and the reasons for censoring will be summarized.  
Analyses will be generated for PFS per Central Read and PFS per Investigator Read.
A sensitivity analysis will be conducted in which disease assessments obtained after SCT (for 
subjects undergoing SCT while in a KTE-X19/axicabtagene ciloleucel induced response) are 
included in the derivation of PFS. 
A PFS analysis will also be conducted in the FAS.
Subgroup analyses of the PFS rate at 6 months may be generated in subgroups defined by the 
covariates in Section 4.2.
PFS may be summarized in subgroups defined by the best response attained on study.
9.5.4.
OS
The analysis of OS will use the same methods as the analysis of PFS. An OS analysis will also 
be conducted in the FAS.
OS may be summarized in subgroups defined by the best response attained on study.
9.5.5.
Tumor Burden
The change in tumor burden, as measured by the SPD of the selected lesions (reported as target 
lesions), from baseline to post-baseline nadir will be summarized in absolute numbers (mm2) and 
percentage.  A graphical summary of this change will be presented in a vertical bar chart with 
each subject’s percent change from baseline to nadir displayed as a vertical bar, with color 
coding that indicates best response attained (“waterfall” plot). Analyses will be generated for 
change in tumor burden per Central Read and per Investigator Read. Data collected after new 
anti-cancer therapy, retreatment of anti-CD19 CAR T cells, or SCT will not be included for the 
analyses.


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9.5.6.
Objective Response and Best Response Among Subjects Retreated with Anti-
CD19 CAR T Cells
The incidence of subjects retreated with anti-CD19 CAR T cells will be tabulated or listed.  ORR 
and best response (CR, PR, SD, PD, NE) to the retreatment among subjects retreated with 
anti-CD19 CAR T cells will be calculated.  Confidence intervals may be provided about the 
ORR and best response to the retreatment.  Analyses may be conducted per Central Read and 
Investigator Read.
9.5.7.
DORR
The analysis of DORR may be conducted using the same methods as the analysis of DOR and 
performed using the mITT retreatment analysis set..
9.5.8.
Incidence of SCT
The subject incidence of SCT post-treatment with anti-CD19 CAR T cells and prior to disease 
progression will be tabulated among subjects who undergo SCT while in KTE-X19/axicabtagene 
ciloleucel induced response. 
9.5.9.
European Quality of Life-5 Dimensions and Visual Analogue Scale Scores
EQ-5D and VAS scores will be summarized at baseline and post study treatment visits.  Changes 
in the EQ-5D-5L and VAS scores from baseline at each post-study treatment visit will also be 
summarized with descriptive statistics.
9.5.10.
European Organization for Research and Treatment of Cancer Quality of 
Life Questionnaire (EORTC-QLQ-C30) scores
For Cohort 3, EORTC-QLQ-C30 scores will be summarized at baseline and post study treatment 
visits.  Changes in the EORTC-QLQ-C30 scores from baseline at each post-study treatment visit 
will also be summarized with descriptive statistics.
9.6.
Safety Analyses
Safety analyses will be conducted on the safety analysis set for Cohort 1 KTE-X19 subjects, 
Cohort 1 axicabtagene ciloleucel subjects, Cohort 2 subjects, and Cohort 3 subjects, separately. 
Safety analysis will also be conducted on the treated KTE-X19 subjects combined from Cohort 1 
and Cohort 2. The primary analysis of safety data will summarize TEAEs, death, and laboratory 
values with onset on or after the anti-CD19 CAR T cells infusion date and prior to retreatment 
period (if applicable).  Additional summary tables may be provided to present the AEs that 
occurred within certain study periods.  For subjects who undergo retreatment with anti-CD19 
CAR T cells, AEs occurring in the retreatment period may be summarized or listed separately.  
Sample table layouts are provided in Appendix 2.


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AEs will be coded with the MedDRA at the time of each analysis.  The version of the MedDRA 
may vary over time as the current version in use is updated.  The severity of AEs will be graded 
using the National Cancer Institute CTCAE version 4.03.  
CRS will be graded using a revised CRS grading scale developed by Lee et al {Lee 2014}.  The 
incidence and severity of CRS will be reported as a syndrome with severity per Lee et al {Lee 
2014}.  Individual symptoms associated with CRS will be graded per CTCAE version 4.03. The 
severity of neurologic events in Cohort 3 will be graded using CTCAE version 4.03 and the 
American Society for Transplantation and Cellular Therapy (ASTCT) immune effector cell-
associated neurotoxicity syndrome (ICANS) consensus grading system. In Cohort 3, CRS will 
also be assessed by ASTCT grading {Lee 2019}. ASTCT grading is collected only for the 
purposes of comparison and will not be used for toxicity management. Fatal AEs that are 
attributed to disease progression may be included in the death summary with a primary death 
reason of “disease progression” regardless of the coded CTCAE version 4.03 preferred term.
Subjects enrolled, but not dosed with anti-CD19 CAR T cells, will be followed for AEs for 
30 days after the last study-specific procedure.  AEs reported in these subjects will be archived in 
the study database and available in SDTM and ADaM datasets, but will not be tabulated in AE 
summaries.
9.6.1.
AEs
The subject incidence of the following TEAEs will be tabulated:
•
Summary of AEs (any, worst severity, serious, treatment-related)
•
All AEs
•
All SAEs
•
All KTE-X19/axicabtagene ciloleucel-related AEs
•
All KTE-X19/axicabtagene ciloleucel-related SAEs
•
All Grade 3 or higher AEs
•
All Grade 3 or higher KTE-X19/axicabtagene ciloleucel-related AEs
•
Fatal AEs
•
AEs of special interest, including identified risks and potential risks 
The subject incidence of deaths by time periods will be provided.   
A subject listing of deaths through 30 days after anti-CD19 CAR T cells infusion will be 
provided overall and by treatment period.


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Subgroup analyses of AEs may be generated for selected covariates from the list in Section 4.2.1.  
The time to onset and resolution and the duration of CRS will be summarized. Cardiac 
arrhythmias and cardiac failure in the context of CRS may be summarized. 
The time to onset and resolution and the duration of neurologic events will be summarized. 
Especially neurologic events will be identified using two methods. One is defined by Topp and 
colleagues {Topp 2015} and the other one is defined by Kite.
Cytopenias will be summarized by categories of neutropenia, anemia, and thrombocytopenia; 
cytopenias present after 30 days from anti-CD19 CAR T cells infusion will also be summarized.
Infections will be summarized by categories (bacterial infections, viral infections, opportunistic 
infections, and other infections).
9.6.2.
Procedures and Concomitant Medications
The incidences of procedure and concomitant medications used to manage AEs will be tabulated 
(see Section 9.6.7).
9.6.3.
Laboratory Test Results
Laboratory results will be graded according to National Cancer Institute CTCAE version 4.03.  
The incidence of post-infusion worst-grade lab toxicities for all analytes will be summarized.  
Additional summaries for the shift from baseline to the worst toxicity grade after anti-CD19 
CAR T cells infusion may also be generated.
9.6.4.
Anti-CD19 CAR Antibodies
The subject incidence of any anti-CD19 CAR antibodies will be tabulated.  For subjects testing 
positive for antibodies, the persistence of the antibody over time will be listed and summarized 
9.6.5.
RCR
The subject incidence of RCR detected in blood samples will be tabulated overall and by 
assessment time.  The persistence of RCR over time will be summarized.
9.6.6.
Exposure to Study Treatment  
Summary statistics and subject listings will be provided for the following:
•
Total body surface area-adjusted dose of cyclophosphamide
•
Total body surface area-adjusted dose of fludarabine
•
Weight-adjusted dose of KTE-X19/axicabtagene ciloleucel


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•
Total CAR T cells of the KTE-X19/axicabtagene ciloleucel infusion
•
Total T cells of the KTE-X19/axicabtagene ciloleucel infusion
•
Transduction ratio
•
Percentages of CD4 and CD8 T cells
•
Percentages of T cell memory phenotypes
•
Interferon (IFN)-gamma production in co-cultures of KTE-X19/axicabtagene ciloleucel 
product and CD19+ target cells
•
Vector copy number of KTE-X19/axicabtagene ciloleucel product
Summaries may also be provided by demographics and baseline characteristics as appropriate.  
Separate summaries will be presented for the retreatment conditioning chemotherapy and 
KTE-X19/axicabtagene ciloleucel for subjects in the retreatment analysis set.
9.6.7.
Exposure to Concomitant Medications and Procedures
The subject incidence of concomitant medications will be summarized by medication category 
and WHO Drug coded term.   The subject incidence of procedures will be tabulated. The 
duration and indication of concomitant medications of interest, steroids and tocilizumab for 
example, may be summarized. 
9.6.8.
Mini-mental Status Exam or Immune Effector Cell-associated 
Encephalopathy
Summary statistics for the Mini-Mental Status Exam score and change from baseline in the 
Mini-Mental Status Exam score over time will be provided for all subjects in the safety analysis 
set in Cohort 1 and Cohort 2, and may be summarized within groups defined by the occurrence 
of Grade 3 or higher neurotoxicity.  
Summary statistics for the immune effector cell-associated encephalopathy score and change 
from baseline in the immune effector cell-associated encephalopathy score over time will be 
provided for all subjects in the safety analysis set in Cohort 3. 
9.7.
Subsequent Anti-cancer Therapy
The incidence of subsequent anti-cancer therapy (by WHO Drug coded term) will be 
summarized.
9.8.
Schedule of Study Treatment
Summary statistics will be provided for the following durations:
•
Days from leukapheresis to KTE-X19 product release 


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•
Days from leukapheresis to receipt of anti-CD19 CAR T cells at the study site 
•
Days from leukapheresis to administration of anti-CD19 CAR T cells
•
Duration of hospitalization for the anti-CD19 CAR T cells infusion
9.9.
CAR T Cells Measured in Peripheral Blood
Summary statistics for the level of CAR T cells in serum post KTE-X19/axicabtagene ciloleucel 
infusion will be provided for CAR T cells measured at Day 7, Week 2, Week 4, Month 3, 
Month 6, Month 12, and Month 24.  The maximum CAR T cell level attained, the time at which 
the maximum level was attained, and the time at which there were no detectable CAR T cells in 
the serum will be summarized.  The area under the concentration over time curve may be 
summarized from Day 0 to Day 28.
9.10.
B-cell Aplasia
The subject incidence of B-cell aplasia based on B cells measured by flow cytometry and the 
subject incidence of recovery of B-cells aplasia will be summarized. The use of intravenous 
immunoglobulin may be summarized.


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10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES
None.


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11.
REFERENCES
Brown LD, Cai TT, DasGupta A. Interval Estimation for a Binomial Proportion. Statistical 
Science 2001;16 (2):101-33.
Brown LD, Cai TT, DasGupta A. Confidence Intervals for a Binomial Proportion and 
Asymptotic Expansions. The Annals of Statistics 2002;30 (1):160-201.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. 
Recommendations for initial evaluation, staging, and response assessment of 
Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 
2014;32 (27):3059-68.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised 
response criteria for malignant lymphoma. J Clin Oncol 2007;25 (5):579-86.
Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, et al. A 
new prognostic index (MIPI) for patients with advanced-stage mantle cell 
lymphoma. Blood 2008;111 (2):558-65.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the 
diagnosis and management of cytokine release syndrome. Blood 2014;124 
(2):188-95. 
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT 
Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity 
Associated withImmune Effector Cells. Biol Blood Marrow Transplant 
2019;25:625-38
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin 
Trials 1996;17 (4):343-6.
Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity 
of blinatumomab for adult patients with relapsed or refractory B-precursor acute 
lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet 
Oncology 2015;16 (1):57-66.


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12.
HISTORY OF REVISIONS 
Version
Date
Protocol
Description of Changes
Original 
(1.0)
15JUN2017
Original to 
Amendment 3
N/A
2.0
17NOV2017
Amendment 4
•
Added Cohort 2 as pivotal cohort (N=40) and changed 
Cohort 1 to non-pivotal cohort and decreased Cohort 1 
sample size from N=67 to N=40;
•
Modified the interim and primary analyses accordingly;
•
Changed the primary efficacy endpoint from objective 
response rate (ORR) based on investigator read per 
Cheson 2007 to ORR based on Central Read per Lugano 
Classification (Cheson 2014);
•
Changed the hypothesis testing on ORR from 40% vs. 
20% to 50% vs. 25%; 
•
Added QoL (EQ-5D and VAS score) and RCR incidence 
rate as secondary endpoints;
•
Added prior acalabrutinib to baseline characteristics 
summary;
•
Other minor or cosmetic changes.
3.0
23APR2018
Amendment 4
•
Removed B-cell aplasia analysis; 
•
Simplified the section of definitions; 
•
Updated the potential risks and the analysis method;
•
Added language for QoL (EQ-5D and VAS score) 
summary;
•
Other minor or cosmetic changes.
4.0
12JUL2018
Amendment 5
•
Specified that Cohort 1 KTE-X19 subjects will form the 
basis for statistical hypothesis testing on the primary 
endpoint;
•
Increased the sample size of Cohort 1 from N=40 to 
N=~90 (with at least 60 XLP subjects); 
•
Specified that no hypothesis will be tested in the Cohort 
1 axicabtagene ciloleucel subjects or Cohort 2 subjects;
•
Added an interim analysis to Cohort 1; 
•
Changed the primary analysis time based on Cohort 1 
enrollment (ie, after 60 C1 KTE-X19 subjects have had 
the opportunity to be evaluated for response 6 months 
after week 4 disease assessment); 
•
Removed competing-risk analysis on DOR;
•
Other minor or cosmetic changes.


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Version
Date
Protocol
Description of Changes
5.0
22OCT2018
Amendment 6
•
Changed investigational product name from KTE-C19 to 
KTE-X19; 
•
Added a sensitivity analysis on DOR in the event of 5% 
or more subjects with two or more consecutive disease 
assessments missed prior to receiving SCT or new 
anti-cancer therapy;
•
Indicated that inferential analysis set will be used for all 
key efficacy analyses; 
•
Indicated that full analysis set will be used for efficacy 
analysis on ORR and other key efficacy endpoints;
•
Other minor or cosmetic changes.
6.0
8JUL2019
Amendment 6
•
Specified that inferential analysis set and FAS will be 
used for efficacy analyses in Cohort 1 KTE-X19 subjects 
while mITT set will be used for Cohort 1 axicabtagene 
ciloleucel and Cohort 2 efficacy analysis;
•
Added the PFS and OS definitions for FAS;
•
Indicated that safety analysis will also be done with all 
treated KTE-X19 subjects combined from Cohort 1 and 
Cohort 2;
•
Added back B-cell aplasia analysis;
•
Added summary for history of revisions; 
•
Other minor or cosmetic changes.


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Version
Date
Protocol
Description of Changes
7.0
09FEB2022
Amendment 7 to 
Amendment 8
•
Addition of Cohort 3 (~90 subjects) with BTKi-naïve 
subjects 
•
Hypothesis that the ORR to KTE-X19 per independent 
review is significantly greater than 57% in Cohort 3 
subjects 
•
Scientific steering committee (SSC) will review safety 
data for Cohort 3 to make recommendations on further 
study conduct 
•
Safety interim analysis will be conducted after 15 
subjects in Cohort 3 have been enrolled and treated with 
KTE-X19 and have had the opportunity to be followed 
for 30 days after infusion 
•
Cohort 3 interim analysis 2 will be conducted after 50 
subjects in Cohort 3 have been enrolled and treated with 
KTE-X19 and have had the opportunity to be followed 
for 3 months after the KTE-X19 infusion 
•
The primary analysis in Cohort 3 will occur after 86 
subjects in Cohort 3 have been enrolled and treated with 
KTE-X19 and have had the opportunity to be assessed 
for response 6 months after the first objective response 
or 9 months after the KTE-X19 infusion, whichever is 
earlier
•
Updated the section 3.1 of Study Design based on 
protocol amendment 8.
•
Added Cohort 3 in section 9.5 of the efficacy analysis.
•
Added ICANS in section 9.6 for Cohort 3 subjects.
•
Added immune effector cell-associated encephalopathy 
score analysis in section 9.6.8 for Cohort 3 subjects.


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13.
APPENDICES
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or 
Missing Dates
The following data will be imputed using the following algorithm:
•
Adverse event (AE) start dates
•
Deaths (see exceptions below)
•
Concomitant medication start dates
•
Subsequent anti-cancer therapy start dates
Table 1.
Imputation Rules for Partial or Missing Start Dates
Stop Date
Complete:  yyyymmdd
Partial:  yyyymm
Partial:  yyyy
Start Date
< Day 0
≥ Day 0
< Day 0 
yyyymm
≥ Day 0
yyyymm
< Day 0 
yyyy
≥ Day 0
yyyy
Missing
= Day 0
yyyymm
1
1
n/a
1
1
Partial
yyyymm
≠ day 0
yyyymm
2
2
2
2
2
2
2
= Day 0
yyyy
1
1
n/a
1
1
Partial
yyyy
≠ Day 0
yyyy
3
3
3
3
3
3
3
Missing
4
1
4
1
4
1
1
Abbreviation:  n/a, not applicable.
Note:  If the start date imputation leads to a start date that is after the stop date, then do not impute the start date.
1 = impute the date of Day 0.
2 = impute the first of the month.
3 = impute January 1 of the year.
4 = impute January 1 of the stop year.
I 
I 
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Imputation rules for partial or missing death dates:
•
If death year and month are available, but day is missing:
If mmyyyy for the last date known to be alive = mmyyyy for death date, set death date to 
the day after the last date known to be alive.
If mmyyyy for the last date known to be alive < mmyyyy for death date, set death date to 
the first day of the death month.
If mmyyyy for last date known to be alive > mmyyyy for death date, data error and do 
not impute.
•
If both month and day are missing for death date or a death date is completely missing, do 
not impute, and censor the subject survival time at the analysis data cutoff date or the last 
date known to be alive, whichever is later.


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Appendix 2.
Sample Adverse Event Table Layouts
Sample Adverse Event (AE) Summary Layout 1:  All AE summaries listed in Section 9.6.1 
will be provided in format 1 (“Gr 1” and “Gr 2” columns are not needed for “Grade 3 or higher” 
summary tables).  The preferred terms will be sorted by descending order of frequency of the 
“Any” column.
Table 2.
Subject Incidence of <AE Descriptor> AEs by Preferred Term 
(Worst Grade)
Any
Gr 1
Gr2
Gr 3
Gr 4
Gr 5
Any <AE descriptor> adverse 
event – n(%)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
Preferred term 1
XX (X)
XX (X) 
XX (X)
XX (X)
XX (X)
XX (X)
Preferred term 2
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
Abbreviations:  AE, adverse event; Gr, Grade.
Sample Adverse Event Summary Layout 2:  AE summaries may also be provided in format 2 
(“Gr 1” and “Gr 2” columns are not needed for “Grade 3 or higher” summary tables).  The 
system organ classes and preferred terms will be sorted by alphabetical order of system organ 
class and descending incidence of preferred term within each system organ class.
Table 3.
Subject Incidence of <AE Descriptor> AEs by System Organ Class 
and Preferred Term (Worst Grade)
Any
Gr 1
Gr 2
Gr 3
Gr 4
Gr 5
Any <AE descriptor> adverse 
event – n(%)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
System Organ Class 1
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
     Preferred term 1
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
     Preferred term 2
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
System Organ Class 2
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
…
Abbreviations:  AE, adverse event; Gr, Grade.


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KTE-C19-102 (ZUMA-2)
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Appendix 3.
Derivation of Time to Event Endpoints and Last Date Known to Be 
Alive
Additional detail on the derivations of duration of response (DOR), duration of response to 
retreatment (DORR), progression-free survival (PFS), and overall survival (OS) is provided 
below.
1) DOR
DOR is defined only for subjects who experience an objective response (CR or PR) and is the 
time from the first objective response to disease progression or death.  Response and progression 
may be defined per Central Read or Investigator Read. Data from retreatment period will not be 
included for analysis.  Subjects not meeting the criteria for progression or death by the analysis 
data cutoff date will be censored at their last evaluable disease assessment date.  DOR will be 
derived using disease assessments obtained on study prior to initiation of new anti-cancer 
therapy.  The DOR for subjects who undergo stem cell transplant (SCT) while in remission will 
be censored at the last evaluable disease assessment date prior to SCT; the DOR for subjects that 
undergo other new anti-cancer therapies in the absence of documented relapse will be censored 
at the last evaluable disease assessment prior to the new anti-cancer therapies. A sensitivity 
analysis will be conducted in which disease assessments and death information obtained after 
SCT are included in the derivation of duration of response.  
Table 4.
Primary Analysis of DOR
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression prior to initiation of new 
anti-cancer therapy (including SCT)
Event
Progression date
Death without documented disease progression 
and without new anti-cancer therapy (including 
SCT)
Event
Death date
Remain in response without new anti-cancer 
therapy (including SCT) 
Censored
Last evaluable disease assessment 
date
Initiated new anti-cancer therapy (including SCT) 
prior to documented progression or death
Censored
Last evaluable disease assessment 
date prior to initiation of new therapy 
including SCT
Remain in response without new anti-cancer 
therapy (including SCT) until withdrawal of 
consent or loss to follow-up
Censored
Last evaluable disease assessment 
date 
Abbreviations:  DOR, duration of response; SCT, stem cell transplant. 


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Table 5.
Sensitivity Analysis of DOR (to include data after SCT post study 
treatment)
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression after SCT, but prior to other 
new anti-cancer therapy
Event
Progression date
Death after SCT without documented progression 
and other new anti-cancer therapy
Event
Death date
Remain in response after SCT without other new 
anti-cancer therapy
Censored
Last evaluable disease assessment 
date after SCT
Remain in response after SCT prior to other 
initiated new anti-cancer therapy
Censored
Last evaluable disease assessment 
date after SCT but prior to other 
initiated new anti-cancer therapy
For subjects without SCT and all the other circumstances, follow the same as the “Primary Analysis of DOR.”
Abbreviations:  DOR, duration of response; SCT, stem cell transplant. 
2) DORR
DORR is defined the same as DOR, except that the definition applies to the response after 
KTE-X19/axicabtagene ciloleucel retreatment.  
3) PFS
PFS is defined as the time from the anti-CD19 CAR T cells infusion date to the date of disease 
progression or death from any cause.  Progression may be defined per Central Read or 
Investigator Read. For PFS analysis with the full analysis set in which enrolled but not treated 
subjects are included, the PFS time will be calculated as the time from the enrollment date to the 
date of disease progression or death from any cause. Data from retreatment period will not be 
included for analysis.  Subjects alive and not meeting the criteria for progression by the analysis 
data cutoff date will be censored at their last evaluable disease assessment date.  PFS will be 
derived using disease assessments obtained on study prior to initiation of new anti-cancer 
therapy (including SCT).  The PFS for subjects who undergo SCT while in remission will be 
censored at the last evaluable disease assessment date prior to SCT; the PFS for subjects that 
undergo other new anti-cancer therapies in the absence of documented relapse will be censored 
at the last evaluable disease assessment prior to the new anti-cancer therapies. A sensitivity 
analysis will be conducted in which disease assessments and death information obtained after 
SCT are included in the derivation of PFS. 


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Table 6.
Primary Analysis of PFS
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression prior to initiation of new 
anti-cancer therapy (including SCT)
Event
Progression date
Death without documented disease progression 
and without new anti-cancer therapy (including 
SCT)
Event
Death date
Remain in response and alive without new 
anti-cancer therapy (including SCT) 
Censored
Last evaluable disease assessment 
date
Initiated new anti-cancer therapy (including SCT) 
prior to documented progression or death
Censored
Last evaluable disease assessment 
date prior to initiation of new therapy 
including SCT.  If no evaluable 
disease assessment is available, then 
censor at anti-CD19 CAR T cells 
infusion date
Remained in response without new anti-cancer 
therapy (including SCT) until withdrawal of 
consent or loss to follow-up 
Censored
Last evaluable disease assessment 
date.  If no evaluable disease 
assessment is available, then censor 
at anti-CD19 CAR T cells infusion 
date
Subject enrolled and treated with anti-CD19 CAR 
T cells but the disease assessment has not been 
done
Censored
Anti-CD19 CAR T cells infusion 
date
Abbreviations:  PFS, progression-free survival; SCT, stem cell transplant.
Table 7.
Sensitivity Analysis of PFS
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression after SCT, but prior to other 
new anti-cancer therapy
Event 
Progression date
Death after SCT without documented progression 
and other new anti-cancer therapy
Event
Death date
Remain in response after SCT without other new 
anti-cancer therapy
Censored
Last evaluable disease assessment 
date after SCT
Remain in response after SCT prior to other 
initiated new anti-cancer therapy
Censored
Last evaluable disease assessment 
date after SCT but prior to other 
initiated new anti-cancer therapy
For subjects without SCT and all the other circumstances, follow the same derivation rule as the “Primary 
Analysis of PFS.”
Abbreviations:  PFS, progression-free survival; SCT, stem cell transplant.
4) OS


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OS is defined as the time from the anti-CD19 CAR T cells infusion to the date of death from any 
cause. For OS analysis with the full analysis set, the OS time will be calculated as the time from 
the enrollment date to the date of death from any cause. Subjects who have not died by the 
analysis data cutoff date will be censored at the last date known to be alive or the data cutoff 
date, whichever is earlier.
Table 8.
Analysis of OS
Circumstance
Event/Censored
Date of Event/Censoring
Death before data cutoff date for analysis
Event
Date of death
Death after data cutoff date for analysis
Censored
Data cutoff date
Known to be alive after data cutoff date for 
analysis
Censored
Data cutoff date
Alive up through data cutoff date and no further 
information available after data cutoff date
Censored
Last date known to be alive 
Full withdrawal of consent or lost to follow-up 
prior to data cutoff date
Censored
Last date known to be alive 
Abbreviation:  OS, overall survival.
5) Last Date Known to be Alive
The last date known to be alive with be derived by obtaining the maximum complete date among 
the following data modules:
•
Start date of AE
•
Leukapheresis dates
•
Bridging therapy administration dates
•
Conditioning chemo administration dates
•
anti-CD19 CAR T cells infusion dates
•
Computerized tomography (CT) scan dates
•
Positron emission tomography (PET) scan dates
•
Clinical symptoms of lymphoma assessment dates
•
Target lesion assessment
•
Non-target lesion assessment
•
New lesion assessment
•
Other tumor assessment dates (Bone marrow and spleen assessments)
•
Disease response assessment


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•
Long-term follow-up subject status date where status =  alive
•
End of treatment disposition where status is not equal to death, lost to follow-up
•
End of Month 3 disposition where status is not equal to death, lost to follow-up
•
End of study data where end of study reason is not equal to death, lost to follow-up


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Final
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Appendix 4.
Derivation of Simplified Mantle Cell Lymphoma International 
Prognostic Index 
The simplified Mantle Cell Lymphoma International Prognostic Index (s-MIPI) will be derived 
as described in Hoster {Hoster 2008}. 
Table 9.
Simplified Mantle Cell Lymphoma International Prognostic Index
Points
Age, yr
ECOG
LDH, ULN
WBC, 109/L
0
< 50
0 to 1
< 0.67
< 6.700
1
50 to 59
NA
0.67 to 0.99
6.700 to 9.999
2
60 to 69
2 to 4
1.000 to 1.49
10.000 to 14.999
3
≥ 70
NA
≥ 1.5000
≥ 15.000
Abbreviations:  ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NA, not applicable; ULN, upper 
limit of normal; WBC, white blood count; yr; year.
For each prognostic factor, 0 to 3 points will be given to each subject and points will be summed 
up to a maximum of 11 points.  Subjects with 0 to 3 points in summary will be classified as low 
risk, subjects with 4 to 5 points as intermediate risk, and subjects with 6 to 11 points as high risk.  
Eastern Cooperative Oncology Group (ECOG) performance status will be weighted with 2 points 
if subjects are unable to work or bedridden (ECOG 2 to 4).  Lactate dehydrogenase (LDH) will 
be weighted according to the ratio to the upper limit of normal.  Thus, for an upper limit of 
normal of 240 U/L, the cutpoints will be 180 U/L, 240 U/L, and 360 U/L, for example.
That is, Simplified Mantle Cell Lymphoma International Prognostic Index (s-MIPI) score = sum 
of the points for age, ECOG performance status, LDH, and white blood count from the above 
table.  The s-MIPI score can be classified into 3 risk categories as follows.
Table 10.
Risk Category Based on s-MIPI
s-MIPI score
Risk Category
0 to 3
Low risk
4 to 5
Intermediate risk
6 to 11 
High risk
Abbreviation:  s-MIPI, simplified Mantle Cell Lymphoma International Prognostic Index.

Prot_000.pdf: 
Protocol Title: 
A Phase 2 Multicenter Study Evaluating the Efficacy ofKTE-X19 in Subjects with 
Relapsed/R.efractory Mantle Cell Lymphoma (ZUMA-2) 
Protocol Number: 
K1E-C19-102 
IND Number: 
016675 
EudraCT Number: 
2015-005008-27 
Clinical Stndy Sponsor: 
Kite Pharma, Inc. 
2400 Broadvw,y 
Santa Monica, CA 90404 
United States of America 
Key Sponsor Contact: 
PPD 
I 
Senior Director, Clinical Development 
PPD 
PPD 
P one:PPD 
Email:PPD 
I 
[PPD 
J 
StuclyMan!lger, CfinicOperations 
PPD -J 
P one:PPD 
Email:PPD 
I 
Version: 
Amendment# 6 
Date: 
29 October 2018 
CONFIDENTIALITY NOTICE 
This document contains proprietary and confidential information of Kite Pharma Inc., a wholly 
owned subsidiary of Gilead Sciences, Inc. The information must not be disclosed to any 
third party without the prior written consent of Kite Pharma, Inc. Questions regarding how this 
document should be used or the conduct of the clinical trial should be directed to the key sponsor 
contacts. 


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
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29 October 2018
INVESTIGATOR’S AGREEMENT
I have read the attached protocol titled A Phase 2 Multicenter Study Evaluating the Efficacy of 
KTE-X19 in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2) dated
29 October 2018 and agree to abide by all provisions set forth therein.
I agree to comply with the International Conference on Harmonisation Tripartite Guideline on 
Good Clinical Practice and applicable national or regional regulations and guidelines.
I agree and will ensure that financial disclosure statements will be completed by:

Me (including, if applicable, my spouse, legal partner, and dependent children)

Sub-Investigators (including, if applicable their spouse, legal partner, and dependent 
children) at the start of the study and for up to one year after the study is completed.
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the clinical investigation without prior written consent 
from Kite Pharma, Inc.
_____________________________________________________________________
Signature
______________________________________________________________________
Name of investigator
_____________________________________________________________________
Date


KTE-C19-102 
Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
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PROTOCOL SYNOPSIS
Title: 
A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects with 
Relapsed/Refractory Mantle Cell Lymphoma (ZUMA-2)
Indication:
The treatment of adult subjects with relapsed/refractory mantle cell lymphoma
(r/r MCL).
Study Design:
Study KTE-C19-102 is a Phase 2, multicenter, open-label study evaluating the efficacy 
of KTE-X19 in subjects with r/r MCL.
Cohort 1 will enroll and treat up to approximately 90 subjects with cyclophosphamide 
and fludarabine conditioning chemotherapy, followed by a target dose of 2 x 106 anti‑
CD19 CAR T cells per kg body weight. This cohort will include at least 60 but up to 
approximately 80 subjects treated with KTE-X19 (referred to as KTE-X19 subjects in 
this document) and 10 subjects treated with axicabtagene ciloleucel (referred to as 
axicabtagene ciloleucel subjects in this document). The KTE-X19 subjects in this 
cohort will form the basis for hypothesis testing on the primary endpoint.  
Cohort 2 will enroll and treat up to 40 KTE-X19 subjects with cyclophosphamide and 
fludarabine conditioning chemotherapy, followed by a target dose of 0.5 x 106 anti-
CD19 chimeric antigen receptor (CAR) T cells per kg body weight.
Each subject will proceed through the following study periods:

Screening 

Enrollment/Leukapheresis 

Bridging therapy if applicable

Conditioning chemotherapy 

Investigational product (IP) treatment 

Post-treatment assessment 

Long-term follow-up period
For study requirements assigned to each study period, refer to Section 7 for details.   
Study Objectives:
The primary objective is to evaluate the efficacy of KTE-X19, as measured by 
objective response rate (ORR), in subjects with r/r MCL. Secondary objectives will 
include assessing the safety and tolerability of KTE-X19, additional efficacy endpoints, 
and change in the European Quality of Life-5 Dimensions (EQ-5D) scores from 
baseline to Month 6.
Hypothesis:
This study uses an open-label 2-cohort design.
Among the Cohort 1 KTE-X19 subjects, with a target 50% response rate per 
independent review, an alternative hypothesis will be tested against a null hypothesis 
that the response rate is 25% or less. The hypothesis is that the ORR to KTE-X19 per
independent review is significantly greater than 25% in Cohort 1 KTE-X19 subjects.
No hypothesis will be tested in Cohort 1 axicabtagene ciloleucel subjects and Cohort 2
KTE-X19 subjects. Exploratory analyses will be conducted on the data collected from 
these subjects.


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Primary Endpoint:
ORR (complete response [CR] + partial response [PR]) per the Lugano Classification
(Cheson et al, 2014) per Independent Radiology Review Committee (IRRC) review
Secondary 
Endpoints:

Duration of response 

Best objective response (BOR)

ORR as determined by study investigators

Progression-free survival

Overall survival 

Incidence of adverse events (AEs) and clinically significant changes in laboratory 
values

Incidence of anti-CD19 CAR antibodies

Levels of anti-CD19 CAR T cells in blood

Levels of cytokines in serum

Changes over time in the EQ-5D scale score and visual analogue scale score
Exploratory 
Endpoints:
Sample Size:

Up to approximately 130 will be enrolled in the study: 

90 subjects in Cohort 1 (10 axicabtagene ciloleucel subjects and approximately 
80 KTE-X19 subjects) at 2 x 106 anti‑CD19 CAR T cells per kg body weight 

Up to 40 KTE-X19 subjects in Cohort 2 at 0.5 x 106 anti‑CD19 CAR T cells 
per kg body weight
Study Eligibility:
Refer to Section 5 for a detailed list of inclusion and exclusion criteria.
Treatment:
Bridging Therapy

At the discretion of the investigator, bridging therapy may be considered for 
subjects particularly with high disease burden at screening (eg, > 25% marrow 
involvement or ≥ 1000 leukemic phase mantle cells/mm3 in the peripheral 
circulation).  

Bridging therapy is allowed with (1) dexamethasone or other corticosteroid,
(2) ibrutinib, or (3) acalabrutinib.

If prescribed, bridging therapy must be administered after leukapheresis and 
completed at least 5 days prior to initiating conditioning chemotherapy. 

Refer to Section 6 for dosing and further details.
Conditioning Chemotherapy Treatment:

KTE-X19 or axicabtagene ciloleucel is administered after a conditioning 
chemotherapy regimen consisting of fludarabine 30 mg/m2/day and 
cyclophosphamide 500 mg/m2/day, administered x 3 days. Refer to Section 6 for 
chemotherapy treatment details.
CCI


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Investigational Product:

KTE-X19 or axicabtagene ciloleucel treatment consists of a single infusion of 
CAR-transduced autologous T cells administered intravenously at a target dose of 2 
x 106 anti-CD19 CAR T cells/kg (Cohort 1) or 0.5 x 106 anti-CD19 CAR T cells/kg 
(Cohort 2).  Under circumstances where subjects initially respond and subsequently 
relapse, subjects may be eligible for a second course of conditioning chemotherapy 
and KTE-X19 or axicabtagene ciloleucel. Refer to Section 6 for treatment details 
and Section 7.12.10 for retreatment details.
Procedures:
At specific time points as outlined in the schedule of assessments, subjects will undergo 
the following assessments/procedures: collection of informed consent; general medical 
history, including previous treatments for MCL; physical exam, including vital signs 
and performance status; neurological assessments; blood draws for complete blood 
count (CBC), chemistry panels, cytokines, C-reactive protein, lymphocyte subsets, anti-
CD19 CAR antibodies, replication-competent retrovirus (RCR), and anti-CD19 CAR 
T cells analysis. Women of childbearing potential will undergo a urine or serum 
pregnancy test. 
Subjects will also undergo a baseline electrocardiogram (ECG), echocardiogram 
(ECHO), brain magnetic resonance image (MRI), a positron emission tomography-
computed tomography (PET-CT), bone marrow aspirate/biopsy, and leukapheresis. 
Routinely throughout the conduct of the study, subjects will be asked to complete the 
EQ-5D questionnaire, report concomitant medications and AEs, and will have their 
disease assessed.
Data Safety 
Monitoring Board:
An independent Data Safety Monitoring Board (DSMB) will review safety and/or 
efficacy data 4 times during this study. The DSMB will first meet to review safety data 
when 10 subjects in Cohort 1 have been enrolled and treated with anti-CD19 CAR T
cells and followed for 30 days. The DSMB will meet for the second time to review 
both safety and efficacy data after 20 subjects in Cohort 1 have been enrolled, treated,
and have had the opportunity to complete the 3-month disease assessment.  The DSMB 
will meet for the third time to review both safety and efficacy data after 10 subjects in 
Cohort 2 have been enrolled, treated, and have had the opportunity to be followed for 
30 days. The DSMB will meet for the fourth time to review safety data after 44 subjects 
in Cohort 1 have been enrolled, treated, and have had the opportunity to be followed for 
at least 30 days, with focus on the safety data from the 6 KTE-X19 subjects treated 
most recently in this cohort. The DSMB will be chartered to make trial conduct 
recommendations based on an analysis of risk vs benefit.  The DSMB may meet more 
often as needed.  Refer to Section 9.10 and Section 9.11.
Statistical 
Considerations:
This study uses an open-label, 2-cohort design. Among the Cohort 1 KTE-X19
subjects, with a target 50% response rate per independent review, an alternative 
hypothesis will be tested against a null hypothesis that the response rate is 25% or less. 
For the test of efficacy in the Cohort 1 KTE-X19 subjects, this study has at least
96% power to distinguish between an active therapy with a 50% true response rate from 
a therapy with a response rate of 25% or less with a 1-sided alpha level of 0.025. No 
hypothesis will be tested on Cohort 1 axicabtagene ciloleucel subjects and on Cohort 2.
Four interim analyses will be performed in Cohort 1, and 1 interim analysis will be 
performed in Cohort 2.  One primary analysis will be performed after 60 Cohort 1 
KTE-X19 subjects have been enrolled and treated and have had the opportunity to be
assessed for response 6 months after the Week 4 disease assessment.


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
Cohort 1 interim analysis 1 will be conducted after 10 subjects in Cohort 1 have 
been enrolled and treated with anti-CD19 CAR T cells and followed for 30 days.  
This interim analysis will be for safety only. 

Cohort 1 interim analysis 2 will be conducted after 20 subjects in Cohort 1 
(Section 10.5) have been enrolled and treated with anti-CD19 CAR T cells and 
have had the opportunity to be evaluated for response 3 months after the 
investigational product (IP) infusion. This interim analysis will be for safety and 
efficacy (futility only).

Cohort 1 interim analysis 3 will occur after 38 subjects treated with anti-CD19 
CAR T cells in Cohort 1 have had the opportunity to be assessed for response 
6 months after the IP infusion.

Cohort 1 interim analysis 4 will be conducted after 44 subjects in Cohort 1 have 
been enrolled and treated with anti-CD19 CAR T cells and have had the 
opportunity to be followed for at least 30 days after the IP infusion.  This interim 
analysis will assess safety only, with focus on the KTE-X19 subjects treated most 
recently in this cohort.  

Cohort 2 interim analysis will be conducted after 10 subjects in Cohort 2 have been 
enrolled and treated with KTE-X19 and have had the opportunity to be followed 
for 30 days after the KTE-X19 infusion.  This interim analysis will assess safety 
and efficacy.  
The primary analysis will occur after 60 KTE-X19 subjects in the modified intent-to-
treat (mITT) set of Cohort 1 have been enrolled and treated with KTE-X19 and have 
had the opportunity to be assessed for response 6 months after the Week 4 disease 
assessment.


KTE-C 19-1 02 
Clinical Protocol 
Kite Pharma, Inc. 
Figure 1. 
Study Schema 
Conditioning Chemotherafil'. 
Investigational Product (IP) 
'O 
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Period 
Treatment Period 
0 
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Study KTE-C 19-102 is a Phase 2, multi center, open-label study evaluating the efficacy of KTE-Xl9 in subjects with relapsed/refractory mantle cell 
lymphoma (r/r MCL). 
Up to approximately 130 subjects with r/r MCL will be enrolled into 2 separate cohorts designated as Cohort 1 and Cohort 2. 
• 
Cohort 1 will enroll and treat 90 subjects at a target dose of 2 x 106 anti-CD 19 CAR T cells/kg, including 10 axicabtagene ciloleucel subjects 
and approximately 80 KTE-X19 subjects. 
• 
Cohort 2 will enroll and treat up to approximately 40 KTE-Xl9 subjects at a target dose of0.5 x 106 anti-CD19 CART cells/kg. 
Final 
CONFIDENTIAL 
Page 7 of92 
29 October 2018 


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TABLE OF CONTENTS
INVESTIGATOR’S AGREEMENT.............................................................................................................................2
PROTOCOL SYNOPSIS ..............................................................................................................................................3
TABLE OF CONTENTS ..............................................................................................................................................8
LIST TABLES.............................................................................................................................................................11
LIST OF FIGURES.....................................................................................................................................................11
LIST OF ABBREVIATIONS......................................................................................................................................12
1.
OBJECTIVES.....................................................................................................................................................15
2.
DISEASE BACKGROUND AND RATIONALE..............................................................................................16
2.1.
First-line Therapy...................................................................................................................................16
2.2.
Therapy for Relapsed/Refractory MCL .................................................................................................17
2.3.
CD19 and Expression.............................................................................................................................19
2.4.
Anti-CD19 CAR T-cell Product.............................................................................................................19
2.4.1.
Axicabtagene Ciloleucel.......................................................................................................20
2.4.2.
KTE-X19..............................................................................................................................21
2.5.
Prior Experience with KTE-X19 and Other Anti-CD19 CAR T Cells...................................................21
2.6.
KTE-X19................................................................................................................................................24
3.
STUDY DESIGN................................................................................................................................................25
3.1.
General Study Design ............................................................................................................................25
3.2.
Participating Sites...................................................................................................................................26
3.3.
Number of Subjects................................................................................................................................26
3.4.
Replacement of Subjects........................................................................................................................26
3.5.
Study Duration .......................................................................................................................................26
3.5.1.
Study Duration for Individual Subjects................................................................................26
3.5.2.
Completion of Study ............................................................................................................26
4.
SUBJECT SCREENING AND ENROLLMENT...............................................................................................27
5.
SUBJECT ELIGIBILITY ...................................................................................................................................28
5.1.
Inclusion Criteria....................................................................................................................................28
5.2.
Exclusion Criteria...................................................................................................................................29
6.
PROTOCOL TREATMENT ..............................................................................................................................31
6.1.
Treatment Terminology..........................................................................................................................31
6.2.
Study Treatment.....................................................................................................................................31
6.2.1.
Bridging Therapy .................................................................................................................31
6.2.2.
Conditioning Chemotherapy ................................................................................................31
6.2.3.
KTE-X19..............................................................................................................................32
6.2.4.
Concomitant Therapy...........................................................................................................33
6.2.5.
Excluded Medications..........................................................................................................34
6.2.6.
Subsequent Therapy .............................................................................................................34
6.3.
Study Treatment Schedule .....................................................................................................................34
6.3.1.
Leukapheresis (Within Approximately 5 Days of Eligibility 
Confirmation).......................................................................................................................34
6.3.2.
Bridging Therapy (Administered after Leukapheresis and Completed at 
Least 5 Days Prior to Initiating Conditioning Chemotherapy).............................................35
6.3.3.
Cyclophosphamide and Fludarabine (Days –5 Through –3 Before 
Infusion of anti-CD19 CAR T cells)....................................................................................35


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6.3.4.
KTE-X19 or axicabtagene ciloleucel (Day 0, after Fludarabine and 
Cyclophosphamide)..............................................................................................................36
6.4.
Toxicity Management ............................................................................................................................37
7.
STUDY PROCEDURES ....................................................................................................................................38
7.1.
Informed Consent...................................................................................................................................38
7.2.
Demographic Data .................................................................................................................................38
7.3.
Medical and Treatment History..............................................................................................................38
7.4.
Physical Exam, Vital Signs, Performance Status, and European Quality of Life-5 Dimensions ...........39
7.5.
Neurological Assessment .......................................................................................................................39
7.6.
Bone Marrow Biopsy .............................................................................................................................40
7.7.
Lumbar Puncture....................................................................................................................................41
7.8.
Disease Response Assessment ...............................................................................................................41
7.9.
Cardiac Function ....................................................................................................................................42
7.10.
Magnetic Resonance Imaging ................................................................................................................42
7.11.
Laboratory..............................................................................................................................................42
7.11.1.
Biomarkers ...........................................................................................................................43
7.12.
Description of Study Periods..................................................................................................................45
7.12.1.
Screening..............................................................................................................................45
7.12.2.
Rescreening..........................................................................................................................46
7.12.3.
Enrollment/Leukapheresis....................................................................................................47
7.12.4.
Bridging Therapy .................................................................................................................48
7.12.5.
Conditioning Chemotherapy Period.....................................................................................48
7.12.6.
Investigational Product Treatment Period............................................................................50
7.12.7.
Requirements to Work Up Potential Infectious and/or Inflammatory 
States....................................................................................................................................52
7.12.8.
Post-treatment Assessment Period .......................................................................................53
7.12.9.
Long-term Follow-up Period................................................................................................55
7.12.10.
Retreatment ..........................................................................................................................56
8.
SUBJECT WITHDRAWL..................................................................................................................................61
8.1.
Reasons for Removal from Treatment ...................................................................................................61
8.2.
Reasons for Removal from Study ..........................................................................................................62
9.
SAFETY REPORTING......................................................................................................................................63
9.1.
AEs.........................................................................................................................................................63
9.2.
Reporting of AEs....................................................................................................................................63
9.3.
Definition of SAEs.................................................................................................................................64
9.4.
Reporting of SAEs and Non-serious CRS Events Grade ≥ 3.................................................................65
9.5.
Reporting Deaths....................................................................................................................................66
9.6.
Diagnosis Versus Signs and Symptoms .................................................................................................66
9.7.
Pregnancy and Lactation........................................................................................................................66
9.8.
Hospitalization and Prolonged Hospitalization......................................................................................67
9.9.
Abnormal Vital Signs Values.................................................................................................................67
9.10.
Data Safety Monitoring Board ...............................................................................................................68
9.11.
Criteria to Pause Enrollment ..................................................................................................................68
10.
STATISTICAL CONSIDERATIONS................................................................................................................69
10.1.
Hypothesis..............................................................................................................................................69
10.2.
Study Endpoints .....................................................................................................................................69
10.2.1.
Primary.................................................................................................................................69
10.2.2.
Secondary.............................................................................................................................69
10.2.3.
Exploratory Endpoints..........................................................................................................70
10.3.
Sample Size Considerations...................................................................................................................70
10.4.
Statistical Assumptions ..........................................................................................................................71


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10.5.
Analysis Subsets.....................................................................................................................................71
10.6.
Access to Individual Subject Treatment Assignments ...........................................................................72
10.7.
Interim Analysis.....................................................................................................................................72
10.7.1.
Interim Analysis and Early Stopping Rules .........................................................................72
10.7.2.
Safety Interim Analysis........................................................................................................72
10.7.3.
Efficacy Interim Analysis.....................................................................................................72
10.7.4.
Other Interim Analysis .........................................................................................................73
10.8.
Planned Methods of Analysis.................................................................................................................73
10.8.1.
ORR......................................................................................................................................73
10.8.2.
Best Objective Response......................................................................................................73
10.8.3.
DOR .....................................................................................................................................74
10.8.4.
PFS.......................................................................................................................................74
10.8.5.
OS.........................................................................................................................................74
10.8.6.
Safety....................................................................................................................................74
10.8.7.
Long-term Data Analysis .....................................................................................................74
11.
REGULATORY OBLIGATIONS......................................................................................................................75
11.1.
Independent Review Board/Independent Ethics Committee..................................................................75
11.2.
Subject Confidentiality...........................................................................................................................75
11.3.
Investigator Signatory Obligations.........................................................................................................75
12.
PROTOCOL AMENDMENTS AND TERMINATION ....................................................................................76
13.
STUDY DOCUMENTATION AND ARCHIVE ...............................................................................................77
14.
STUDY MONITORING AND DATA COLLECTION.....................................................................................78
15.
PUBLICATION..................................................................................................................................................79
16.
COMPENSATION .............................................................................................................................................80
17.
REFERENCES ...................................................................................................................................................81
18.
APPENDIX.........................................................................................................................................................86
18.1.
Appendix 1:  Revised IWG Response Criteria for Malignant Lymphoma.............................................86
18.1.1.
Complete Response..............................................................................................................86
18.1.2.
Partial Response ...................................................................................................................86
18.1.3.
Stable Disease ......................................................................................................................87
18.1.4.
Progressive Disease..............................................................................................................87
18.2.
Appendix 2:  Lugano Classification.......................................................................................................88
18.2.1.
Complete Response..............................................................................................................88
18.2.2.
Complete Radiologic Response............................................................................................88
18.2.3.
Partial Response ...................................................................................................................89
18.2.4.
Stable Disease ......................................................................................................................90
18.3.
Appendix 3:  Monitoring of Subjects After IP Administration per Country Regulatory 
Agencies.................................................................................................................................................92


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LIST TABLES
Table 1.
Treatment Outcomes in First-line MCL .................................................................................17
Table 2.
Outcomes with Available Therapies in r/r MCL ....................................................................19
Table 3.
Treatment Outcomes in r/r MCL After Progressing on Ibrutinib ...........................................19
Table 4.
Subject Disposition, Full Analysis Set ...................................................................................21
Table 5.
Overall Summary of AEs, Safety Analysis Set ......................................................................22
Table 6.
Subject Listing of Deaths, Safety Analysis Set ......................................................................23
Table 7.
Subject Incidence of Frequent (≥ 10%) Grade 3 or Higher Treatment-emergent 
Adverse Events by Preferred Terms and Worse Grade, Safety Analysis Set (n = 28) ...........23
Table 8.
Schedule of Assessments (1 of 2)...........................................................................................58
Table 9.
Schedule of Assessment (2 of 2) ............................................................................................60
Table 10.
5-point Scale (5PS).................................................................................................................88
LIST OF FIGURES
Figure 1.
Study Schema...........................................................................................................................7
Figure 2.
Anti-CD19 Chimeric Antigen Receptor.................................................................................20
Figure 3.
Bone Marrow Assessment Schema ........................................................................................40


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LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
Adverse event
alloSCT
Allogeneic stem cell transplant
ALT
Alanine aminotransferase
ANC
Absolute neutrophil count
AST
Aspartate aminotransferase
AUC
Area under curve
autoSCT
Autologous stem cell transplant
BTKi
Bruton’s tyrosine kinase inhibitor
CAR
Chimeric antigen receptor 
CBC
Complete blood count
CLL
Chronic lymphocytic leukemia
CNS
Central nervous system
CPF
Cell processing facility
CR
Complete response
CRF
Case report form
CRO
Contract Research Organization
CRP
C-reactive protein
CRS
Cytokine release syndrome
CSF
Cerebrospinal fluid
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DOR
Duration of response
DSMB
Data Safety Monitoring Board
ECG
Electrocardiogram
ECHO
Echocardiogram
ECOG
Eastern Cooperative Oncology Group
EQ-5D
European Quality of Life-5 Dimensions
GCP
Good Clinical Practices
GOT
Glutamic-oxaloacetic transaminase
GPT
Glutamic-pyruvic transaminase
HEENT
Head, ears, eyes, nose, and throat
HIV
Human immunodeficiency virus


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Abbreviation
Definition
HLH
Hemophagocytic lymphohistiocytosis
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Conference on Harmonisation
ID
Identification
IP
Investigational product
IRB/IEC
Institutional Review Board/Independent Ethics Committee
IRRC
Independent Radiology Review Committee 
IV
Intravenous
IWG
International Working Group 
LDH
Lactate dehydrogenase
LTFU
Long-term follow-up
LVEF
Left ventricular ejection fraction
MCL
Mantle cell lymphoma
mITT
Modified intent-to-treat
MMSE
Mini-Mental Status Exam
MRI
Magnetic resonance imaging
NCI
National Cancer Institute
NHL
Non-Hodgkin lymphoma
ORR
Objective response rate
OS
Overall survival
PBMC
Peripheral blood mononuclear cell
PCR
Polymerase chain reaction
PD
Progressive disease
PET-CT
Positron emission tomography-computed tomography
PFS
Progression-free survival
PR
Partial response
qPCR
Quantitative polymerase chain reaction
RCR 
Replication-competent retrovirus
r/r
Relapsed/refractory
SAE
Serious adverse event
SCT
Stem cell transplant
SD
Stable disease


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Abbreviation
Definition
SOA
Schedule of assessment
SUSAR
Suspected unexpected serious adverse reaction 
TEAE
Treatment-emergent adverse event
VAS
Visual analogue scale
WBC
White blood cell


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1.
OBJECTIVES
The primary objective is to evaluate the efficacy of KTE-X19, as measured by objective 
response rate (ORR), in subjects with relapsed/refractory (r/r) mantle cell lymphoma (MCL). 
Secondary objectives will include assessing the safety and tolerability of KTE-X19, additional 
efficacy endpoints, and the change in the European Quality of Life-5 Dimensions (EQ-5D)
scores from baseline to Month 6.


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2.
DISEASE BACKGROUND AND RATIONALE
Mantle cell lymphoma is an aggressive, generally incurable, B-cell malignancy, representing 
approximately 6% of non-Hodgkin lymphomas (NHLs). Approximately 4000  new cases are 
diagnosed yearly in the United States (Leukemia & Lymphoma Society 2014).  The lymphoma 
cells are thought to originate from naïve pregerminal center B cells within the mantle zone, and 
they typically express CD5, CD19, CD20, surface IgM, and surface IgD (Dreyling 2014), but not 
CD11c (Kraus et al, 2010).  More than 95% of MCLs carry translocation t(11;14)(q13;q32),
which places the cyclin D1 gene in proximity of the immunoglobulin heavy chain locus, 
resulting in overexpression of cyclin D1, which can be detected by cytogenetics or fluorescence 
in situ hybridization (National Comprehensive Cancer Network 2017).  Most patients are male, 
and the median age of diagnosis is 68 years (Fakhri and Kahl 2017).  Patients typically present 
with advanced lymphadenopathy, and also show extranodal involvement of the spleen, bone 
marrow, and gastrointestinal (GI) tract (Dreyling et al, 2014; Rajabi and Sweetenham 2015; 
National Comprehensive Cancer Network 2017; Vose 2017).  Prognosis varies based on clinical 
and laboratory parameters and can be estimated using the mantle cell international prognostic 
index.  This index uses the 4 independent prognostic factors of age, performance status, lactate 
dehydrogenase (LDH), and leukocyte count to classify patients as low risk (60% to 83% 5-year 
overall survival [OS]), intermediate (35% to 63% 5-year OS), or high risk (20% to 34% 5-year 
OS) (Hoster et al, 2008; Hoster et al, 2014).  
2.1.
First-line Therapy
Most patients require systemic therapy at the time of diagnosis.  First-line therapy for MCL 
typically includes chemotherapy in combination with a CD20 targeting antibody (Table 1). 
Combination regimens include rituximab with cyclophosphamide, doxorubicin vincristine, and 
prednisone (R-CHOP); rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP);
and bendamustine and rituximab (BR) (Lenz et al, 2005; Kluin-Nelemans  et al, 2012; Flinn et 
al, 2014).  Treatment intensification for younger patients with regimens, such as rituximab in 
combination with fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone 
(hyper-CVAD) alternating with high-dose methotrexate and cytarabine (MA) 
(R-HyperCVAD/MA) (Romaguera et al, 2005; Romaguera et al, 2010), or high-dose 
chemotherapy followed by autologous stem cell transplant (autoSCT) in first remission
(Dreyling et al, 2005), have led to improved outcomes at the expense of additional toxicity. 
Despite high initial response rates to these therapies, almost all patients eventually develop 
progressive disease. 


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Table 1.
Treatment Outcomes in First-line MCL
Regimen
N
Outcome
Reference
R-CHOP v CHOP
122
ORR1  94 v 75%;  CR 34 v 7%, 
mTTF = 21 v 14 m
(Lenz et al, 2005)
R-CHOP v R-FC
560
ORR 86 v 78%; CR 34 v 40%; 4 yr 
OS 62 v 47%
(Kluin-Nelemans et al, 
2012)
BR v R-CHOP/R-CVP
74
ORR 94 v 85%; CR 50 v 27%
(Flinn et al, 2014)
R-HyperCAD/MA
97
CR 77%, mTTF= 4.6 y
(Romaguera et al, 2005)
(Romaguera et al, 2010)
ASCT v IFN-α in first remission
122
mPFS 39 v 17m;  2 year OS 86 v 
82%
(Dreyling et al, 2005)
Abbreviations:  ASCT, autologous stem cell transplant; BR, bendamustine + rituximab; CHOP, cyclophosphamide + doxorubicin 
+ vincristine + prednisone; IFN-α, interferon-alpha; CR, complete response; R-CHOP, rituximab + cyclophosphamide + 
doxorubicin + vincristine + prednisone; R-CVP, rituximab + cyclophosphamide + vincristine + prednisone; R-FC, rituximab + 
fludarabine + cyclophosphamide; R-HyperCAD, rituximab + fractionated cyclophosphamide +  vincristine + doxorubicin + 
dexamethasone; m, month; MA, methotrexate + cytarabine; mPFS, median progression-free survival; mTTF, median time-to-
treatment failure; ORR, objective response rate; OS, overall survival; y, year.
2.2.
Therapy for Relapsed/Refractory MCL
There is no established paradigm for the treatment of r/r MCL.  Treatment options includes 
cytotoxic chemotherapy, proteasome inhibitors, immunomodulatory drugs, tyrosine kinase 
inhibitors, and stem cell transplant (SCT). The choice of regimen is influenced by prior therapy, 
comorbidities, and tumor chemosensitivity. 
Cytotoxic chemotherapy combination regimens used in r/r MCL include fludarabine, 
cyclophosphamide (FC), although this regimen is less efficacious in the relapsed setting than as a 
first-line treatment, and is associated with substantial toxicities (Cohen et al, 2001).  For patients 
with poorer fitness, less intensive therapies are considered based on first-line treatment data,
including rituximab alone, chlorambucil, cladribine, or thalidomide, usually in combination with 
rituximab, but these single cytotoxic agent-based regimens have limited efficacy compared to
multi-agent approaches (Foran et al, 2000; Kaufmann et al, 2004; Inwards et al, 2008; Sachanas 
et al, 2011).  
Stem cell transplant has a role in r/r MCL, although its use is limited to those patients who are 
younger and have good fitness.  AutoSCT is more commonly used than allogeneic, and, in 
eligible patients, results in approximately 25% to 35% event-free survival after 2 to 3 years of 
follow-up (Ketterer et al, 1997; Vose et al, 2000).  Allogeneic stem cell transplant (alloSCT) has 
been investigated in multiple single institution and registry studies in relapsed and refractory 
disease, including patients who have previously undergone autoSCT.  Results from these studies 
are variable, likely in part due to selection bias in single institution and registry based studies, but 
suggest approximately 25% of patients undergoing alloSCT achieve durable remissions if their 
disease is demonstrated to be chemosensitive prior to transplant (Rajabi and Sweetenham 2015). 


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However, in these studies, alloSCT has been associated with high morbidity and non-relapse 
mortality, mostly due to graft versus host disease and its complications and affecting 30% to 
40% of patients.
The agents bortezomib, lenalidomide, ibrutinib, and acalabrutinib have been approved in the 
United States within the last 10 years for the treatment of r/r MCL (see Table 2), and 
temsirolimus is approved in the EU. Bortezomib is an inhibitor of the 26S proteasome and was 
evaluated in a single‑arm, open-label, multicenter trial of 155 patients with r/r MCL who had 
received at least 1 prior therapy (Fisher et al, 2006).  Thirty-seven percent had disease refractory 
to the last treatment regimen.  The ORR based on independent radiologic review of computed 
tomography (CT) scans was 31%, including 6% complete responses.  The median duration of 
response (DOR) was 9.3 months, and the median time to progression was 6.1 months 
(bortezomib USPI).  The most common Grade 3 or greater toxicities were peripheral neuropathy 
(13%), fatigue (12%), and thrombocytopenia (11%).  
Lenalidomide, a second-generation thalidomide derivative, was studied in a single-arm, open-
label, multicenter, trial of 134 patients with r/r MCL (Goy et al, 2013).  Patients were required to 
have received prior treatment with an anthracycline or mitoxantrone, cyclophosphamide, 
rituximab, and bortezomib. Fifty-three percent had 4 or more prior therapies, 60% had disease 
refractory to bortezomib, and 29% had a prior autoSCT.  The ORR based on independent 
radiologic review of CT scans was 26%; 1% achieved a complete response (CR) (lenalidomide 
USPI).  The median DOR was 16.6 months, and the median progression-free survival (PFS) was 
4 months.  The most common Grade 3 or Grade 4 adverse events (AEs) were neutropenia (43%), 
thrombocytopenia (28%), anemia (11%), pneumonia (8%), and fatigue (7%). 
Ibrutinib is a covalent inhibitor of Bruton’s tyrosine kinase.  The safety and efficacy of ibrutinib 
was evaluated in a single-arm, open-label, multicenter, trial of 111 patients with r/r MCL who 
had received at least 1, but no more than 5 prior therapies (Wang et al, 2013). The ORR based 
on investigator review of CT scans was 68%, including 21% complete responses.  The median 
DOR was 17.5 months, and the median PFS was 13.9 months.  The most common Grade 3 or 
higher toxicities were neutropenia (16%), thrombocytopenia (11%), and diarrhea (6%).  
Despite available therapies, almost all patients with r/r MCL die from progressive disease (refer 
to Table 3).  Martin et al, conducted a large (n = 114) retrospective cohort study of response and 
survival in patients treated after primary or acquired ibrutinib resistance (Martin et al, 2016).  Of 
the 104 patients with data available, 73 patients underwent subsequent treatment after stopping 
ibrutinib, and 61 subjects were evaluable for efficacy.  Outcomes were poor, with an ORR of 
26%, CR rate of 7%, and median OS of 5.8 months. Cheah et al, reported similar results (ORR 
32% and median OS of 8.4 months) in a cohort of 31 patients (Cheah et al, 2015). There are 
limited other data on the efficacy of bortezomib, lenalidomide, or other agents in patients who
have progressed on ibrutinib therapy.  There is an urgent unmet need for new treatment options 
that can induce durable responses in a significant fraction of patients.  
Most recently, acalabrutinib, an oral Bruton’s tyrosine kinase inhibitor (BTKi), was approved in 
the US for the treatment of relapsed or refractory MCL (acalabrutinib USPI).  This agent was 
studied in an open-label, multicenter, Phase 2 study of 124 patients with MCL who had at least 
1 prior therapy (median 2 prior lines of therapy; range:  1 to 5 prior lines), and those who had


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previously been treated with any BTKi were excluded from the study (acalabrutinib USPI ; 
Wang et al, 2017).  Thus, this population was less heavily pretreated compared with patients in 
the trials of bortezomib, lenalidomide, and ibrutinib.  After a median follow-up of 15.2 months, 
the ORR was 81% and the CR rate was 40% (acalabrutinib USPI).  Among all treated patients, 
the medians for DOR, PFS, and OS were not reached, and the 12-month PFS and OS rates were 
67%, and 87%, respectively.  The most common Grade 3 and higher AEs were neutropenia 
(13 patients, 10%), anemia (11 patients, 9%), and pneumonia (6 patients, 5%) (Wang et al, 
2017).
Table 2.
Outcomes with Available Therapies in r/r MCL
Regimen
N
Outcome
Reference
Bortezomiba
155
ORR 31%;  CR 8%, DOR 9.3m
(Fisher et al, 2006)
Lenalidomideb
134
ORR 26%; CR 7%; DOR 16.6m
(Goy et al, 2013)
Ibrutinib
111
ORR 68%; CR 21%; DOR 17.5m
(Wang et al, 2013)
Acalabrutinib
124
ORR 81%; CR 40%; DOR NR
(Wang et al, 2017)
Abbreviations:  CR, complete response; DOR, duration of response; m, month; NR, no response; ORR, objective response rate.
a
Retrospective cohort studies of patients with primary or acquired ibrutinib resistant MCL treated with salvage therapy.  
b
Patients enrolled in this study had not failed ibrutinib.
Table 3.
Treatment Outcomes in r/r MCL After Progressing on Ibrutinib
N
Outcome
Reference
61
ORR 26%;  CR rate 7%, mOS 5.8m
(Martin et al, 2016)
31
ORR  32% 19% CR rate; mOS 8.4m
(Cheah et al, 2015)
Abbreviations:  CR, complete response; m, month; mOS, median overall survival; ORR, objective response rate.
2.3.
CD19 and Expression
CD19 is a 95 kD transmembrane protein expressed only in the B-cell lineage. It is expressed in 
all normal B cells starting at the pre-B-cell stage until the final differentiation stage and is not 
expressed in pluripotent hematopoietic stem cells or most plasma cells.  The pattern of CD19 
expression is maintained in B-cell malignancies, including all subtypes of B-cell NHL, chronic 
lymphocytic leukemia (CLL), and non-T-cell acute lymphoblastic leukemia (Blanc et al, 2011)
with the exception of multiple myeloma.
2.4.
Anti-CD19 CAR T-cell Product
Anti-CD19 chimeric antigen receptor (CAR) T cells are autologous human T cells that have been 
engineered to express an extracellular single-chain variable fragment with specificity for CD19 
linked to an intracellular signaling part comprised of signaling domains from CD28 and CD3ζ 
(CD3-zeta) molecules arranged in tandem. 


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An anti-CD19 CAR vector construct has been designed, optimized, and initially tested at the 
Surgery Branch of the National Cancer Institute (NCI; 09-C-0082; IND 13871) 
(Figure 2)(Kochenderfer et al, 2009; Kochenderfer et al, 2010) is derived from the variable 
region of the anti-CD19 monoclonal antibody FMC63 (Nicholson et al, 1997)CD19 CAR T cells 
(Kowolik et al, 2006)-cell activation.  These fragments were cloned into the murine stem cell 
virus-based vector, utilized to genetically engineer the autologous T cells.  Treatment with anti-
CD19 CAR T cells is currently being administered to subjects with CD19+ B-cell malignancies 
in ongoing NCI protocol (09-C-0082; IND 13871). The same CAR vector construct will be used 
in this study. The same CAR vector construct will be used in this study.
Figure 2.
Anti-CD19 Chimeric Antigen Receptor
Abbreviations:  CAR, chimeric antigen receptor; scFV, single-chain variable region fragment; LTR, long terminal repeat.
2.4.1.
Axicabtagene Ciloleucel
Axicabtagene ciloleucel is manufactured for subjects with lymphomas that are characterized as
not being associated with circulating tumor cells (ie, diffuse large B-cell lymphoma, primary 
mediastinal B-cell lymphoma, and follicular lymphoma).  Briefly, peripheral blood mononuclear 
cells (PBMCs) are obtained by leukapheresis and Ficoll separation.  PBMCs are activated by 
culturing with an anti-CD3 antibody in the presence of recombinant IL-2.  Stimulated cells are 
transduced with a retroviral vector containing an anti-CD19 CAR gene and propagated in culture 
to generate sufficient engineered T cells for administration.  
Patients with r/r MCL may have tumor cells in the peripheral blood, which is associated with a 
poor prognosis (Argatoff et al, 1997).  When the first 10 subjects in Cohort 1 were dosed with 
axicabtagene ciloleucel, it was observed that the incidence and amount of circulating leukemic 
CD28 
S' LTR 
scfv 
CD3( 
3' LTR 
CAR vector construct 
Viral vector 
Target binding domain: 
antibody derived (scFv) 
CAR-engineered 
Tcell 
CAR-engineered 
Tcell 
Tumor cell 


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phase MCL appeared to be higher than rates that are typically for MCL (Argatoff et al, 1997; 
Cheah et al, 2015; Cheah et al, 2016).  Because the axicabtagene ciloleucel manufacturing 
process is not optimized to remove circulating tumor cells from the manufacturing process 
stream, all subsequent patients were dosed using KTE-X19.  
2.4.2.
KTE-X19
KTE-X19 is manufactured for subjects with lymphomas that are characterized by having high 
numbers of CD19-expressing circulating tumor cells (B-cell acute lymphoblastic leukemia, CLL,
and MCL).  Briefly, from the leukapheresis product, the T cells in the harvested leukocytes are 
enriched by binding to magnetic beads coated with anti-CD4 and anti-CD8 antibodies.  T cells
are activated by culturing with anti-CD3 and anti-CD28 antibodies, and are then transduced with 
a retroviral vector containing an anti-CD19 CAR gene. These engineered T cells are then
propagated in culture to generate a sufficient number of cells for administration.  
2.5.
Prior Experience with KTE-X19 and Other Anti-CD19 CAR T Cells
Refer to the current KTE-X19 Investigator’s Brochure (IB) for the most current anti-CD19 CAR 
T cells nonclinical and clinical information.
In regards to ZUMA-2, the interim analysis 2 of Cohort 1 was performed and was reviewed by 
the Data Safety Monitoring Board (DSMB) for safety and futility. The DSMB recommended 
that the study proceed without any changes to the study conduct. Only the safety data from this 
interim analysis are reported in detail below.  As of 31 Dec 2017, 28 subjects have been enrolled, 
treated with conditioning chemotherapy and KTE-X19 (see Table 4).  Four subjects died on 
study: 3 due to progressive disease and 1 due to an adverse event (AE) (organizing pneumonia, 
which was considered related to conditioning chemotherapy but unrelated to KTE-X19).
Table 4.
Subject Disposition, Full Analysis Set
axicabtagene 
ciloleucel
(N=13)
KTE-X19
(N=28)
Cohort 1
(N=43)
Subjects Enrolled n(%)
13 (100)
28 (100)
43 (100)
Subjects Leukapheresed n(%)
13 (100)
28 (100)
43 (100)
Subjects treated with Conditioning Chemotherapy n(%)
11 (85)
28 (100)
40 (93)
Primary reason for ending study for subjects treated with KTE-X19 n(%)
1 (8)
4 (14)
5 (12)
   Death
1 (8)
4 (14)
5 (12)
Note: Percentages are based on number of subjects enrolled.
Data Source: ADSL
Output Source: Table 14.1.2
PROGRAM NAME: t_disp
DATE: 12:13/07FEB2018
Table 5 presents an overall summary of treatment-emergent adverse events (TEAEs) in Cohort 1 
that were reported by 31 DEC 2017. Twenty-seven subjects (96%) in Cohort 1 KTE-X19
subjects experienced TEAE(s) of Grade 3 or higher, including 1 Grade 5 event (organizing 
pneumonia) that is not considered to be KTE-X19-related (see Table 6). The most frequently 
(≥10%) reported incidences of Grade 3 or higher TEAEs by preferred terms are summarized in
Table 7.


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The incidence of cytokine release syndrome (CRS) and neurologic toxicities in the KTE-X19‑
treated subjects in Cohort 1 are also summarized in Table 5. Five subjects (18%) have 
experienced Grade 3 or Grade 4 CRS, and 13 subjects (46%) have experienced Grade 3 or 
Grade 4 neurologic toxicities.  No Grade 5 (death) CRS or neurologic toxicity has been reported.
Table 5.
Overall Summary of AEs, Safety Analysis Set
axicabtagene 
ciloleucel
(N=10)
n (%)
KTE-X19
(N=28)
n (%)
Cohort 1
(N=38)
n (%)
Any TEAE 
10 (100)
28 (100)
38 (100)
  Worst Grade 5
0 (0)
1 (4)
1 (3)
  Worst Grade ≥3
10 (100)
27 (96)
37 (97)
Any Serious TEAE 
8 (80)
22 (79)
30 (79)
  Worst Grade 5
0 (0)
1 (4)
1 (3)
  Worst Grade ≥3
8 (80)
22 (79)
30 (79)
Any TE CRS
10 (100)
27 (96)
37 (97)
  Worst Grade 5
0 (0)
0 (0)
0 (0)
  Worst Grade ≥3
3 (30)
5 (18)
8 (21)
Any TE Neurologic Toxicities infusion
8 (80)
17 (61)
25 (66)
  Worst Grade 5
0 (0)
0 (0)
0 (0)
  Worst Grade ≥3
6 (60)
13 (46)
19 (50)
Abbreviations: TEAE, treatment-emergent adverse event; TE, treatment-emergent.
Note: CRS events were graded by Lee et al 2014. All other events were graded by Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.03.
Treatment-emergent adverse event (TEAE) is an AE with a start date on or after the infusion date of anti-C19 CAR T cells.
Data Source: ADSL, ADAE
Output Source: Table 14.4.1.0
PROGRAM NAME: T_AE_SUMRY
DATE: 12:14/07FEB2018


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Table 6.
Subject Listing of Deaths, Safety Analysis Set
Subject ID
Age/Sex
Leukapheresis
date
Conditioning
Chemotherapy
start date/
end date
KTE-X19
infusion date
Death date/
Study Day
Primary cause
of death
Progressive 
Disease
Progressive 
Disease
Progressive 
Disease
Adverse Event 
(Organizing 
pneumonia)
Data Source: ADSL, ADAE
Output Source: \\sasprod01\stat_prog\KTE-C19\KTE-C19-102\analysis\C1IA3\program\tfl\output\L_16_6_1_DEATH_SAF_C1
PROGRAM NAME: L_DEATH        DATE: 11:28/02MAR2018
Table 7.
Subject Incidence of Frequent (≥ 10%) Grade 3 or Higher Treatment-
emergent Adverse Events by Preferred Terms and Worse Grade, Safety 
Analysis Set (n = 28)
MedDRA Preferred Term n(%)
Any Grade 3 
or Higher
Worst
Grade 3
Worst
Grade 4
Worst
Grade 5
Subjects with any Grade 3 or Higher TE Adverse Event
27 (96)
11 (39)
15 (54)
1 (4)
    Anaemia
15 (54)
15 (54)
0 (0)
0 (0)
    Platelet count decreased
11 (39)
6 (21)
5 (18)
0 (0)
    Neutropenia
10 (36)
7 (25)
3 (11)
0 (0)
    Neutrophil count decreased
9 (32)
4 (14)
5 (18)
0 (0)
    White blood cell count decreased
8 (29)
4 (14)
4 (14)
0 (0)
    Encephalopathy
7 (25)
3 (11)
4 (14)
0 (0)
    Hypertension
5 (18)
5 (18)
0 (0)
0 (0)
    Acute kidney injury
4 (14)
1 (4)
3 (11)
0 (0)
    Confusional state
4 (14)
4 (14)
0 (0)
0 (0)
    Aphasia
3 (11)
3 (11)
0 (0)
0 (0)
    Hypotension
3 (11)
2 (7)
1 (4)
0 (0)
    Hypoxia
3 (11)
1 (4)
2 (7)
0 (0)
    Pneumonia
3 (11)
3 (11)
0 (0)
0 (0)
    Pyrexia
3 (11)
3 (11)
0 (0)
0 (0)
    Respiratory failure
3 (11)
1 (4)
2 (7)
0 (0)
Abbreviations:  MedDRA, Medical Dictionary for Regulatory Activities; TE, treatment-emergent.
Note: Preferred terms are sorted in descending order of total frequency count.
Adverse events are coded using MedDRA Version 19.0 and graded per CTCAE 4.03.
Percentages are calculated using the total number of subjects in the treatment group as the denominator.
Data Source: ADSL, ADAE
Output Source: \\sasprod01\stat_prog\KTE-C19\KTE-C19-
102\analysis\C1IA3\program\tfl\output\T_14_3_8_1_2_G3_TEAE_SAF_XLP
PROGRAM NAME: T_G3_TEAE
DATE: 11:25/02MAR2018
PPD


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2.6.
KTE-X19
Kite Pharma, Inc., (hereafter referred to as Kite) is developing an eACT™ (KTE-X19) that 
targets CD19 expression on B-cell malignancies. The CAR vector construct is identical to the 
one used in the NCI protocol (09-C-0082; IND 13871).  Kite, in conjunction with the NCI 
Surgery Branch, has developed a rapid, closed, and bead-less process for the generation of the 
anti-CD19 CAR T cells.  Closing the process retains the characteristics of the T-cell product 
(Better et al, 2014).  Refer to the current IB for more details.


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3.
STUDY DESIGN
3.1.
General Study Design
Study KTE-C19-102 is a Phase 2, multicenter, open-label study evaluating the safety and 
efficacy of KTE-X19 in subjects with r/r MCL. 
This study is designed to examine the safety and efficacy of KTE-X19 in patients who have r/r 
MCL that has progressed on prior chemotherapy, anti-CD20 antibody, and ibrutinib or 
acalabrutinib.  The study will evaluate the ORR and durability of response after treatment with 
KTE-X19.  An open-label, 2-cohort design is used, with a target ORR in the alternative 
hypothesis of 50% and a futility criterion that the ORR is no more than 25%. Up to 
approximately 130 subjects with r/r MCL in total will be enrolled and treated to evaluate the 
efficacy of KTE-X19.  Cohort 1 will treat up to approximately 90 subjects at a target dose of 
cells/kg, including up to approximately 80 KTE-X19 subjects and 
10 axicabtagene ciloleucel subjects. The Cohort 1 KTE-X19 subjects will form the basis for 
statistical hypothesis testing on the primary endpoint. Cohort 2 will treat up to 40 KTE-X19
subjects at a target dose of 
anti-CD19 CAR T cells/kg.
Each subject will proceed through the following study periods:

Screening 

Enrollment/Leukapheresis 

Bridging therapy, if applicable

Conditioning chemotherapy 

Investigational product (IP) treatment 

Post-treatment assessment 

Long-term follow-up (LTFU)
An independent DSMB will review safety and/or efficacy data 4 times during this study. The 
DSMB will first meet to review safety data when 10 Cohort 1 subjects have been enrolled and 
treated with anti-CD19 CAR T cells and followed for 30 days.  The DSMB will meet for the 
second time to review safety and efficacy data after 20 Cohort 1 subjects have been enrolled and 
treated with anti-CD19 CAR T cells and have had the opportunity to complete the 3-month 
disease assessment.  The DSMB will meet for the third time to review both safety and efficacy 
data after 10 subjects in Cohort 2 have been enrolled and treated with KTE-X19 and have had 
the opportunity to be followed for 30 days. The DSMB will meet for the fourth time to review 
safety data after 44 subjects in Cohort 1 have been enrolled and treated with anti-CD19 CAR 
T cells and have had the opportunity to be followed for at least 30 days, with focus on the safety 
data from the 6 KTE-X19 subjects treated most recently in this cohort. The DSMB will be 
chartered to make trial conduct recommendations based on an analysis of risk vs benefit.  The 
DSMB may meet more often as needed. 
CCI
CCI
-
-


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For details surrounding the DSMB, refer to Section 9.10 and Section 9.11.
For study requirements assigned to each study period, refer to the schedule of assessments 
(SOAs) and Section 7 for details.
A study schema is included in Figure 1.
3.2.
Participating Sites
Approximately 40 centers located in North America and Europe will participate in this study. 
During the conduct of the study, additional regions, countries, or sites may be added as 
necessary.
Sites that do not enroll a subject within 3 months of their site being activated, will be considered 
for closure.
3.3.
Number of Subjects
Participants in this trial will be referred to as “subjects.” It is anticipated that up to 
approximately 130 subjects will be enrolled and treated in this study.
It should be noted that Kite may choose to close enrollment at any time. Refer to Section 10 for 
statistical considerations of the protocol, including sample size estimations.
3.4.
Replacement of Subjects
Subjects will continue to be enrolled until the specified numbers of subjects are attained in the 
modified intent-to-treat (mITT) set.  Subjects who have not received the target dose of 
anti-CD19 CAR T cells will be retained in the analyses of disposition and safety, where 
appropriate (refer to Section 10.5). 
3.5.
Study Duration
3.5.1.
Study Duration for Individual Subjects 
The duration of the study for individual subjects will vary. For a subject who completes the 
entire protocol from the date of informed consent through the completion of the LTFU period,
the duration of the study will take approximately 15 years to complete. However, individual 
study duration will vary depending on a subject’s screening requirements, response to treatment,
and survival. 
The need for prolonged follow-up is based on the potential persistence of gene transfer vectors in 
treated subjects.
3.5.2.
Completion of Study
Completion of the study is defined as the time at which the last subject completes the LTFU
period visit, is considered lost to follow-up, withdraws consent, or dies. 


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4.
SUBJECT SCREENING AND ENROLLMENT
All subjects must sign and date the Independent Review Board/Independent Ethics Committee 
(IRB/IEC) approved consent form before initiating any study-specific procedures or activities 
that are not part of a subject’s routine care. Refer to Section 7 for details.
Each subject who enters the screening period, which starts when the subject signs the informed 
consent form, will receive a unique subject identification (ID) number. This number will be used 
to identify the subject throughout the study and must be used on all study documentation related 
to the subject. The subject identification will never be changed even if the subject is rescreened.
Furthermore, the subject ID number must remain constant throughout the entire clinical study; it 
must not be changed after enrollment or if the subject is rescreened or retreated.


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5.
SUBJECT ELIGIBILITY
5.1.
Inclusion Criteria
101)
Pathologically confirmed MCL, with documentation of either overexpression of cyclin 
D1 or presence of t(11;14)
102)
Up to 5 prior regimens for MCL.  Prior therapy must have included:
Anthracycline or bendamustine-containing chemotherapy, and
Anti-CD20 monoclonal antibody therapy, and
Ibrutinib or acalabrutinib
103)
Relapsed or refractory disease, defined by the following:
Disease progression after last regimen, or
Refractory disease is defined failure to achieve a partial response (PR) or CR to the last 
regimen
104)
At least 1 measurable lesion. Lesions that have been previously irradiated will be 
considered measurable only if progression has been documented following completion of 
radiation therapy
If the only measurable disease is lymph node disease, at least 1 lymph node should be 
≥2 cm
105)
Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous 
system (CNS) lymphoma
106)
At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior
systemic therapy or BTKi (ibrutinib or acalabrutinib) at the time the subject is planned 
for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. 
At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory 
immune checkpoint molecule therapy at the time the subject is planned for leukapheresis 
(eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB 
agonists). 
107)
Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for 
clinically non-significant toxicities such as alopecia)
108)
Age 18 years or older
109)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1


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110)
Absolute neutrophil count (ANC) ≥ 1 000/uL
111)
Platelet count ≥ 75 000/uL
112)
Absolute lymphocyte count ≥ 100/uL
113)
Adequate renal, hepatic, pulmonary, and cardiac function defined as:
Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min 
Serum alanine aminotransferase/aspartate aminotransferase ≤2.5 upper limit of normal 
(ULN)
Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert’s syndrome
Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an 
echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings
No clinical significant pleural effusion
Baseline oxygen saturation > 92% on room air
114)
Females of childbearing potential must have a negative serum or urine pregnancy test.  
Females who have undergone surgical sterilization or who have been postmenopausal for 
at least 2 years are not considered to be of childbearing potential.
5.2.
Exclusion Criteria
201)
History of malignancy other than nonmelanomatous skin cancer or carcinoma in situ 
(eg, cervix, bladder, breast) unless disease-free for at least 3 years 
202)
AutoSCT within 6 weeks of planned KTE-X19 or axicabtagene ciloleucel infusion 
203)
History of allogeneic stem cell transplantation
204)
Prior CD19 targeted therapy with the exception of subjects who received KTE-X19 or 
axicabtagene ciloleucel in this study and are eligible for re-treatment
205)
Prior CAR therapy or other genetically modified T-cell therapy
206)
History of severe, immediate hypersensitivity reaction attributed to aminoglycosides 
207)
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring
intravenous (IV) antimicrobials for management.  Simple urinary tract infection (UTI)
and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
and after consultation with the Kite medical monitor
208)
History of human immunodeficiency virus (HIV) infection or acute or chronic active 
hepatitis B or C infection. Subjects with a history of hepatitis infection must have cleared 
their infection as determined by standard serological and genetic testing.


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209)
Presence of any in-dwelling line or drain (eg, percutaneous nephrostomy tube, 
in-dwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial 
catheter). Ommaya reservoirs and dedicated central venous access catheters, such as a 
Port-a-Cath or Hickman catheter, are permitted.
210)
Subjects with detectable cerebrospinal fluid malignant cells or brain metastases or with a 
history of CNS lymphoma, cerebrospinal fluid malignant cells, or brain metastases
211)
History or presence of CNS disorder, such as seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible 
encephalopathy syndrome, or any autoimmune disease with CNS involvement
212)
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active 
arrhythmias, or other clinically significant cardiac disease within 12 months of 
enrollment
213)
Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
214)
History of symptomatic deep vein thrombosis or pulmonary embolism within the last 6 
months of enrollment  
215)
Possible requirement for urgent therapy due to ongoing or impending oncologic 
emergency (eg, tumor mass effect, tumor lysis syndrome)
216)
Primary immunodeficiency
217)
Any medical condition likely to interfere with assessment of safety or efficacy of study 
treatment
218)
History of severe immediate hypersensitivity reaction to any of the agents used in this 
study 
219)
Live vaccine ≤ 6 weeks prior to planned start of conditioning regimen
220)
Women of childbearing potential who are pregnant or breastfeeding because of the 
potentially dangerous effects of the preparative chemotherapy on the fetus or infant 
221)
Subjects of both genders who are not willing to practice birth control from the time of 
consent through 6 months after the completion of KTE-X19 or axicabtagene ciloleucel
infusion
222)
In the investigator’s judgment, the subject is unlikely to complete all protocol-required 
study visits or procedures, including follow-up visits, or comply with the study 
requirements for participation.
223)
History of autoimmune disease (eg Crohn’s disease, rheumatoid arthritis, systemic lupus) 
resulting in end organ injury or requiring systemic immunosuppression/systemic disease 
modifying agents within the last 2 years


KTE-C 19-102 
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Clinical Protocol 
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6_ 
PROTOCOL TREATMENT 
6.1. 
Treatment Terminology 
The following te1ms will be used to describe and define protocol treatment: 
• 
Bridging therapy, if administered, after discussion with the medical monitor will be 
dexamethasone, ibrntinib, or acalabrntinib. 
• 
The conditioning chemotherapy regimen used for this study will be fludarabine and 
cyclophosphainide. 
• 
The IP for this study is named KTE-X19 and axicabtagene ciloleucel. 
• 
The te1m study treatment refers to all protocol-required therapies. 
6.2. 
6.2.1. 
Study Treatment 
Bridging Therapy 
Bridging therapy will be supplied by the investigative site unless othe1wise noted. Sites should 
refer to the cmTent product label for guidance on packaging, storage, preparation, administration, 
and toxicity management. At the discretion of the investigator and after discussion with the 
medical monitor, bridging therapy may be considered for any subject, particularly those with 
high disease bmden at screening (eg, > 25% manow involvement and/or :::: 1000 leukeinic phase 
mantle cells/mm3 in the peripheral circulation). 
Bridging therapy is to be administered after leukapheresis and must be completed at least 5 days 
prior to initiating conditioning chemotherapy. 
If bridging therapy is administered, the subject must undergo another positron emission 
tomography-computed tomography (PET-CT) to assess disease status prior to receiving 
conditioning chemotherapy and subsequent anti-CD19 CAR T cells infusion. 
6.2.2. 
Conditioning Chemotherapy 
Conditioning chemotherapy will be supplied by the investigative site unless othe1w ise noted. 
Sites should refer to the cunent product label for guidance on packaging, storage, preparation, 
administration, and toxicity management associated with the administration of both agents. 
CONFIDENTIAL 
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Subjects will receive a non-myeloablative conditioning regimen consisting of 
 
 to induce 
lymphocyte depletion and create an optimal environment for expansion of anti-CD19 CAR T 
cells in vivo. Conditioning chemotherapy should only commence when the product is 
available, if required by country regulatory agencies.
6.2.2.1.
Fludarabine 
Fludarabine phosphate (hereafter, fludarabine) is a synthetic purine nucleoside that differs from 
physiologic nucleosides in that the sugar moiety is arabinose instead of ribose or deoxyribose.  
Fludarabine is a purine antagonist antimetabolite.
Refer to the most recent version of the package insert for specific details surrounding the 
administration of fludarabine.
6.2.2.2.
Cyclophosphamide
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent.  Following conversion to 
active metabolites in the liver, cyclophosphamide functions as an alkylating agent; the drug also 
possesses potent immunosuppressive activity.  The serum half-life after IV administration ranges 
from 3 to 12 hours; the drug and/or its metabolites can be detected in the serum for up to 
72 hours after administration.  
Refer to the most recent version of the package insert for specific details surrounding the 
administration of cyclophosphamide.
6.2.2.3.
Mesna
Mesna is a detoxifying agent used to inhibit the hemorrhagic cystitis induced by chemotherapy. 
The active ingredient mesna is a synthetic sulfhydryl compound designated as sodium-2-
mercaptoethane sulfonate with a molecular formula of C2H5NaO3S2. 
Mesna will be administered around the cyclophosphamide dose according to institutional 
standards. Refer to the most recent version of the package insert for specific details surrounding 
the administration of mesna.
6.2.3.
KTE-X19
Refer to the current version of the IB regarding KTE-X19 and related clinical experience.  Refer 
to the Investigational Product Manual for details and instruction on storage and administration of 
KTE-X19.  
KTE-X19 is supplied cryopreserved in cryostorage bags.  The product in the bag is slightly 
cloudy, with cream to yellow color. The cryostorage bags containing KTE-X19 arrive frozen in 
a liquid nitrogen dry shipper.  The bags must be stored in vapor phase of liquid nitrogen, and the 
product remains frozen until the subject is ready for treatment to assure viable live autologous 
cells are administered to the subject. Several inactive ingredients are added to the product to 
assure viability and stability of the live cells through the freezing, thawing, and infusion process.
CCI-


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Final 
KTE-X19 is a subject-specific product, and the intended subject will be identified by a unique 
subject ID number. Upon receipt, verification that the product and subject-specific labels match 
the subject's infonnation (eg, initials, subject ID number) is essential. Do not infuse the product 
if the infonnation on the subject-specific label does not match the intended subject. The volume 
of KTE-X19 infused, the thaw start/stop time, and KTE-X19 administration start/stop time will 
all be noted in the subject medical record. The product must not be thawed until the subject is 
ready for the infusion. Refer to the Investigational Product Manual for details and instruction on 
storage, thawing, and administi·ation of KTE-X19. 
If any problems related to the use of KTE-X19 or any products that suppo1i the management of 
KTE-X19 (eg, cryostorage bags, subject identification labels) required in this study are 
identified, refer to the cmTent Investigational Product Manual for info1mation regarding issue 
repo1iing and resolution. 
6.2.3.1. 
Dose Rationale 
This study is designed to evaluate safe :efficac of two anti-C 
. 
. . 
The recommended ti·eatment re imen for Coho1i I 
is based on the favorable safety:efficacy profile seen in the 
ZUMA-I ti·ial- a Phase 1/2 multicenter study investigating the safety and efficacy of 
axicabtagene ciloleucel in subjects with refracto1y aggressive NHL, which met its primaiy 
endpoint with an ORR of 82% and CR rate of 54% (Locke et al, 2017). 
At the time of the interim analysis 3, 13 subjects (46%) had experienced Grade 3 or Grade 4 
nemologic toxicities (Section 2.5). A phaimacokinetic analysis of KTE-X19 in subjects dosed 
with KTE-X19 in ZUMA-2 Coho1i I (data cutoff: 15 June 2017) demonsu-ated an approximate 
3- to 4-fold higher peak expansion and cumulative exposme (area under curve (AUC)o-2s) 
relative to that seen in subjects ti·eated in ZUMA-I ). Given that CAR T cell peak and AUC0-2s 
are associated with Grade 3 or higher nemologic toxicities in ZUMA-I patients (Neelapu et al, 
2016), the sponsor opted to reduce the KTE-XI 9 target dose to -
anti-CD 19 CAR 
T cells/kg to evaluate safety:efficacy of a lower dose. Therefore, subjects emolled into ZUMA-2 
Coho1i 2 are administered a target dose of-
anti-CD19 CAR T cells/kg, with a 
maximum dose of-
anti-CD19 CAR T cells for subjects ~ 100 kg. 
6.2.4. 
Concomitant Therapy 
Investigators may additionally prescribe any other conc01nitant medications or ti·eatment deemed 
necessaiy to provide adequate suppo1iive cai·e, including growth factor suppo1i ( eg, G-CSF) and 
routine anti-emetic prophylaxis and ti·eatment except those medications listed in the excluded 
medication Section 6.2.5. 
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All concurrent therapies, including medications, intubation, dialysis, oxygen, and blood products, 
should be recorded from the date of the informed consent through 3 months after completing 
treatment with anti-CD19 CAR T cells. After 3 months of follow-up, only targeted concomitant 
medication will be collected for 24 months after anti-CD19 CAR T cells infusion or disease 
progression, whichever occurs first. Targeted concomitant medications include gammaglobulin, 
immunosuppressive drugs, anti-infective drugs, and vaccinations.
For subjects who are enrolled, but not dosed with anti-CD19 CAR T cells, concurrent therapies 
will only be recorded from the date of the informed consent through 30 days after the last study-
specific procedure (eg, leukapheresis, conditioning chemotherapy).  For subjects who are not 
enrolled (eg, screen failure or not leukapheresed), only concurrent therapies related to any 
serious adverse events (SAEs) will be recorded.
Specific concomitant medication collection requirements and instructions are included in the
case report form (CRF) completion guidelines.
6.2.5.
Excluded Medications
Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to 
leukapheresis and 5 days prior to anti-CD19 CAR T cells administration unless used for 
bridging therapy (refer to Section 6.3.2).  
Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months after 
anti-CD19 CAR T cells administration unless used to manage anti-CD19 CAR T cell related 
toxicities (refer to Section 6.4).  Other medications that may interfere with evaluation of the IP, 
such as non-steroidal anti-inflammatory agents, should also be avoided for the same time period 
unless medically necessary. 
Treatment for the subject’s lymphoma, such as chemotherapy, immunotherapy, targeted agents, 
radiation, and high dose corticosteroid, other than defined/allowed in this protocol, and other 
investigational agents are prohibited except as needed for treatment of disease progression after 
anti-CD19 CAR T cells infusion. If permissibility of a specific medication/treatment is in 
question, contact the Kite medical monitor.
6.2.6.
Subsequent Therapy 
Subsequent therapy administered after anti-CD19 CAR T cells infusion for a subject’s disease,
such as non-study specified chemotherapy, immunotherapy, targeted agents, as well as SCT and 
radiation therapy, must be documented until subject completes the LTFU period, is considered 
lost to follow-up, withdraws consent, or dies.   
6.3.
Study Treatment Schedule
6.3.1.
Leukapheresis (Within Approximately 5 Days of Eligibility Confirmation)
Subjects will undergo leukapheresis to obtain leukocytes (white blood cells [WBCs]) for the 
manufacturing of KTE-X19 or axicabtagene ciloleucel.  Leukapheresed cells obtained at 
participating centers will be shipped to the cell processing facility (CPF) overnight as described 
in the Investigational Product Manual.    


KTE-C 19-102 
Clinical Protocol 
Kite Phanna, Inc. 
Final 
Mononuclear cells will be obtained by leukapheresis (12 to 15 liter apheresis with a goal to target 
approximately 5 to 10 x 109 mononuclear cells). The leukapheresed cells are then packaged for 
expedited shipment to the CPF as described in the Investigational Product Manual. 
Upon ~mival at the CPF, each subject's leukapheresed product will be processed to emich for the 
T cell containing PBMC fraction. T cells are then stimulated to expand and transduced with a 
retroviral vector to introduce the CAR gene. The T cells are then expanded and c1yopreserved to 
generate the IP per CPF standard operating procedures (SOPs). After the product has passed 
certain release tests, it will be shipped back to the treating facility. Following completion of each 
subject's conditioning chemotherapy regimen, subjects will receive their respective KTE-X19 or 
axicabtagene ciloleucel infusion. 
6.3.2. 
Bridging Therapy (Administered after Leukapheresis and Completed at 
Least 5 Days Prior to Initiating Conditioning Chemotherapy) 
At the discretion of the investigator and after discussion with the medical monitor, bridging 
therapy may be considered for any subject, pa1t icularly those with high disease burden at 
screening (eg, > 25% maITow involvement and/or~ 1000 leukemic phase mantle cells/mm3 in 
the peripheral circulation). 
Bridging therapy is to be administered after leukapheresis and must be completed at least 5 days 
prior to initiating conditioning chemotherapy. 
If bridging therapy is administered, the patient must undergo another PET-CT to assess disease 
status prior to receiving conditioning chemotherapy and subsequent anti-CD19 CAR T cells 
infusion. 
6.3.3. 
Cyclophosphamide and Fludarabine (Days -5 Through -3 Before Infusion of 
anti-CD19 CART cells) 
Subjects will receive a non-myeloablative conditioning regimen consisting of cyclophosphamide 
and fludarabine to induce lymphocyte depletion and create an optimal environment for expansion 
of anti-CD19 CART cells in vivo. Sub'ects will initiate conditionin chemothera 
with 
cyclophosphainide and fludarabine 
before 
the receiving anti-CD19 CART cells. The 3-day conditioning chemotherapy regimen will be 
administered in an outpatient setting. 
The 3-day conditioning regimen of fludarabine and cyclophosphainide is described below. 
Hydration for cyclophosphamide may alternatively be perfonned according to local institutional 
guidelines. 
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
IV hydration with 1 L of 0.9% NaCl given prior to cyclophosphamide on the day of infusion 
followed by:

Cyclophosphamide 500 mg/m2 IV over approximately 60 minutes followed by:

 


Add mesna per institutional guidelines 
Subjects should be instructed to drink plenty of liquids during and for 24 hours following the 
chemotherapy (approximately 2 liters/24 hours). In general, subjects should be kept well-
hydrated, but closely monitored, to prevent fluid overload. Another balanced crystalloid solution 
(such as Ringer’s lactate) can be used in place of 0.9% NaCl if deemed more appropriate in the 
investigator’s opinion.
6.3.3.1.
Dosing Rationale
Administration of conditioning chemotherapy correlates with clinical responses to adoptive cell 
therapy (Dudley et al, 2008). Specifically, there appears to be a link between adequate 
lymphodepletion and adoptively-transferred T-cell expansion and function.  The depth and 
duration of the lymphodepletion in pre-clinical models correlate with the anti-tumor activity of 
the adoptively-transferred, tumor-specific CD8+ T cells (Gattinoni et al, 2005).  
Lymphodepletion may function by eradicating cytokine sinks for the transferred cells, 
eliminating regulatory T cells, or enhancing the activation of antigen-presenting cells (Klebanoff 
et al, 2005).  Combined treatment with cyclophosphamide and fludarabine represents a potent 
lymphodepleting regimen.  The ZUMA-1 study of axicabtagene cilouleucel in aggressive large 
B-cell lymphoma used the same cyclophosphamide/fludarabine conditioning regimen that is 
being used in the ZUMA-2 study (axicabtagene ciloleucel USPI).  This regimen was tolerated 
prior to infusion of the cellular product and resulted in a favorable risk‑benefit profile.  Similar 
doses of cyclophosphamide and fludarabine have been administered to subjects with B-cell 
malignancies prior to anti-CD19 CAR T cell infusion (NCI Protocol 09‑C‑0082) (Kochenderfer 
et al, 2016) and were shown to increase levels of cytokines known to support T-cell expansion 
and survival (Kochenderfer et al, 2017).  This treatment combination was also used as a reduced 
non-myeloablative conditioning regimen for patients with B-cell malignancies who were 
undergoing alloSCT and resulted in tolerable toxicities (Khouri et al, 1998).
6.3.4.
KTE-X19 or axicabtagene ciloleucel (Day 0, after Fludarabine and 
Cyclophosphamide)
All subjects will be hospitalized to receive treatment with KTE-X19 or axicabtagene ciloleucel
followed by an observation period of at least 7 days unless otherwise required by country 
regulatory agencies (refer to Section 18.3). 
CCI
CCI


KTE-C 19-102 
Clinical Protocol 
Kite Phanna, Inc. 
Final 
The following pre anti-CD19 CAR T cells infusion medications should be administered 
approximately 1 hour prior to infusion. Alternatives to the recommendations below should be 
discussed with the Kite medical monitor. 
• 
Acetaminophen 650 mg PO (500 mg to 1000 mg in EU) 
• 
Diphenhydramine 12.5 mg to 25 mg IV or 25 mg PO 
Subjects in Coho1t 1 will receive anti-CD19 CART cells treatment consisting of a single 
infusion of CAR-transduced autologous T cells administered intravenously at a target dose 
anti-CD19 CART cells/kg. A minimum dose of-
anti-CD19 CART cells/kg may be 
administered for subjects in Coho1t 1. Subjects in Coho1t 2 will receive KTE-X19 treatment 
consisting of a sin le infusion of CAR-transduced autologous T cells administered intravenously 
at a target dose of 
anti-CD19 CART cells/kg. For subjects weighing > 100 kg, a 
maximum flat dose of 
anti-CD19 CAR T cells will be administered for Cohort 1 or-
anti-CD19 CART cells for Coho1t 2. Refer to the Investigational Product Manual for all 
details sunounding the dosing of anti-CD19 CAR T cells. 
Subjects will remain in the hospital through Day 7 after treatment with anti-CD19 CART cells. 
Subjects should not be discharged from the hospital until all anti-CD19 CAR T cells-related 
non-hematological toxicities return to Grade 
1 or return to baseline. Subjects may be 
discharged with non-critical and clinically stable or slowly improving toxicities ( eg, renal 
insufficiency) even if> Grade 1, if deemed appropriate by the investigator. Subjects should 
remain hospitalized for ongoing anti-CD19 CART cells-related fever, hypotension, hypoxia, or 
ongoing central neurological toxicity > Grade 1, or if deemed necessa1y by the treating 
investigator. 
6.4. 
Toxicity Management 
To date, the following impo1tant risks have been identified with KTE-X19 and axicabtagene 
ciloleucel: CRS, neurologic toxicity, infections, and cytopenias. Refer to Section 6 of the 
cmTent 1B for details regarding these events and management guidance. 
As the safety experience with KTE-X19 increases, the management guidance may be updated. 
Therefore, it is impo1tant that you always refer to the most cunent version of the KTE-X19 1B 
for guidance regarding managing KTE-X19 related toxicities. 
Additional infonnation and management recommendations can also be found in the IB regarding 
important potential risks associated with KTE-X19, as well as possible complications associated 
with malignancy and cancer treatment. 
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7.
STUDY PROCEDURES
Research staff should refer to the SOAs (Table 8 and Table 9) for an outline of the procedures 
required. The visit schedule is calculated from anti-CD19 CAR T cells infusion on Day 0. 
An overview of study assessments/procedures is outlined below. A description for each period 
of the study is provided in Section 7.12. Refer to the CRF completion guidelines for data 
collection requirements and documentation of study procedures.
7.1.
Informed Consent
Before a subject’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequate explanation of the study design, 
anticipated benefits, and the potential risks. Subjects should sign the most current IRB/IEC 
approved informed consent form (ICF) prior to any study-specific activity or procedure is 
performed.
The consent process and the subject’s agreement or refusal to participate in the study is to be 
documented in the subject’s medical records. If the subject agrees to participate, the ICF is to be 
signed and personally dated by the subject and by the person who conducted the informed 
consent discussion. The original signed ICF will be retained in accordance with institution 
policy and IRB/IEC requirements with a copy of the ICF provided to the subject.
All subjects who are enrolled into the study should be re-consented with any updated version of 
the IRB/IEC approved ICF if relevant to their participation in the study.
7.2.
Demographic Data
Demographic data will be collected to include sex, age, race, ethnicity, and country of enrollment
to study their possible association with subject safety and treatment effectiveness.
7.3.
Medical and Treatment History
Relevant medical history prior to the start of AE reporting will be collected. Relevant medical 
history is defined as data on the subject’s concurrent medical condition that would be typically 
shared in a referral letter. All findings will be recorded in the CRFs.
In addition to the medical history, all history related to the subject’s disease, treatment, and 
response to treatment will be collected and must date back to the original diagnosis.
For subjects who are being referred from another clinic or institution to the participating research 
center, copies from the subjects chart should be obtained.


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7.4.
Physical Exam, Vital Signs, Performance Status, and European Quality of 
Life-5 Dimensions
Physical exams will be performed during screening and at times noted in the SOA. Changes 
noted in subsequent exams when compared to the baseline exam will be reported as an AE. 
During IP administration/hospitalization, vital signs, including blood pressure, heart rate, oxygen 
saturation, and temperature, will be monitored before and after the anti-CD19 CAR T cells
infusion and then routinely (every 4 to 6 hours) while hospitalized. If the subject has a fever
(temperature 38.3°C or greater) at any time during hospitalization, vital signs will be monitored 
more frequently as clinically indicated.
Performance status as measured by the ECOG scale and will be performed to quantify the 
subject’s general well-being and ability to perform activities of daily life.
The EQ-5D will be completed by the subject, prior to any other assessment, at the screening visit 
and at other times noted in the SOA.  Subjects who are blind or illiterate may have the EQ-5D 
questions read to them by the study staff.  The study staff, however, cannot interpret any of the 
questions for the subject.  A subject may be exempt from completing the questionnaire if he or 
she is unable to read the questionnaire in one of the country languages available.
The EQ-5D is a 2-page generic patient questionnaire for assessing the overall health status of a 
subject.  The EQ-5D consists of a 5-dimension descriptive system, including questions on 
mobility, self-care, usual activities, pain/comfort, and anxiety/depression, and a visual analogue 
scale (VAS) that allows the respondent to record health on a vertical scale (eg, best health to 
worst health), thus allowing a quantitative measure of health outcome.  
7.5.
Neurological Assessment 
Neurological assessments will be standardized by using the Mini-Mental State Examination 
(MMSE) standard version 2.0. The MMSE is a 5 to 10 minute, 11-question measure that 
examines various areas of cognitive function: orientation, attention, immediate recall, short-term 
recall, language, and the ability to follow simple verbal and written commands.
The MMSE is divided into 2 sections.  The first part requires vocal responses to the examiner's 
questions. In the second part of the exam, the subject is asked to follow verbal and written 
instructions, write a sentence spontaneously, and copy a geometric figure. 
A full neurological assessment will be completed during screening to establish a baseline.  For 
subjects enrolled in Cohort 1, subsequent post-baseline assessments will be performed before 
anti-CD19 CAR T cells administration on Day 0, Day 1, Day 3, Day 5, Day 7, and every other 
day while hospitalized, as well as on Day 28 and Month 3.  For subjects enrolled in Cohort 2, a 
subsequent post-baseline assessment will be performed on Day 28. If the assessment shows 
neurologic function has not returned to baseline (± 3 points) on Day 28, then the MMSE will 
continue to be performed at Month 3 and every 3 months until the results have returned to 
baseline (± 3 points) or until Month 24.


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Every attempt should be made to dedicate a single research staff member familiar with or trained 
in the administration of the MMSE to conduct the assessment to minimize inter-rater variability.  
If CNS symptoms persist, continue to perform the MMSE every 2 days until resolution of 
symptoms or discharged from the hospital.
7.6.
Bone Marrow Biopsy
A bone marrow aspirate/biopsy will be performed at screening, if not previously performed
within 4 weeks of signing consent, to assess bone marrow involvement.  The bone marrow
aspirate and biopsy will be assessed and confirmed for the presence of MCL. Subjects with a 
positive bone marrow at screening or those who do not have a baseline bone marrow biopsy 
available, must undergo another bone marrow aspirate and biopsy upon first determination of a 
complete response via PET. Subjects with a negative bone marrow aspirate/biopsy (ie, no MCL)
at screening, and patients with a partial metabolic response, stable disease (SD) or progressive 
disease (PD) at any disease response assessment time point do not require a follow-up bone 
marrow aspirate and biopsy (Figure 3) 
Figure 3.
Bone Marrow Assessment Schema
Abbreviations: BM, bone marrow; ICF, informed consent form; PET-CT, positron emission tomography-computed 
tomography; CR, complete response.
To confirm a CR, the bone marrow aspirate and biopsy must show no evidence of disease by 
morphology or, if indeterminate by morphology, it must be negative by immunohistochemistry.  
After CR is confirmed by bone marrow biopsy, additional bone marrow biopsies are only 
required in case of clinical suspicion of disease progression in the bone marrow only. Refer 
to Section 7.8, Appendix 1 (Section 18.1), and Appendix 2 (Section 18.2) for treatment response 
assessment requirements per the revised International Working Group (IWG) Response Criteria 
for Malignant Lymphoma (Cheson et al, 2007) and Lugano Classification (Cheson et al, 2014).
Not Done 
Must repeat BM biopsy to 
confirm CR irrespective of 
PET-CT findings upon 
response assessment 
Screening BM 
Biopsy 
Done within 1 month before ICF or 
anytime during the Screening period 
Positive for Mantle Cell 
Lymphoma 
Negative for Mantle 
Cell Lymphoma 
No need to repeat BM 
biopsy to confirm CR 


KTE-C 19-102 
Clinical Protocol 
Kite Phanna, Inc. 
Final 
Bone maiTow aspirate/biopsy should also be considered to evaluate hemophagocytic 
lymphohistiocytosis (HLH) as indicated (refer to the cmTent IB). A po1iion of the bone maiTow 
sample collected to evaluate HLH or other toxicities should be submitted to the central 
laborato1y as outlined in the central laborato1y manual. 
7.7. 
Lumbar Puncture 
Subjects with symptoms of central nervous system malignancy, such as new onset severe 
headaches, neck stiffness, or any focal neurologic findings on physical exam, will have lumbar 
puncture perfo1med at the screening visit for examination of cerebral spinal fluid. In addition, 
lumbai· puncture should be perfonned as applicable for subjects with new onset of~ Grade 2 
neurologic toxicities after anti-CD19 CART cells infusion (refer to the cmTent IB). Adequate 
platelet suppo1i should be provided prior to perfo1ming a lumbar puncture ( eg, platelet 
> 50 000/mm3). 
7.8. 
Disease Response Assessment 
Subjects will be evaluated for disease response by the site investigator at times indicated in the 
SOA. For subjects enrolled in Coho1i 1, disease assessments will be evaluated per the revised 
IWG Response Criteria for Malignant Lymphoma as described in Appendix 1 (Section 18.1) 
(Cheson et al, 2007). Flow cytometric, molecular, or cytogenetic studies will not be used to 
dete1mine response. For subjects enrolled in Coho1i 2, disease assessments by the site 
investigator will be evaluated per the Lugano Classification, as described in Appendix 2 
(Section 18.2) (Cheson et al, 2014). 
Baseline PET-CT scans of the neck, chest, abdomen, and pelvis, along with the appropriate 
imaging of all other sites of disease, are required. Subjects will have their first post anti-CD19 
CAR T cells infusion planned PET-CT tumor assessment 4 weeks following the anti-CD19 
CART cells infusion and at regular intervals as highlighted in the SOA during the post-
treatment and LTFU po1iion of the study. 
Post anti-CD19 CART cells administration disease assessments will be used to detennine the 
time when progressive disease occurs. Subjects with symptoms suggestive of disease 
progression should be evaluated for progression at the time symptoms occur even if it is off 
schedule as per the SOA. 
A bone man ow aspirate and biopsy will be perfonned in subjects who are being assessed for CR, 
as described in Appendix 1 (Section 18.1) and Appendix 2 (Section 18.2). Per the revised IWG 
Response Criteria for Malignant Lymphoma (Cheson et al, 2007) and Lugano Classification 
(Cheson et al, 2014), a bone man ow aspirate and biopsy must be perfo1med when the subject 
had bone maiTow involvement with lymphoma prior to therapy or if new abno1malities in the 
peripheral blood counts or blood smear cause clinical suspicion of bone maiTow involvement 
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with lymphoma after treatment.  Furthermore, if bone marrow involvement before the start of the 
study was unknown, a bone marrow evaluation must be conducted to confirm a CR.  The bone 
marrow aspirate and biopsy must show no evidence of disease by morphology or if indeterminate 
by morphology, it must be negative by immunohistochemistry to assign a CR to treatment.  
In addition to the investigator’s assessment, Independent Radiology Review Committee (IRRC)
review per Lugano Classification (Cheson et al, 2014) will be performed for both Cohort 1 and 
Cohort 2. PET-CT scans of all subjects evaluated for disease response will be submitted to and 
reviewed by an independent central reviewer. For subjects who discontinue the study due to an 
assessment of progressive disease, any additional imaging data, subsequent to the image in 
question, will be submitted to the central reviewer to confirm disease status. 
If the subject is eligible for retreatment with KTE-X19, the last scan prior to retreatment will be 
considered the baseline for the purpose of evaluating the response to retreatment.
Requirements for acquisition of PET-CT scans and submission requirements will be outlined in 
the study imaging manual.
7.9.
Cardiac Function 
Each subject’s cardiac function as measured by ECHO will be assessed during the screening 
period to confirm study eligibility. Both left ventricular ejection fraction (LVEF) and pericardial 
effusion will be assessed prior to study entrance by ECHO. An ECHO performed following the 
subject’s last chemotherapy treatment and within 28 days prior to signing the consent may be 
used for confirmation of eligibility.
To establish a baseline, an ECG will also be performed during screening.
7.10.
Magnetic Resonance Imaging
Each subject will undergo a screening brain MRI, with contrast whenever possible or without 
contrast in case of contraindication, to rule out CNS metastasis during the screening period of the 
study. Evaluation of any new onset of ≥ Grade 2 neurologic toxicity should include a brain MRI 
as described in the current IB.
7.11.
Laboratory
The below samples will be collected at the time points indicated in the SOA. Additional samples 
(eg, blood, urine, CSF, tissue) may be collected as needed for further safety testing.

Local lab analysis:
Sodium, potassium, chloride, total bicarbonate, creatinine, glucose, blood urea nitrogen 
or urea (if blood urea nitrogen test cannot be analyzed by the local lab), albumin, calcium 
total magnesium total, inorganic phosphorus, alkaline phosphatase, alanine 
aminotransferase/glutamic-pyruvic transaminase (ALT/GPT), aspartate 
aminotransferase/glutamic-oxaloacetic transaminase (AST/GOT), total bilirubin, 
direct bilirubin, LDH, uric acid 


KTE-C 19-102 
Clinical Protocol 
Kite Phanna, Inc. 
Final 
-
C-reactive protein (CRP) with chemistry panel 
-
Complete blood count (CBC) with differential 
A urine or sernm sample will be collected and assessed locally for females of childbearing 
potential. If the screening pregnancy test is positive, the subjects should not be emolled. If a 
standard of care pregnancy test is collected during the course of the study and the result is 
positive, the investigator should contact the Kite medical monitor for instr11ctions. If a female 
paiiner of a male subject becomes pregnant during the conduct of the study, it must be repo1ied 
by contacting Kite medical monitor for instructions. 
For EU sites, a serology (eg, HIV, hepatitis B, hepatitis C, syphilis) test will be caITied out per 
institutional guidelines and EU regulations. This may be within the 30 days prior to 
leukapheresis and/or on the day of leukapheresis. 
• 
Cent:I'al lab analysis: 
-
Blood draws for PBMC (lymphocyte subsets, replication-competent retr·ovirns [RCR], 
and anti-CD19 CAR T cells) and cytokine analysis will be perfo1med at intervals outlined 
in the SOA. 
-
Sernm samples will also be drawn for anti-CD19 CAR antibodies and human anti-bovine 
antibodies 
For sennn sainples that demonstr·ate increased anti-CD19 CAR antibodies at the 
Month 3 visit over baseline values, attempts should be made to obtain and test 
additional sernm sainples approximately eve1y 3 months until the antibody levels 
retmn to baseline ( or becomes negative) or up to 1 year from the completion of 
tr·eatment, whichever occurs first. 
-
Archived tumor tissue will be collected for centr·al path review and evaluation of 
prognostic mai·kers specific for MCL and pe1iaining to the tumor immune 
environment. Additional analysis may include CD19 ex ression, 
rofilin and anal sis of DNA alterations. 
-
CSF and possibly bone mairnw samples will also be collected and analyzed at the centr·al 
laborato1y as outlined in the schedule of assessments and per Section 7 .11.1. 
-
See centr·al laborato1y manual for details on sample collection, processing, and shipping 
instructions. 
7.11.1. 
Bio markers 
Biomai·ker analysis will be perfonned on blood and tumor samples to evaluate predictive and 
phaim acodynamic markers for anti-CD19 CART cells. Prognostic markers specific for MCL 
and related to the tumor immune environment may also be evaluated in ai·chived and fresh tumor 
biopsies. 
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KTE-C 19-102 
Clinical Protocol 
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Final 
The presence, expansion, persistence, and immunophenotype oftransduced anti-CD19 CAR 
T cells will be monitored in the blood by flow cytomeby. Expansion and persistence will also be 
monitored by a CD19 CAR specific quantitative polymerase chain reaction (qPCR) assay. 
Levels of senun cytokines will also be evaluated in the blood. 
included in the anel: 
Cerebral spinal fluid (CSF), as well as any additional subject samples ( eg, plemal fluid), should 
be collected from subjects who develop a nemologic toxicity or CRS to enable evaluation of 
inflammato1y cytokines and chemokine levels. As applicable, lymphocyte populations residing 
in the CSF or other additional subject samples may also be monitored for the pmpose of 
understanding the safety profile of KTE-X19. 
Because anti-CD19 CAR T cells comprises reti·oviral vector ti·ansduced T cells, the presence of 
RCR in the blood of treated subjects will be monitored. 
In addition, baseline leukapheresis and final anti-CD19 CAR T cells samples will be banked 
and ma 
· 
· 
· 
Archived tmnor tissue will be collected for centi·al pathologic review and evaluation of 
prognostic markers specific for MCL and pe1iaining to the tmnor immune 
environment. Additional analysis ma include CD19 ex ression ene ex ression rofiling, and 
anal sis of somatic DNA alterations. 
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These samples and any other components from these samples may be stored up to 15 years to 
address exploratory research scientific questions related to the treatment or disease under study.  
Each subject will have the right to have the sample material destroyed at any time by contacting 
the investigator who, in turn, can contact the sponsor.  The investigator should provide the 
sponsor the study and subject number so that the sample can be located and destroyed. 
For subjects who withdraw consent, any samples that were not requested to be returned or 
destroyed will remain with the sponsor and any data that may be generated will be entered in the 
study database. 
7.12.
Description of Study Periods
Investigative sites will maintain a log of all screened subjects who were reviewed and evaluated 
for study participation. Information collected on the screening log should include limited 
information, such as the date of screening, date the subject was enrolled, or the reason for why 
the subject failed screening.
7.12.1.
Screening
The screening period begins on the date the subject signs the IRB/IEC approved ICF and 
continues through enrollment. Informed consent must be obtained before completion of any 
study-specific procedures. Procedures that are part of standard of care are not considered study-
specific procedures and may be performed prior to obtaining consent and used to confirm 
eligibility. Confirmation of this data must occur within the time allowance as outlined below and
in the SOA.
After written informed consent has been obtained, subjects will be screened to confirm study 
eligibility and participation. Only subjects who meet the eligibility criteria listed in Section 5
and who commence leukapheresis will be enrolled into the study. If, at any time prior to 
enrollment, the subject fails to meet the eligibility criteria, the subject should be designated as a 
screen failure on the subject screening log with the reasons for failing screening.
The following assessments/procedures are to be completed during the screening period at the 
time points outlined in the SOA:

Medical history

EQ-5D questionnaire (prior to any other assessments/procedures being performed)

Physical examination, including height and weight

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature
Subjects with symptoms of central nervous system malignancy, such as new onset severe 
headaches, neck stiffness, or any focal neurologic findings on physical exam, will have 
lumbar puncture for examination of cerebral spinal fluid.


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Clinical Protocol 
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Final 
• 
ECOG perfo1mance status 
• 
Neurological assessment with MMSE 
• 
ECG 
• 
L VEF (ECHO) and pericardia! effusion assessment (ECHO) 
• 
Imaging studies 
-
Brain MRI 
-
Baseline PET-CT of the neck, chest, abdomen, and pelvis 
PET-CT perfo1med following the subject's last line of therapy and prior to signing 
the consent may be used for confnmation of eligibility 
If PET-CT will be > 28 days at the initiation of conditioning chemotherapy or if the 
subject receives any anti-cancer therapy between screening and conditioning 
chemotherapy (including bridging therapy), the scans must be repeated to establish a 
new baseline. PET CT should be perfo1med as close to emolhnent as possible. 
• 
Bone manow aspirate/biopsy as needed (if not done within 4 weeks prior to screening) 
• 
Labs 
-
~-HCG pregnancy test (sernm or urine) on all women of childbearing potential 
-
Chemistiy panel with CRP 
-
CBC with differential 
• 
SAE repo1iing (refer to Section 9 for safety reporting guidelines) 
• 
Concomitant medications documentation and previous cancer u-eatment histo1y 
• 
7.12.2. 
Rescreening 
Subjects who are unable to complete or meet the eligibility criteria during the 28-day screening 
period will be pe1mitted to rescreen one time. Subjects will retain the same subject ID number 
that was assigned at the original screening. If rescreening occurs within 28 days of the signing of 
the original info1med consent, only the procedure(s)/assessment(s) that did not originally meet 
the eligibility criteria need to be repeated; all other initial screening procedures/assessments do 
not need to be repeated. If rescreening occurs or leukapheresis is delayed more than 28 days 
from the signing of the original infonned consent, subjects must be re-consented and repeat all 
screening procedures/assessments. 
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7.12.3.
Enrollment/Leukapheresis
If any screening assessments or procedures are repeated between confirmation of eligibility and 
the start of leukapheresis and results are outside the eligibility criteria listed in Section 5, contact 
the Kite medical monitor prior to proceeding with leukapheresis.
Before leukapheresis commences, the criteria listed below must be met. If criteria are not met, 
leukapheresis must be delayed until the event resolves. If leukapheresis is delayed beyond 
5 days, baseline CBC with differential and chemistry panel must be repeated. If results are 
outside the eligibility criteria listed in Section 5, contact the Kite medical monitor prior to 
proceeding with leukapheresis. 

No evidence or suspicion of an infection

Corticosteroid therapy at a pharmacologic dose (≥5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 
7 days prior to leukapheresis.
After a subject commences leukapheresis, the subject will be considered enrolled into the study.   
The following procedures/requirements will occur on the leukapheresis collection day and as 
outlined in the SOA:

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Weight

Labs (to be drawn prior to leukapheresis, on the day of or day before leukapheresis)
Chemistry panel
CRP; if CRP is ≥ 100 mg/L, a call must be made to the Kite medical monitor before 
proceeding with conditioning chemotherapy.
CBC with differential
Cytokine levels 
Anti-CD19 CAR antibodies
Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells) 

Leukapheresis

AE/SAE reporting 

Concomitant medications documentation 


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Clinical Protocol
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7.12.4.
Bridging Therapy 
If prescribed, bridging therapy with either a corticosteroid or ibrutinib (or acalabrutinib) must be 
administered after leukapheresis and completed at least 5 days prior to initiating conditioning 
chemotherapy (refer to Section 6.3.2). If bridging therapy is administered, PET-CT scans (and 
bone marrow aspirate/biopsy, if applicable) must be repeated prior to the start of conditioning 
chemotherapy to establish a new baseline. 

AE/SAE reporting 

Concomitant medications documentation 
7.12.5.
Conditioning Chemotherapy Period
If any screening assessments or procedures are repeated between screening and the start of 
conditioning chemotherapy and results are outside the eligibility criteria (Section 5), contact the 
Kite medical monitor for approval prior to proceeding with conditioning chemotherapy.
If PET-CT will be older than 28 days at the initiation of conditioning chemotherapy or if the 
subject receives any anti-cancer therapy with therapeutic intent (eg, radiation, supraphysiologic 
doses of steroids, or chemotherapy) between the last PET-CT and conditioning chemotherapy, 
the diagnostic CT portion of the scan must be repeated to establish a new baseline.
7.12.5.1.
Requirements for Initiating Conditioning Chemotherapy 
Administration of anti-CD19 CAR T cells to subjects with ongoing infection or inflammation, 
even if such processes are asymptomatic, increases the risk of high grade and fatal toxicity.  All 
efforts should be made to rule out such conditions prior to cell infusion. Signs, symptoms or 
abnormal laboratory results attributed to the malignancy (eg “tumor fever,” elevated CRP) are 
diagnoses of exclusion that require a documented workup to establish. Conditioning 
chemotherapy and anti-CD19 CAR T cells infusion should only be initiated after it is 
reasonably assured that cell infusion can safely proceed.
If any of the following criteria are met prior to the initiation of conditioning chemotherapy, then 
the workup listed in Section 7.12.7 must be performed to determine the potential cause if there is 
no identified source of infection.  

Temperature > 38° Celsius within 72 hours of conditioning chemotherapy

CRP > 100 mg/L anytime between enrollment to start of conditioning chemotherapy

WBC count or WBC differential, that is suggestive of infectious process, and is observed
between enrollment and the initiation of conditioning chemotherapy (eg, WBC > 20 000/µL, 
rapidly increasing WBC, or differential with high percentage of segs/bands)


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Additionally:

If any screening assessments or procedures are repeated between confirmation of eligibility
and the start of conditioning chemotherapy and results are outside the eligibility criteria listed 
in Section 5, then the condition must resolve prior to proceeding with conditioning 
chemotherapy.

Complete history and physical exam, including head, ears, eyes, nose, and throat (HEENT) 
exam; cardiac, vascular, respiratory, gastrointestinal, integumentary, and neurological 
systems must not reveal evidence of infection/inflammation.

The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within 48 hours before conditioning chemotherapy (prophylactic use of 
antimicrobials is allowed).  

Treatment course of any antimicrobials given for known or suspected antecedent infection 
should be complete as per infectious disease consult (if applicable) recommendation before 
stopping or switching to prophylactic antimicrobials.  

If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator and in consultation with infectious disease service (if applicable).

The most recently collected blood, urine, or other body fluid cultures must show no growth 
for at least 48 hours, and any other infectious workup performed (eg, bacterial, viral 
serologies, polymerase chain reaction (PCR), stool studies, imaging studies) must be 
negative.  If clinical suspicion is for an infection for which cultures are unlikely to be 
positive within 48 hours (eg, fungal infection), adequate time must be allowed for cultures to 
become positive.
Once the above criteria are met, then the subject can proceed with conditioning chemotherapy.
7.12.5.2.
Conditioning Chemotherapy Administration 
The following procedures will be completed during 
at the time points outlined 
in the SOA:

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Labs (to be drawn prior to chemotherapy)
Chemistry panel with CRP
CBC with differential

Fludarabine and cyclophosphamide administration

AE/SAE reporting 

Concomitant medications documentation 
CCI


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Clinical Protocol
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7.12.6.
Investigational Product Treatment Period
Subjects will be hospitalized to receive treatment with anti-CD19 CAR T cells followed by a
minimum 7-day observation period unless otherwise required by country regulatory agencies 
(refer to Section 18.3). 
7.12.6.1.
Requirements for Initiating KTE-X19 Infusion
If any of the following criteria are met prior to the initiation of KTE-X19 infusion, then the 
workup listed in Section 7.12.7 must be performed to determine the potential cause if there is no 
identified source of infection.  

Temperature > 38° Celsius within 72 hours of KTE-X19 infusion

CRP > 100 mg/L anytime between enrollment to start of  conditioning chemotherapy

WBC count or WBC differential, which is suggestive of infectious process, and is observed
between enrollment and the initiation of KTE-X19 infusion (eg, WBC > 20 000/µL, rapidly 
increasing WBC, or differential with high percentage of segs/bands)
Additionally:

If any screening assessments or procedures are repeated between confirmation of eligibility 
and the start of KTE-X19 infusion and results are outside the eligibility criteria listed in 
Section 5, then the condition must resolve prior to proceeding with KTE-X19 infusion 
(except for peripheral blood cell counts that have been impacted by conditioning 
chemotherapy).

Complete history and physical exam, including HEENT exam, cardiac, vascular, respiratory, 
gastrointestinal, integumentary, and neurological systems, must not reveal evidence of 
infection/inflammation.

The subject must not have received systemic antimicrobials for the treatment of a known or 
suspected infection within 48 hours before KTE-X19 infusion (prophylactic use of 
antimicrobials is allowed).  

Treatment course of any antimicrobials given for known or suspected antecedent infection 
should be complete as per infectious disease consult (if applicable) recommendation before 
stopping or switching to prophylactic antimicrobials.  

If a subject is confirmed to have an infectious process for which antimicrobials are not 
available (eg, viral pneumonia), the infection must be clinically resolved as determined by 
the investigator in consultation with infectious disease service (if applicable).

Most recently collected blood, urine, or other body fluid cultures must show no growth for at 
least 48 hours, and any other infectious workup performed (eg, bacterial, viral serologies, 
PCR, stool studies, imaging studies) must be negative.  If clinical suspicion is for an infection 
for which cultures are unlikely to be positive within 48 hours (eg, fungal infection), adequate 
time must be allowed for cultures to become positive.


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After the above criteria are met, then the subject can proceed with administration of KTE-X19.
If the KTE-X19 infusion is delayed > 2 weeks, protocol guidelines should be followed regarding 
the need for repeat conditioning chemotherapy.
7.12.6.2.
Hospitalization for KTE-X19 Infusion
Subjects will remain in the hospital through Day 7 after treatment with anti-CD19 CAR T cells
unless otherwise required by country regulatory agencies (refer to Section 18.3).  Subjects 
should not be discharged from the hospital until all anti-CD19 CAR T cells-related non-
hematological toxicities return to Grade 1 or return to baseline. Subjects may be discharged with 
non-critical and clinically stable or slowly improving toxicities (eg, renal insufficiency) even if 
> Grade 1 if deemed appropriate by the investigator. Subjects should remain hospitalized for 
ongoing anti-CD19 CAR T cells-related fever, hypotension, hypoxia, or ongoing central 
neurological toxicity > Grade 1 or if deemed necessary by the treating investigator. 
Given the possibility that a subject could develop CRS or a neurologic toxicity in the outpatient 
setting after discharge, subjects and their family members/caregivers should be educated on 
potential symptoms of these syndromes such as fever, dyspnea, confusion, aphasia, dysphasia, 
somnolence, encephalopathy, ataxia, or tremor. If subjects develop these symptoms, they should 
be instructed to immediately contact the principal investigator or seek immediate medical 
attention. 
During this period, the following procedures will be completed at the time points outlined in the 
SOA:

Neurological assessment including MMSE
MMSE will be administered before treatment with anti-CD19 CAR T cells on Day 0, 
then on Day 1, and every other day while hospitalized for subjects enrolled in Cohort 1. 
MMSE will not be administered during the investigational treatment period for subjects 
enrolled in Cohort 2.  

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature, every 
4 to 6 hours during hospitalization

Labs (before anti-CD19 CAR T cells infusion, as described in the SOA)
Chemistry panel with CRP
CBC with differential
Cytokine levels 
Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells, and RCR 
analysis)


KTE-C 19-102 
Clinical Protocol 
Kite Phanna, Inc. 
Final 
• 
illfusion of KTE-X19 or axicabtagene ciloleucel 
• 
• 
• 
AE/SAE repo1iing (refer to Section 9 for safety repo1iing guidelines) 
• 
Concomitant medications documentation 
Monitoring of CRP, fenitin, and LDH (only ifLDH is elevated at baseline) levels may assist 
with the diagnosis and define the clinical course in regards to CRS/neurologic toxicity. It is, 
therefore, recommended that CRP, fenitin, and LDH (if elevated at baseline) be monitored daily 
staiiing at Day O and continuing through hospitalization. ill addition, lactate should be 
monitored as clinically indicated. 
7.12.7. 
Requirements to Work Up Potential Infectious and/or Inflammatory States 
ill the absence of an identified source of infection (eg, line infection, pneumonia on chest x-day), 
the minimum workup to be perfo1med prior to administration of conditioning chemotherapy 
and/or KTE-X19 consists of: 
• 
Call Kite medical monitor 
• 
illfectious Disease service consult (if available) 
• 
CT imaging of the chest, abdomen, and pelvis with IV contrast. If there is a medical 
contraindication to contrast, then non-contrast CT is allowed. 
• 
The following must be perfo1med (prior to the initiation of antimicrobials if clinically 
feasible): 
-
Blood cultures (aerobic and anaerobic x2 bottles each) and UA and urine culture. 
Deep/induced sputum culture if clinically indicated. 
-
All indwelling lines such as central venous catheters should be examined for any signs of 
infection and additional cultures should be drawn from the line 
-
Nasophai-yngeal-throat swab or equivalent assay for viral infection such as influenza A/B 
(including HlNl ), pai·ainfluenza 1/2/3, adenovims, respirato1y syncytial vims, 
coronavims, metapneumovims 
-
Collection of fungal cultures and markers as appropriate ( eg, galactomannan, fungitell) 
-
Collection of appropriate sernm viral studies ( eg, cytomegalovirus [CMV]) 
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
If a central nervous system process is suspected, appropriate brain imaging and subsequent 
lumbar puncture with cytology, culture, Gram stain, and viral PCR should be performed  

Any additional sign or symptom-directed investigation should be performed as clinically 
indicated
Prior to proceeding with conditioning chemotherapy and/or KTE-X19 infusion, the above 
workup must not suggest the presence of an active infection, and all requirements for 
conditioning chemotherapy and/or KTE-X19 infusion must be satisfied. If the KTE-X19
infusion is delayed > 2 weeks following conditioning chemotherapy, protocol guidelines should 
be followed regarding the need for repeat conditioning chemotherapy. 
If the above workup was triggered due to CRP > 100mg/L, CRP should be repeated. If CRP 
continues to increase significantly, an evaluation should be performed for any other potential 
infectious or inflammatory condition that was not previously evaluated. 
7.12.8.
Post-treatment Assessment Period
After completing anti-CD19 CAR T cells infusion and being discharged from the hospital, all 
subjects will be followed in the post-treatment assessment period. Counting from Day 0 (anti-
CD19 CAR T cells infusion), subjects will return to the clinic at the following intervals.

Week 2 (± 2 days)

Week 4 (± 3 days)

Month 2 (± 1 week)

Month 3 (± 1 week)
Subjects will allow key sponsor contacts to continue to access medical records so that 
information related to subjects’ health condition and initial treatment response may be obtained.
The following procedures will be completed for subjects as outlined in the SOA:

EQ-5D questionnaire prior to any other assessments/procedures being performed.

Neurological assessment including MMSE. For subjects enrolled in Cohort 1, the MMSE 
will be performed on Week 4 and Month 3. For subjects enrolled in Cohort 2, the MMSE 
will be performed on Day 28. If the assessment has not returned to baseline (± 3 points) on 
Day 28, then continue to perform the MMSE at Month 3 and every 3 months until the results 
have returned to baseline (± 3 points) or until Month 24.

PET-CT for disease assessment: If the PET-CT is not of high enough resolution, the scan 
must be repeated. Refer to the current version of the imaging site manual for detailed 
instructions.


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Clinical Protocol
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
As applicable, bone marrow aspirate/biopsy to confirm response (ie, for subjects presenting 
with bone marrow involvement prior to therapy or if new abnormalities in the peripheral 
blood counts or blood smear cause clinical suspicion of bone marrow involvement with 
lymphoma after treatment)

Physical exam 

Vital signs, including blood pressure, heart rate, oxygen saturation, and temperature

Labs
β-HCG pregnancy test (serum or urine) on all women of childbearing potential
Chemistry panel with CRP
CBC with differential
Anti-CD19 CAR antibodies
Cytokine levels 
Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells, and RCR 
analysis)

AE/SAE reporting (refer to Section 9 for safety reporting guidelines)

Concomitant medications documentation
If a subject is discharged from the hospital and is subsequently re-admitted to the hospital with 
any anti-CD19 CAR T cells related AEs, the following procedures will be performed as 
outlined in the SOA:

Anti-CD19 CAR T cell levels on day of admission, then weekly, and on day of discharge

Cytokine levels on day of admission, then weekly, and on day of discharge
At any time during the post-treatment assessment period, if a subject did not respond to treatment 
(ie, did not achieve a CR or PR) or progresses following a response and is either not eligible for 
re-treatment or chooses not to pursue re-treatment, the subject will proceed directly to the 
Month 3 visit and be followed for survival, subsequent therapy, and disease outcomes in the 
LTFU period.  A PBMC sample (for anti-CD19 CAR T cells) and serum (for cytokine 
evaluation) should be collected at the time of progression and prior to starting any subsequent 
anti-cancer therapy.
Upon disease progression, sites are encouraged to collect a tumor biopsy and to submit a portion 
of the tumor tissue to the central laboratory for exploratory biomarker analysis.


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Clinical Protocol
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7.12.9.
Long-term Follow-up Period
All enrolled subjects will be followed in the LTFU period for survival and disease status if 
applicable. Subjects will begin the LTFU period after they have completed the Month 3 visit of 
the post-treatment assessment period (whether they have responded to treatment or went straight 
to the Month 3 visit due to disease progression).

Every 3 months (± 2 weeks) through Month 18

Every 6 months (± 1 month) between Month 24 to Month 60

Beginning with Year 6, Month 72 (± 3 months), subjects will return to the clinic 1 time 
annually up to 15 years.  
The following procedures will be completed for subjects who are enrolled and receive anti-
CD19 CAR T cells at the time points outlined in the SOA:

EQ-5D questionnaire (prior to any other assessments/procedures being performed)

For subjects enrolled in Cohort 2, if the MMSE performed on Day 28 and Month 3 has not 
returned to baseline (± 3 points), then continue to perform the MMSE at Month 6 and every 
3 months until the results have returned to baseline (± 3 points) or until Month 24. 

Physical exam

PET-CT scan/disease assessment: through 24 months or until disease progression, whichever 
occurs first.  If subject’s disease has not progressed by Month 24, disease assessments will 
continue to be performed per standard of care.

Survival status

Labs
CBC with differential
Anti-CD19 CAR antibodies (refer to Section 7.11)
Blood draw for PBMCs (includes lymphocyte subsets, anti-CD19 CAR T cells, and RCR 
analysis)

Targeted AE/SAE reporting (for 24 months or until disease progression whichever occurs 
first) (refer to Section 9 for safety reporting guidelines)

Targeted concomitant medication documentation (for 24 months or until disease progression, 
whichever comes first)
Including gammaglobulin, immunosuppressive drugs, anti-infective, and vaccinations 


KTE-C 19-102 
Clinical Protocol 
Kite Phanna, Inc. 
• 
Subsequent therapy for the treatment of lymphoma 
• 
Subjects may also be contacted by telephone to confnm survival status and repo1t targeted 
concomitant medication use. 
Final 
If a subject progresses in the L TFU phase, the subject will continue to be followed for survival 
status and subsequent therapy for the treatment of NHL. A PBMC sample (for anti-CD19 CAR 
T cells) and sennn (for cytokine evaluation) should be collected at the time of progression and 
prior to staiting any subsequent anti-cancer therapy. 
Upon disease progression, sites are encouraged to collect a tumor biopsy and to submit a po1t ion 
of the tumor tissue to the central laborato1y for explorato1y biomarker analysis. 
The following procedures/assessments will be completed for subjects who are emolled, but do 
not receive anti-CD19 CAR T cells, at the time points outlined in the SOA: 
• 
Subsequent therapy 
• 
Smv ival status - subjects may be conta.cted by telephone to confmn smv ival status 
• 
Disease assessment per standard of care: 
• 
AE/SAE repo1t ing and concomitant medication documentation until 30 days after last 
procedure (eg, leukapheresis, conditioning chemotherapy) 
If the subject fails to return to the clinic for a scheduled protocol-specific visit, sites will need to 
make 2 attempts by a combination of telephone and mail to contact the subject. Sites must 
document both attempts to conta.ct the subject. If a subject does not respond within 1 month after 
the second contact, the subject will be considered lost to follow-up, and no additional conta.ct 
will be required. 
Subjects who undergo an alloSCT will be contacted to confnm the sta.tus of their disease and 
smv ival status and will have blood collected for PBMCs per the LTFU schedule. 
7.12.10. 
Retreatment 
Subjects who achieved a PR or CR will have an option to receive a second course of 
conditioning chemotherapy and KTE-X19 under the following conditions: 
• 
Subject had a PR or CR at the Month 3 disease assessment 
• 
Subject's disease subsequently progressed greater than 3 months after axicabtagene 
ciloleucel or KTE-X19 infusion 
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
CD19 tumor expression confirmed locally by biopsy after disease progression and prior to re-
treatment. A portion of the biopsy should be sent to the central laboratory.

Subject continues to meet the original study eligibility criteria with exception of prior 
axicabtagene ciloleucel or KTE-X19 use in this study. Screening assessments should be 
repeated if clinically indicated, as determined by the investigator, to confirm eligibility.

Subject has not received subsequent therapy for the treatment of lymphoma.

Subject did not experience a Grade 4 CRS event per Lee 2014 (except for Grade 4 
hematology laboratory events, including pancytopenia, anemia, neutropenia, neutropenic 
fever, leukopenia, and thrombocytopenia) or Grade 4 neurologic toxicity

Toxicities related to conditioning chemotherapy (fludarabine and cyclophosphamide), with 
the exception of alopecia, have resolved to ≤ Grade 1 or returned to baseline prior to 
re-treatment.

Subject does not have known neutralizing antibodies (exception: if a non-neutralizing 
antibody develops, subjects may be retreated if they meet the original study eligibility 
criteria).
The decision to administer re-treatment should be made in consultation with the Kite medical 
monitor.  In addition, a discussion regarding benefits and risks of retreatment and including the 
need to undergo leukapheresis a second time for the manufacturing of KTE-X19 should occur 
with the subject prior to performing any study-related procedures or treatment. This 
conversation should also be recorded in the subject’s source document.  
A maximum of 1 retreatment course may occur per subject.  Subjects who are retreated must
follow the same treatment schedule and procedural requirements per the initial treatment.
Allowance for retreatment is based on clinical experience reported in the 2 studies conducted at 
the pediatric (Lee et al, 2015) and Surgery Branch (Kochenderfer et al, 2015) of the NCI where 
6 subjects in total have been re-treated upon progression. Three of the re-treated subjects 
(indolent lymphoma/leukemia) experienced durable responses to retreatment after an initial 
response and disease progression.   


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Table 8.
Schedule of Assessments (1 of 2)
Procedures
Screening
Enrollment/
Leukapheresis
Bridging 
Therapy Period
Conditioning Chemotherapy
Period
IP Administration 
Period10
Post-treatment Follow-up
(each visit calculated from Day 0)
Day
Within 
28 days of 
enrollment
Within 
approx. 5 days 
of eligibility 
confirmation
Completed within 
5 days prior to 
Conditioning 
Chemotherapy
-5
-4
-3
-2
-1
0
1 - 7
Week 2
(± 2 days)
Week 4
(± 3 days)
Month 2
(± 1 week)
Month 3
(± 1 week)
Medical history 
X
ECOG Performance Status
X
EQ-5D Questionnaire
X
X
X
Neurological assessment 
including MMSE6for Cohort 1
X
X
QOD
X
X
Neurological assessment 
including MMSE8 for Cohort 2
X
X
X
ECG
X
ECHO
X
Archival/Fresh tumor to central lab 1
X
between Day 7 & Day14
Brain MRI
X
PET-CT/ disease assessment 2
X
X
X
X
Bone Marrow Assessment9
X
X
X
Physical exam
X
X
X
X
X
Vital signs (BP, HR, O2 sat, temp)
X
X
X
X
X
X
X
X
X
X
X
X
Weight (plus height at screening)
X
X
Pregnancy test (serum or urine)
X
X
Lumbar Puncture 3
X
X
Blood draw for Chemistry panel
with CRP
X
X
X
X
X
X
X
X
X
X
X
Blood draw for CBC 
w/differential
X
X
X
X
X
X
X
X
X
X
X
Blood draw for C-reactive 
protein (CRP)
X
X
X
X
X
X
X
X
X
X
X
Blood draw for Anti-CD19 CAR
antibody 4
X
X
X
Blood draw for PBMCs 5, 7
X
X
Day 7
X
X
X
Blood draw for cytokines7
X
X
Day 3 & 7
X
X
Leukapheresis 
X
Bridging Therapy (if applicable)
X


KTE-C 19-102 
Clinical Protocol 
Procedm·es 
Day 
Fludarabine/Cyclophosphamide 
KTE-Xl9 infusion IV 
Adverse events/ 
Concomitant medication 
Sc.reening 
Within 
28 days of 
enl'Ollment 
X 
Enrollment/ 
Leukapheresis 
Within 
approx. 5 days 
of eligibility 
confirmation 
Schedule of Assessments Footnotes 
Bridging 
Therapy Period 
Completed "'ithin 
5 days pt-ior to 
Conditioning 
Chemotherapy 
Kite Pha1ma, Inc. 
Final 
Conditioning Chemotherapy 
IP Administration 
Post-treatment Follow-up 
Period 
Pet-iod1' 
(each visit calculated from Day 0) 
Week2 
Week4 
Month2 
Month 3 
-5 
-4 
-3 
-2 
-1 
0 
1 - 7 
(±2 days) 
(±3 days) 
(± 1 week) 
(± 1 week) 
X 
X 
X 
X 
Abbl'eviations: EQ-5D, Eul'opean Quality ofLife-5 Dimensions; MMSE, Mini-Mental Sta tus Exam; MRI, magnetic l'esonance imaging; BP, blood pl'essul'e; HR, heal't 
l'ate; sat, satul'ation; temp, tempel'atul'e; ECOG, Eastel'n Coope1·ative Oncology Gl'oup; ECG, electl'ocal'diogl'am; ECHO, echocal'diogl'am; PET-CT, positl'on elnission 
tomogl'aphy-computed tomogl'aphy; CAR, chime1ic antigen l'eceptol'; AE, advel'se event; SAE, sel'ious advel'se event; NHL, non-Hodgkin lymphoma; CBC, complete 
blood count; CRP, C-l'eactive pl'otein; PBMC, pel'iphel'al blood mononucleal' cell; IV, intl'avenous; IP, investi ational l'oduct; a 
l'oximate. 
1 
Al·chival tumor sam le: Either FFPE tumor block or u to 20 unstained slides. 
2 
ec -C est-Abdomen-Pelvis)/disease assessment: If PET-CT perfo1med > 28 days prior to the initiation of conditioning chemotherapy, baseline scans must be repeated. 
Screening PET-CT should be completed as close to enrolhuent as possible. A repeat baseline PET-CT is required after bridging therapy and prior to conditioning chemotherapy. 
3 
Lumbar Puncture: Subjects with symptoms of CNS malignancy (eg, new onset severe headaches, neck stiffness, or focal neurological findings) will have lumbar puncttu·e 
pe1fo1med at screening to assess cerebral spinal fluid for possible CNS involvement. Sub' ects with new onset Grade c:: 2 netu·ologic s 
11 toms after KTE-X19 infusion will 
have huuber tmcttu·e erformed to assess cerebral s inal fluid. 
4 
B oo 
aw or Anti-CD19 CAR anti o y: Base me anti o y samp e to 
Anti-CD19 CAR post 3-month samples; 
see Section 7 .11. 
5 
PBMCs: Blood draw for PBMCs include the analysis oflymphocytes, anti KTE-X19 CART cells, and RCR. 
6 
MMSE: Subjects enrolled in Coho1t 1 will have the MMSE assessment at screening, before KTE-X19 administl'ation on Day 0, eve1y other day through hospitalization, 
Day 28, and Month 3. 
7 
If subject is subsequently re-admitted to the hospital with any KTE-X19 related adverse events, blood samples for KTE-X19 CAR T cells and cytokines will be collected on 
day of admission, then weekly, and on day of discharge. Blood samples for anti-CD19 CART cells and cytokines should also be collected at the time of disease progression. 
8 
MMSE: Subjects enrolled in Coho1t 2 will have the MMSE assessments at screening and Day 28. If the assessment has not rettuned to baseline (± 3 points) on Day 28, then 
continue to pe1fo1m the MMSE at Month 3 and eve1y 3 months until the results have retmned to baseline (± 3 points) or until Month 24. 
9 
Bone Mal'l'OW Assessment: Bone ma1l'Ow aspirate/biopsy as needed (if not done within 4 weeks before screening). As applicable, bone ma1l'Ow aspirate/biopsy will be 
pe1fo1med to confom complete response (ie, for subjects presenting with bone ma1Tow involvement prior to therapy or if new abno1malities in the peripheral blood counts or 
blood smear cause clinical suspicion of bone marrow involvement with lymphoma after treatinent). Bone ma1Tow samples may also be collected for subjects who develop 
toxicities after KTE-X19 infusion and will be analyzed centi·ally. See Section 7.11. A repeat bone ma1l'Ow biopsy (if applicable) is required after bridging therapy and prior 
to conditioning chemotherapy. Aftel' CR is confil'med by bone mal'l'OW biopsy, additional bone mal'l'OW biopsies al'e only l'equired in case of clinical suspicion of 
disease pl'ogl'ession in the bone mal'l'OW only. 
10 
Refel' to Section 18.3 fol' l'equil'ements by countl'y l'egulatol'y agencies. 
CONFIDENTIAL 
Page 59 of92 
29 October 2018 


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Kite Pharma, Inc.
Clinical Protocol
Final
CONFIDENTIAL
Page 60 of 92
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Table 9.
Schedule of Assessment (2 of 2)
Procedure
Long-term Follow-up Period 1
(Each visit calculated from Day 0)
Visit Frequency
Month 
6
Month 
9
Month 
12
Month 
15
Month 
18
Month 
24
Month 
30
Month 
36
Month 
42
Month 
48
Month 
54
Month 
60
Month 72 and 
Annually 
Thereafter
EQ-5D Questionnaire
X
Neurological assessment including 
MMSE10for Cohort 2
X
X
X
X
X
X
Physical exam1
X
X
X
X
X
X
PET-CT Disease Assessment2
X
X
X
X
X
X
X2
X2
X2
X2
X2
X2
X2
Bone Marrow Assessment11
X
X
X
X
X
X
Survival Status
X
X
X
X
X
X
X
X
X
X
X
X
X
CBC w/differential 3
X
X
X
X
X
X
Anti-CD19 CAR antibody 4
Blood draw for PBMCs 5
X
X
X
X
X
X
X
X
X
X
Targeted AE/SAEs 6
X
X
X
X
X
X
Targeted concomitant medication 7
X
X
X
X
X
X
X
X
X
X
X
X
X
Subsequent therapy for NHL 8
X
X
X
X
X
X
X
X
X
X
X
X
X
1
Physical exams will continue through the first 24 months.
2
PET Scans/disease assessments will continue through Month 24 or until disease progression, whichever comes first. If subject’s disease has not progressed by Month 24, 
disease assessments will continue to be performed per standard of care.
3
Subjects will continue to provide samples for CBC with differential and lymphocyte subsets through Month 24.
4
Anti-CD19 CAR antibodies post 3-month samples; refer to Section 7.11.
5
Blood draw for PBMCs include the analysis of lymphocytes, anti KTE-X19 CAR T cells, and RCR.
6
Targeted AEs and SAEs will continue for 24 months or until disease progression (whichever occurs first).
7
Targeted concomitant medications will continue for 24 months or until disease progression (whichever occurs first).
8
Subsequent therapy administered after KTE-X19 infusion for a subject’s disease, such as non-study specified chemotherapy, immunotherapy, targeted agents, as well as stem 
cell transplant and radiation therapy, must be collected until subject completes the LTFU period, is considered lost to follow-up, withdraws consent, or dies.  Subjects may be 
contacted by telephone to collect information about subsequent therapy for NHL and to assess survival status.
9
10
MMSE: For subjects enrolled in Cohort 2, if the MMSE performed on Day 28 and Month 3 have not returned to baseline (± 3 points), then continue to perform the MMSE at 
Month 6 and every 3 months until the results have returned to baseline (± 3 points) or until Month 24. 
11
Bone Marrow Assessment: As applicable, bone marrow aspirate/biopsy will be performed to confirm complete response (ie, for subjects presenting with bone 
marrow involvement prior to therapy or if new abnormalities in the peripheral blood counts or blood smear cause clinical suspicion of bone marrow involvement 
with lymphoma after treatment).  After CR is confirmed by bone marrow biopsy, additional bone marrow biopsies are only required in case of clinical suspicion of 
disease progression in the bone marrow only.
CCI
CCI


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Clinical Protocol
Final
CONFIDENTIAL
Page 61 of 92
29 October 2018
8.
SUBJECT WITHDRAWL
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution.
Subjects can decline to continue to receive study required treatment and/or other protocol-
required procedures at any time during the study but continue to participate in the study. This is 
referred to as partial withdrawal of consent.
If partial withdrawal of consent occurs, the investigator must discuss with the subject the 
appropriate process for discontinuation from IP, study treatment, or other protocol-required 
therapies and must discuss options for continued participation, completion of procedures, and the 
associated data collection as outlined in the SOA. The level of follow-up and method of 
communication should also be discussed between the research staff and the subject and
documented in the source documents.
Withdraw of full consent for a study means that the subject does not wish to receive further 
protocol-required therapy or undergo procedures, and the subject does not wish to continue 
further study follow-up. Subject data collected up to withdraw of consent will be retained and
included in the analysis of the study, and, where permitted by local regulations, publically
available data (death records) can be included after withdrawal of consent. The investigator is to 
discuss with the subject appropriate procedures for withdrawal from the study.
As part of the study, sites may be asked to conduct searches of public records, such as those 
establishing survival status, if available, to obtain survival data for any subject for whom the 
survival status is not known. Sites may be also asked to also retrieve autopsy reports to confirm 
status of disease at the time of death. 
The investigator and/or sponsor can also decide to withdraw a subject from the IP and/or other 
protocol-required therapies, protocol procedures, or the study as a whole or at any time prior to 
study completion.
8.1.
Reasons for Removal from Treatment
Reasons for removal from protocol-required investigational products or procedures include any 
of the following:

AE

Subject request

Product not available

Lost to follow-up

Death

Decision by sponsor


KTE-C19-102 
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Clinical Protocol
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CONFIDENTIAL
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8.2.
Reasons for Removal from Study
Reasons for removal of a subject from the study are as follows:

Subject withdrawal of consent from further follow-up

Investigator decision

Lost to follow-up 

Death


KTE-C19-102 
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Clinical Protocol
Final
CONFIDENTIAL
Page 63 of 92
29 October 2018
9.
SAFETY REPORTING
9.1.
AEs
An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does 
not necessarily have a relationship with study treatment. The investigator is responsible for 
ensuring that any AEs observed by the investigator or reported by the subject are recorded in the 
subject’s medical record. 
The definition of AEs includes worsening of a pre-existing medical condition. Worsening 
indicates that the pre-existing medical condition has increased in severity, frequency, and/or 
duration or has an association with a worse outcome. A pre-existing condition that has not 
worsened during the study or involves an intervention, such as elective cosmetic surgery or a 
medical procedure, while on study is not considered an AE.
Interventions for pretreatment conditions (such as elective cosmetic surgery) or medical 
procedures that were planned before study participation are not considered AEs. Hospitalization 
for study treatment infusions or precautionary measures per institutional policy are not 
considered AEs.
The term “disease progression” as assessed by measurement of malignant lesions on radiographs 
or other methods should not be reported as AEs. Death due to disease progression in the absence 
of signs and symptoms should be reported as the primary tumor type (eg, MCL). 
For situations when an AE or SAE is due to the disease under investigation, report the signs and 
symptoms. Worsening of signs and symptoms of the malignancy under study should also be 
reported as AEs in the appropriate section of the CRF. 
The investigator’s clinical judgment is used to determine whether a subject is to be removed 
from treatment due to an AE. If a subject requests to withdraw from protocol-required therapies 
or the study due to an AE, the subject should undergo the procedures outlined in the Month 3 
visit of the SOA. 
9.2.
Reporting of AEs
The investigator is responsible for ensuring that all AEs observed by the investigator or reported 
by the subject that occur from enrollment (ie, commencement of leukapheresis) through 
3 months after treatment with anti-CD19 CAR T cell infusion are monitored and reported.
After 3 months, targeted AEs (eg, neurological, hematological, infections, autoimmune 
disorders, and secondary malignancies) will be monitored and reported for 24 months after 
treatment with anti-CD19 CAR T cells or until disease progression, whichever occurs first.
See Section 9.4 for reporting of non-serious CRS events Grade ≥ 3.


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Clinical Protocol
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For subjects who are enrolled but do not receive anti-CD19 CAR T cells, the AE reporting 
period ends 30 days after the last study-specific procedure (eg, leukapheresis, conditioning 
chemotherapy). 
The investigator must address the below AEs:

AE diagnosis or syndrome (if not known, signs or symptoms)

Dates of onset and resolution

Severity

Assessment of relatedness to IP, conditioning chemotherapy, or study procedures

Action taken
AE grading scale used will be the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 4.03. A copy of the grading scale can be downloaded from the CTEP home 
page (http://ctep.cancer.gov). CRS events will be reported using the Lee grading scale (Lee et al, 
2014), as outlined in the current IB. In reviewing AEs, investigators must assess whether the AE
is possibly related to 1) the IP (axicabtagene ciloleucel or KTE-X19), 2) conditioning 
chemotherapy, or 3) any protocol-required study procedure. The relationship is indicated by a 
yes or no response and entered into the CRF. A yes response should indicate that there is 
evidence to suggest a causal relationship between the study treatment or procedure and the AE.
Additional relevant data with respect to describing the AE will be collected in the CRFs.
The investigator is responsible for reviewing laboratory test results and determining whether an 
abnormal value in an individual study subject represents a clinically significant change from the 
subject’s baseline values. In general, abnormal laboratory findings without clinical significance 
(based on the investigator's judgment) are not to be recorded as AEs. However, abnormal 
laboratory findings that result in new or worsening clinical sequelae, require therapy or 
adjustment in current therapy are considered AEs. Where applicable, clinical sequelae (not the 
laboratory abnormality) are to be recorded as the AE.
The investigator is expected to follow reported AEs until stabilization or resolution. If a subject 
begins a new anti-cancer therapy, the AE reporting period for non-serious AE ends at the time 
the new treatment is started.
9.3.
Definition of SAEs
A SAE is defined as an adverse event that meets at least 1 of the following serious criteria:

Fatal

Life-threatening (places the subject at immediate risk of death)

Requires in-patient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity


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
Congenital anomaly/birth defect

Other medically important serious event
An AE would meet the criterion of “requires hospitalization” if the event necessitated an 
admission to a healthcare facility (eg, overnight stay). 
Events that require an escalation of care when the subject is already hospitalized should be 
recorded as an SAE. Examples of such events include movement from routine care in the 
hospital to the intensive care unit (ICU) or if that event resulted in a prolongation of the existing 
planned hospitalization. 
If an investigator considers an event to be clinically important, but it does not meet any of the 
serious criteria, the event could be classified as an SAE with the criterion of “other medically 
important serious event.” 
The terms “severe” and “serious” are not synonymous.  Severity refers to the intensity of 
an adverse event according to NCI CTCAE criteria; the event itself may be of relatively 
minor medical significance and, therefore, may not meet the seriousness criteria.  Severity 
(ie, grade) and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF.
9.4.
Reporting of SAEs and Non-serious CRS Events Grade ≥ 3
The investigator is responsible for reporting all SAEs observed by the investigator or reported by 
the subject that occur after signing of the consent through 3 months after the anti-CD19 CAR T
cell infusion. After 3 months, only serious targeted AEs (eg, neurological, hematological, 
infections, autoimmune disorders, and secondary malignancies) observed by the investigator or 
reported by the subject will be reported for 24 months after anti-CD19 CAR T cell infusion or 
until disease progression, whichever occurs first.  For subjects who screen fail or are enrolled but 
do not receive anti-CD19 CAR T cells, the reporting period for SAEs ends 30 days after the last 
procedure (eg, screen procedure, leukapheresis, conditioning chemotherapy). 
Serious events that the investigator assesses as related to axicabtagene ciloleucel or KTE-X19
should be reported regardless of the time period.
All SAEs and non-serious CRS events ≥ Grade 3 (Lee et al, 2014) must be submitted via email 
to 
within 24 hours following the investigator’s knowledge of the event
using a SAE Report Form. Subsequently, all SAEs will be reported in accordance with EU 
guidelines, or, if applicable, as per local reporting guidelines. 
Progression of the malignancy during the study should not be reported as an SAE. SAEs 
associated with disease progression may be reported as an SAE. If the malignancy has a fatal 
outcome within 3 months of the last day of the conditioning therapy or anti-CD19 CAR T cell-
infusion, then the event leading to death must be recorded as an SAE with CTCAE Grade 5.
PPD


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Death must be reported if it occurs during the SAE reporting period, irrespective of any 
intervening treatment.
Any death occurring after the first dose of chemotherapy, for the purpose of pre-conditioning, 
and within 3 months of the anti-CD19 CAR T cell infusion, regardless of attribution to 
treatment, requires expedited reporting within 24 hours. Any death occurring greater than 
3 months after the anti-CD19 CAR T cell infusion requires expedited reporting within 24 hours 
only if it is considered related to treatment.
9.5.
Reporting Deaths
Deaths that occur during the protocol-specified adverse event reporting period that are 
attributed by the investigator solely to progression of underlying lymphoma should be 
recorded as SAEs with the preferred term “B-cell lymphoma” and must be reported 
immediately to the sponsor.  Death is an outcome and not a distinct event.  The event or 
condition that caused or contributed to the fatal outcome should be recorded on the AE 
form.  The term “unexplained death” should be captured if the cause of death is not 
known.  However, every effort should be made to capture the established cause of death, 
which may become available later (eg, after autopsy).  Deaths during the post-study 
survival follow-up that are due to underlying cancer should be recorded only on the 
Survival Status CRF.
9.6.
Diagnosis Versus Signs and Symptoms
For adverse events, a diagnosis (if known) rather than individual signs and symptoms 
should be recorded on the AE form.  The exception is for CRS where both the diagnosis 
and signs and symptoms will be captured on the CRF AE form.  For signs and symptoms of 
the underlying cancer, the signs and symptoms should be captured.  However, on the AE 
form, the investigator should state that these signs and symptoms are due to the underlying 
disease.
9.7.
Pregnancy and Lactation
There is no relevant clinical experience with KTE-X19 in pregnant or lactating women, and 
animal reproductive studies have not been performed.  Women of childbearing potential must 
have a negative pregnancy test prior to enrollment because of the potentially dangerous effects of 
the preparative chemotherapy on the fetus.  Women of childbearing potential should be 
monitored according to local and country-specific regulations. This experimental therapy should 
not be administered to pregnant women or women who are breastfeeding.
Female subjects and female partners of male subjects are recommended to use highly effective 
contraception (method must achieve an annual failure rate of < 1%) for at least 6 months after 
conditioning chemotherapy dosing. Male subjects are recommended to not father a child for 
6 months after completion of conditioning chemotherapy dosing.


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If a pregnancy occurs in either a female subject enrolled into the study or a female partner of a 
male subject within 6 months of completing conditioning chemotherapy, the pregnancy must be 
reported to the key sponsor contact.  Information regarding the pregnancy and/or the outcome 
may be requested by the key sponsor. 
In addition to reporting any pregnancies occurring during the study, investigators should monitor 
for pregnancies that occur after the last dose of anti-CD19 CAR T cell infusion through 
6 months for female subjects and for 6 months for the female partner of the male subjects.
The pregnancy should be reported to the key sponsor contact within 24 hours of the 
investigator’s knowledge of the pregnancy event. 
If a lactation case occurs while the female subject is taking protocol-required therapies, report 
the lactation case to the key sponsor contact.
In addition to reporting a lactation case during the study, investigators should monitor for 
lactation cases that occur after the last dose of protocol-required therapies through 6 months.
Any lactation case should be reported to the key sponsor contact within 24 hours of the 
investigator’s knowledge of the event.
9.8.
Hospitalization and Prolonged Hospitalization
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a serious adverse event as described in Section 9.4.  
The following hospitalization scenarios are not considered to be serious adverse events:

Hospitalization for palliative care or hospice care

Planned hospitalization required by the protocol (eg, for monitoring of the subject or to 
perform an efficacy measurement for the study)

Planned hospitalization for a pre-existing condition

Hospitalization due to progression of the underlying cancer
9.9.
Abnormal Vital Signs Values
Not all vital sign abnormalities qualify as an adverse event.  A vital sign result must be 
reported as an adverse event if it is a change from baseline and meets any of the following 
criteria:

Accompanied by clinical symptoms

Results in a medical intervention or a change in concomitant therapy

Clinically significant in the investigator’s judgment


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It is the investigator’s responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality should 
be classified as an adverse event.  However, if a clinically significant vital sign abnormality 
is a sign of a disease or syndrome (eg, high blood pressure), only the diagnosis 
(ie, hypertension) should be recorded on the CRF.
9.10.
Data Safety Monitoring Board
An independent DSMB will review safety and/or efficacy data 4 times during this study. The 
DSMB will first meet to review safety data when 10 subjects in Cohort 1 have been enrolled and 
treated with anti-CD19 CAR T cells and followed for 30 days. The DSMB will meet for the 
second time to review both safety and efficacy data after 20 subjects in Cohort 1 have been 
treated with anti-CD19 CAR T cells and have had the opportunity to complete the 3-month 
disease assessment.  The DSMB will meet for the third time to review both safety and efficacy 
data after 10 subjects in Cohort 2 have been treated with KTE-X19 and have had the opportunity 
to be followed for 30 days. The DSMB will meet for the fourth time after 44 subjects in 
Cohort 1 have been treated with anti‑CD19 CAR T cells and have had opportunity to be 
followed for 30 days after the IP infusion. The DSMB will be chartered to make trial conduct 
recommendations based on an analysis of risk vs benefit.  The DSMB may meet more often as 
needed. 
At the time of expedited reporting of suspected unexpected serious adverse reactions (SUSARs) 
to health authorities, Kite (or designee) will concurrently submit these reports to the DSMB 
chair. The DSMB chair will also review SAE narrative reports monthly.  Finally, the DSMB or 
Kite may request additional analyses of safety data if a safety concern arises during the course of 
the trial.
9.11.
Criteria to Pause Enrollment
As part of its oversight of the study, the DSMB also will assess criteria to pause enrollment after 
10, 20, 30, and 50 subjects in Cohort 1 have been treated with axicabtagene ciloleucel or
KTE-X19 and have had the opportunity to be followed for 30 days.  Enrollment will be paused if 
any of the following criteria is met:

Subject incidence of Grade 5 axicabtagene ciloleucel or KTE-X19 related AEs within 
30 days is > 10%
or

Subject incidence of the following Grade 4 axicabtagene ciloleucel or KTE-X19-related 
AEs lasting more than 7 days is > 33%:
Neurologic toxicity
CRS (per Lee 2014 criteria)
Other non-hematological Grade 4 SAE
Infection (treatment-related)


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10.
STATISTICAL CONSIDERATIONS
10.1.
Hypothesis
This study uses an open-label, 2-cohort design. An alternative hypothesis will be tested among 
Cohort 1 KTE-X19 subjects with a target 50% ORR per independent review against a null 
hypothesis that the ORR is 25% or less. The hypothesis is that the ORR to KTE-X19 in 
Cohort 1 KTE-X19 subjects is significantly greater than 25%. No hypothesis will be tested in 
Cohort 1 axicabtagene ciloleucel subjects and Cohort 2 subjects. 
10.2.
Study Endpoints
10.2.1.
Primary

ORR: Defined as the incidence of a CR or a PR per the Lugano Classification (Cheson et al, 
2014), as determined by the IRRC.  All subjects who do not meet the criteria for an objective 
response by the analysis cutoff date will be considered non-responders, including the subjects 
without any evaluable assessment and those without any assessment.
10.2.2.
Secondary

DOR:  For subjects who experience an objective response, DOR is defined as the time from 
their first objective response to disease progression or death. Subjects not meeting the 
criteria for progression or death by the analysis data cutoff date will be censored at their last 
evaluable disease assessment date and their response will be noted as ongoing  

Best objective response:  the incidence of CR, PR, SD, progressive disease, or unevaluable as 
best response to treatment

ORR (as determined by investigators):  For subjects enrolled in Cohort 1, ORR, as 
determined by study investigators, is defined as the incidence of either a CR or PR per the 
revised IWG Response Criteria for Malignant Lymphoma (Cheson et al, 2007).  For subjects 
enrolled in Cohort 2, ORR, as determined by investigators, is defined as the incidence of 
either a CR or PR per the Lugano Classification (Cheson et al, 2014). All subjects who do 
not meet the criteria for an objective response by the analysis data cutoff date will be 
considered non-responders, including the subjects without any evaluable assessment and 
those without any assessment.

PFS: defined as the time from the anti‑CD19 CAR T-cell infusion date to the date of disease 
progression or death from any cause. Subjects not meeting the criteria for progression by the 
analysis data cutoff date will be censored at their last evaluable disease assessment date.      

OS:  defined as the time from anti‑CD19 CAR T cell infusion to the date of death from any 
cause. Subjects who have not died by the analysis data cutoff date will be censored at the 
last date known alive or the data cutoff date for analysis, whichever is earlier.


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
Incidence of AEs and clinically significant changes in laboratory values

Incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T cells in blood, and 
levels of cytokines in serum

Changes over time in the EQ-5D scale score and EQ-5D VAS score
10.2.3.
Exploratory Endpoints

ORR and duration of second response among subjects retreated with anti‑CD19 CAR T cells
(Section 7.12.10)
10.3.
Sample Size Considerations
This study uses an open-label, 2-cohort design to test for an improvement in ORR. Up to 
approximately 130 subjects with r/r MCL will be enrolled and treated with anti‑CD19 CAR 
T cells, including 10 axicabtagene ciloleucel subjects and up to approximately 80 KTE-X19
subjects in Cohort 1 and up to 40 KTE-X19 subjects in Cohort 2. The primary analysis will be 
conducted after 60 Cohort 1 KTE-X19 subjects have been enrolled and treated and have had the 
opportunity to be evaluated for response 6 months after the Week 4 disease assessment. For the 
test of efficacy, 60 KTE-X19 subjects in Cohort 1 will provide at least 96% power to distinguish 
between an active therapy with a 50% true response rate from a therapy with a response rate of 
25% or less (undesirable response rate, for purposes of futility assessment) with a 1-sided alpha 
level of 0.025.  No hypothesis will be tested in Cohort 1 axicabtagene ciloleucel subjects or
Cohort 2 subjects. Exploratory analyses will be conducted on the data collected from these 
subjects. 
In Cohort 1, 4 interim analyses will be performed:  

Cohort 1 interim analysis 1 will be conducted after 10 subjects in Cohort 1 have been 
enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be
followed for 30 days. This interim analysis will be for safety only.

Cohort 1 interim analysis 2 will be conducted after 20 subjects in Cohort 1 have been 
enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be 
evaluated for response 3 months after treatment with anti‑CD19 CAR T cells.  In this 
interim analysis, the DSMB will review data for both safety and efficacy (futility only).

Cohort 1 interim analysis 3 will occur after 38 subjects in Cohort 1 have been treated with 
anti‑CD19 CAR T cells and have had the opportunity to be assessed for response 6 months 
after the treatment with anti‑CD19 CAR T cells. This interim analysis will be performed 
for a Kite internal review of the accumulating data of safety and efficacy.

Cohort 1 interim analysis 4 will occur after 44 subjects in Cohort 1 have been treated with 
anti‑CD19 CAR T cells and have had the opportunity to be followed for at least 30 days.  In 
this interim analysis, the DSMB will review data for safety only, with focus on the 6 KTE-X19
subjects treated most recently in this cohort.


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In Cohort 2, one interim analysis will be performed:

Cohort 2 interim analysis will be conducted after 10 subjects in Cohort 2 have been enrolled 
and treated with KTE-X19 and have had the opportunity to be followed for 30 days after 
treatment with KTE-X19.  This interim analysis will be for safety and efficacy.
Accrual to the study will continue during all interim analyses.
One primary analysis will be performed:

The primary analysis will be performed with both Cohort 1 and Cohort 2 after 60 KTE-X19
subjects in Cohort 1 have been enrolled and treated and have had the opportunity to be 
assessed for response 6 months after the Week 4 disease assessment.
At the primary analysis, the inferential testing will be performed with data from the Cohort 1
KTE-X19 subjects only, using a 1-sided alpha level of 0.025. This procedure preserves the 
designated overall alpha level (1-sided) of 0.025 and has at least 96% power when 60 KTE-X19
subjects are included.  EAST version 6.4 were used for power calculation and evaluation of the 
operating characteristics of this design.
For Cohort 1, a rho (parameter = 0.30) beta spending function will be used to allocate the beta 
level between the futility analysis and the primary efficacy analysis.  
10.4.
Statistical Assumptions
As described in Section 3, an open-label, 2-cohort design is used. A target response rate of 50% 
and a historical control rate of 25% are assumed for statistical inference. The responses from 
subjects in the study population are assumed to be independent and follow binomial distribution,
and, thus, the exact binomial test will be used to test the statistical hypothesis.
10.5.
Analysis Subsets 

mITT set:  will consist of all subjects enrolled and treated with anti‑CD19 CAR T cells at 
any dose.  This analysis set will be used for analyses of the efficacy endpoints (objective 
response rate, best objective response, DOR, PFS, OS) for the study.

Inferential analysis set: will consist of the first 60 treated KTE-X19 subjects in 
Cohort 1. This analysis set will be used for the hypothesis testing of the primary 
endpoint ORR at the time of the primary analysis, as well as the analyses on the key 
secondary endpoints (best objective response [BOR], DOR, PFS, and OS).

Safety analysis set:  defined as all subjects treated with any dose of anti‑CD19 CAR T cells.
This analysis set will be used for all analysis of safety.

Full analysis set (FAS):  will consist of all enrolled subjects and will be used for the 
summary of subject disposition, sensitivity analyses of ORR and key secondary endpoints,
and subject listings of deaths.


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10.6.
Access to Individual Subject Treatment Assignments
This is an open-label, 2-cohort study, and subjects and investigators will be aware of treatment 
received. Data handling procedures for the study will be devised to reduce potential sources of 
bias and maintain the validity and credibility of the study. These procedures will be outlined in 
the study Statistical Analysis Plan, DSMB charter, and Trial Integrity Document.
10.7.
Interim Analysis
10.7.1.
Interim Analysis and Early Stopping Rules
An independent DSMB will be formed to review accumulating safety data after 10 subjects in 
Cohort 1 have been enrolled and treated with anti‑CD19 CAR T cells and have had the 
opportunity to be followed for 30 days for safety. The DSMB will review accumulating safety 
and efficacy data after 20 subjects in Cohort 1 have been treated with anti‑CD19 CAR T cells
and have had the opportunity to complete the 3-month disease assessment after the treatment 
with anti‑CD19 CAR T cells. The DSMB will also review safety and efficacy after 10 subjects 
in Cohort 2 have been treated with KTE-X19 and have had opportunity to be followed for 
30 days after the KTE-X19 infusion. The DSMB will review safety again after 44 subjects in 
Cohort 1 have been enrolled and treated with anti‑CD19 CAR T cells and have had the 
opportunity to be followed for 30 days after the treatment with anti‑CD19 CAR T cells, with 
focus on the safety data from the 6 KTE-X19 subjects treated most recently within this cohort.
The DSMB will also monitor safety criteria to pause enrollment (see Section 9.11).
10.7.2.
Safety Interim Analysis  
The DSMB will review the safety data only twice, after 10 and 44 subjects in Cohort 1 have been 
enrolled and treated with anti‑CD19 CAR T cells and have had the opportunity to be followed 
for 30 days for safety, respectively. The DSMB will also review SAE information and SUSARs 
on a regular basis throughout subject treatment in the study. The DSMB may request additional 
safety data or modifying the study conduct. The sponsor may request additional reviews by the 
DSMB if safety concerns are identified. Data submitted to the DSMB may be monitored or 
unmonitored to facilitate and ensure timely DSMB review.  
10.7.3.
Efficacy Interim Analysis
In Cohort 1, two efficacy interim analyses will be performed.  
Interim analysis 2 (Efficacy analysis 1) will be conducted after 20 subjects have been treated 
with anti‑CD19 CAR T cells and have had the opportunity to be followed for 3 months after the 
treatment with anti‑CD19 CAR T cells.  This interim analysis will be for futility only.  If more 
than 5 responses are observed in the first 20 subjects, accrual in Cohort 1 will continue. 


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Interim analysis 3 (Efficacy analysis 2) will be conducted after 38 subjects in Cohort 1 have been 
treated with anti‑CD19 CAR T cells and have had the opportunity to be assessed for response 
6 months after the treatment with anti‑CD19 CAR T cells. This interim analysis will be 
performed for a Kite internal review of the accumulating data of safety and efficacy.
A rho (parameter = 0.30) beta spending function will be used to allocate the beta level between 
this futility analysis and the primary efficacy analysis in Cohort 1.    
In Cohort 2, one interim analysis will be conducted after 10 KTE-X19 subjects have been 
enrolled and have had the opportunity to be followed for 30 days after treatment with KTE-X19. 
This interim analysis will be for safety and efficacy.  
10.7.4.
Other Interim Analysis
The sponsor reserves the right to conduct additional analyses of safety and efficacy during the 
time between the planned interim analyses and primary analysis for regulatory interaction 
purposes. If conducted, no formal hypothesis testing will be performed in such analyses.
10.8.
Planned Methods of Analysis
The primary analysis will be performed after 60 KTE-X19 subjects in Cohort 1 have been 
treated and have had the opportunity to be evaluated for response 6 months after the Week 4 
disease assessment. In this primary analysis, inferential testing of efficacy will be performed 
with data from Cohort 1 KTE-X19 subjects only, and the analysis with the data from Cohort 1 
axicabtagene ciloleucel subjects and Cohort 2 will be descriptive. Additional analyses may 
occur after the primary analysis has been completed.  These additional analyses will be 
descriptive and will occur after inferential testing in Cohort 1 has been performed.  The final 
analysis will occur when all subjects in both cohorts have completed the study.  
The primary endpoint of ORR will be based on IRRC review of disease assessments in the mITT 
set.  Analyses of ORR based on investigator review of disease assessments will also be 
performed.
10.8.1.
ORR
The incidence of objective response and exact 2-sided 95% confidence intervals will be 
generated for Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, and 
Cohort 2 subjects.  An exact binomial test will be used to compare the observed ORR per IRRC 
review in Cohort 1 KTE-X19 subjects to a response rate of 25%.
10.8.2.
Best Objective Response
The incidence of subjects with CR, PR, SD, progressive disease, and unevaluable as best 
response to treatment and exact 2-sided 95% confidence intervals about the incidence will be 
generated for Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, and 
Cohort 2 subjects.


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10.8.3.
DOR
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for DOR for 
Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, and Cohort 2 subjects.
DOR will be derived using disease assessments obtained on study prior to initiation of new anti-
cancer therapy (including SCT).  The DOR for subjects who undergo SCT while in remission
will be censored at the last evaluable assessment date prior to SCT; a sensitivity analysis will be 
conducted in which disease assessments obtained after SCT are included in the derivation of 
DOR. 
10.8.4.
PFS
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for PFS time for 
Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, and Cohort 2 subjects.
Estimates of the proportion of subjects alive and progression-free at 3-month intervals will be 
provided.
10.8.5.
OS
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS for 
Cohort 1 KTE-X19 subjects, Cohort 1 axicabtagene ciloleucel subjects, and Cohort 2 subjects.
Estimates of the proportion of subjects alive at 3-month intervals will be provided.
10.8.6.
Safety
Subject incidence rates of AEs, including all, serious, fatal, CTCAE version 4.03 Grade 3 or
higher, and TEAEs with onsets on or after the date of KTE-X19 or axicabtagene ciloleucel
infusion, will be tabulated by preferred terms and system organ class. Changes in laboratory 
values and vital signs will be summarized with descriptive statistics. The incidence of 
concomitant medications will be summarized.
Tables and/or narratives of deaths through the LTFU and treatment related SAEs will be 
provided.
10.8.7.
Long-term Data Analysis
All subjects will be followed for survival for up to approximately 15 years after the last subject 
receives his or her last KTE-X19 or axicabtagene ciloleucel infusion. No formal hypothesis 
testing will be performed based on data obtained after the primary analysis. Descriptive 
estimates of key efficacy and safety analyses may be updated to assess the overall treatment 
profile.


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11.
REGULATORY OBLIGATIONS 
11.1.
Independent Review Board/Independent Ethics Committee 
A copy of the protocol, ICF, and any additional subject or trial information, such as subject 
recruitment materials, must be submitted to each site’s respective IRB/IEC for approval. After
approval is obtained from the IRB/IEC, all documents must be provided to the key sponsor 
contact before subject recruitment can begin.
The investigator must also receive IRB/IEC approval for all protocol and ICF changes or 
amendments. Investigators must ensure that ongoing/continuous IRB/IEC approval (ie, annual 
approval) is provided throughout the conduct of the study. Copies of IRB/IEC approval are to be 
forwarded to the key sponsor contact for archiving.
During the course of the study, investigators are to submit site-specific and study SAEs 
(provided to the site by the key sponsor contact), along with any protocol deviations, to their 
IRB/IEC in accordance with their respective IRB/IEC policies. 
11.2.
Subject Confidentiality
Subject confidentiality must be maintained for all material submitted to the key sponsor contact. 
The following rules are to be applied.

Subjects will be identified by a unique ID number.

Date of birth or year of birth/age at time of enrollment will be reported according with local 
laws and regulations.
For reporting of SAEs, subjects will be identified by their respective subject ID number, initials,
and date of birth or year of birth (as per their local reporting requirements for both initials and 
date of birth).
Per federal regulations and International Conference on Harmonisation/Good Clinical Practice
(ICH/GCP) guidelines, investigators and institutions are required to permit authorization to the 
sponsor, Contract Research Organization (CRO), IRB/IEC, and regulatory agencies to subject’s
original source documents for verification of study data. The investigator is responsible for 
informing potential subjects that such individuals will have access to their medical records,
which includes personal information.
11.3.
Investigator Signatory Obligations
Each clinical study report will be signed by the coordinating investigator. The coordinating 
investigator will be identified by Kite under the following criteria:

A recognized expert in the disease setting

Provided significant contributions to the design or analysis of study data

Participated in the study and enrolled a high number of eligible subjects


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12.
PROTOCOL AMENDMENTS AND TERMINATION
If the protocol is amended, the Investigator’s Agreement with the amendment and the IRB/IEC 
approval of the amendment must be obtained. Documentation acknowledging approval from 
both parties is to be submitted to the key sponsor contact.
Both Kite and the investigator reserve the right to terminate the investigator’s participation in the 
study as per the terms of the agreement in the study contract. The investigator is to provide 
written communication to the IRB/IEC of the trial completion or early termination and provide 
the CRO with a copy of the correspondence.
Kite reserves the unilateral right, at is sole discretion, to determine whether to manufacture CAR
T cells and provide them to sites and subjects after the completion of the study and before 
treatment becomes commercially available.


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13.
STUDY DOCUMENTATION AND ARCHIVE
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated. These individuals authorized to fulfil these responsibilities should be outlined and 
included in the Delegation of Authority Form.
Source documents are original documents, data, and records for which the study data are 
collected and verified. Example of such source documents may include, but are not limited to,
hospital records and patient charts; laboratory, pharmacy, radiology, and records; subject diaries;
microfiches; correspondence; and death registries. CRF entries may be considered as source data 
if the site of the original data collection is not available. However, use of the CRFs as source 
documentation as a routine practice is not recommended.
The investigator and study staff are responsible for maintaining a comprehensive and centralized
filing system of all subject records that are readily retrieved to be monitored and/or audited at 
any time by the key sponsor contact, regulatory authorities, and IRB/IECs. The filing system 
will include at minimum:

Subject content including ICFs and subject ID lists

Protocols and protocol amendments, IB, copies of pre-study documentation, and all IRB/IEC 
and sponsor communication

Proof of receipt, experimental treatment flow records, and experimental product-related 
correspondence.
Original source documents supporting entries into CRFs must be maintained at the site and 
readily available upon request. No study documents should be discarded without prior written 
agreement between Kite and the investigator. Should storage no longer be available to archive 
source documents or must be moved to an alternative location, the research staff should notify 
the key sponsor contact prior to the shipping the documents.


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14.
STUDY MONITORING AND DATA COLLECTION
The key sponsor contact, monitors, auditors, or regulatory inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and verifying 
source documents and records assuring that subject confidentially is respected.
The monitor is responsible for source document verification of CRF data at regular intervals 
during the study. Protocol adherence, accuracy, and consistency of study conduct and data 
collection with respect to local regulations will be confirmed. Monitors will have access to 
subject records as identified in Section 13.
By signing the Investigator’s Agreement, the investigator agrees to cooperate with the monitor to 
address and resolve issues identified during monitoring visits.
In accordance with ICH/GCP and the audit plan, a site may be chosen for a site audit. A site 
audit would include, but is not limited to, an inspection of the facility(ies), review of subject and 
study-related records, and compliance with protocol requirements as well as ICH/GCP and 
applicable regulatory policies.
All data will be collected in an electronic CRF system. All entries must be completed in English,
and concomitant medications should be identified by tradenames. For further details 
surrounding the completion of CRFs, refer to the CRF completion guidelines.


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15.
PUBLICATION
Authorship of publications from data generated in study KTE-C19-102 will be determined based 
on the uniform requirements for manuscripts submitted to biomedical journals (as outlined in the 
International Committee of Medical Journal Editors December 2013) which states: 

Authorship should be based on:
Substantial contributions to the conception or design of the work, acquisition of data,
analysis, or interpretation of data for the work; and
Drafting the article or revising it critically for important intellectual content; and
Final approval of the version to be published; and
Agreement to be accountable for all aspects of the work in ensuring that questions related 
to the accuracy or integrity of any part of the work re appropriately investigated or 
resolved
When a large, multicenter group has conducted the work, the group should identify the 
individuals who accept direct responsibility for the manuscript. This individual should fully 
meet the criteria for authorship defined above.
Funding, collection of data, or general supervision of the research alone or in combination does 
not qualify an individual for authorship.
Any publication, in any form, that is derived from this study must be submitted to Kite for
review and approval. The study contract among the institution, principal investigator, and Kite
or its delegate will outline the requirements for publication review.


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16.
COMPENSATION
Kite will provide compensation for study-related illness or injury pursuant to the information 
outlined in the injury section of the ICF.


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Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother. 
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Meeting Abstracts. 2016;34(15_suppl):LBA3010.
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18.
APPENDIX
18.1.
Appendix 1:  Revised IWG Response Criteria for Malignant Lymphoma
Information in this section has been taken from (Cheson et al, 2007).
18.1.1.
Complete Response
Complete response (CR) requires all of the following: 

Complete disappearance of all detectable clinical evidence of disease and disease-related 
symptoms if present before therapy. 

Typically fluorodeoxyglucose (FDG)-avid lymphoma (large cell, mantle cell, and follicular 
lymphomas are all typically FDG-avid):  In subjects with no pre-treatment positron emission 
tomography (PET) scan or when the PET scan was positive before therapy, a post-treatment 
residual mass of any size is permitted as long as it is PET negative.  

Variably FDG-avid lymphomas/FDG avidity unknown:  In subjects without a pre-treatment 
PET scan or if a pre-treatment PET scan was negative, all lymph nodes and nodal masses 
must have regressed to normal size (≤ 1.5 cm in greatest diameter if > 1.5 cm before 
therapy).  Previously involved nodes that were 1.1 to 1.5 cm in their long axis and more than 
1 cm in their short axis before treatment must have decreased to ≤ 1.0 cm in their short axis 
after treatment.  

The spleen and/or liver, if considered to be enlarged before therapy on basis of physical exam 
or CT scan, must should be normal size on CT scan and not be palpable on physical 
examination, and nodules thought to represent lymphoma must no longer be present.  

A bone marrow aspirate and biopsy is performed only when the patient had bone marrow 
involvement with lymphoma prior to therapy or if new abnormalities in the peripheral blood 
counts or blood smear cause clinical suspicion of bone marrow involvement with lymphoma 
after treatment.  The bone marrow aspirate and biopsy must show no evidence of disease by 
morphology, or, if indeterminate by morphology, it must be negative by 
immunohistochemistry.  The biopsy core sample must be a minimum of 20 mm in length. 
18.1.2.
Partial Response
A partial response (PR) requires all of the following:

≥50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest 
dominant nodes or nodal masses.  Dominant nodes or nodal masses should be clearly 
measurable in at least 2 perpendicular dimensions, should be from different regions of the 
body if possible, and should include mediastinal and retroperitoneal nodes if possible.  

No increase in size of nodes, liver, or spleen and no new sites of disease.  


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
If multiple splenic and hepatic nodules are present, they must regress by ≥ 50% in the SPD.  
There must be a > 50% decrease in the greatest transverse diameter for single nodules.   

Bone marrow is irrelevant for determination of a PR.  If subject has persistent bone marrow 
involvement and otherwise meets criteria for CR, then the subject will be considered a PR.

Typically FDG-avid lymphoma:  for subjects with no pre-treatment PET scan or if the PET 
scan was positive before therapy, the post-treatment PET scan should be positive in at least 
1 previously involved site.  Note: in subjects with follicular lymphoma or mantle cell 
lymphoma, a PET scan is only indicated in subjects with 1 or at most 2 residual masses that 
have regressed by 50% on CT scan.
18.1.3.
Stable Disease
Stable disease (SD) requires:

Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for 
progressive disease.  PET should be positive in typically FDG-avid lymphomas.
18.1.4.
Progressive Disease
Progressive disease (PD) is defined by at least one of the following:  

≥ 50% increase from nadir in the sum of the products of at least 2 lymph nodes, or, if a single 
node is involved, at least a 50% increase in the product of the diameters of this 1 node  

Appearance of a new lesion > 1.5 cm in any axis even if other lesions are decreasing in size

≥50% increase in size of splenic or hepatic nodules 

At least a 50% increase in the longest diameter of any single previously identified node more 
than 1 cm in its short axis

Lesions should be PET positive in typically FDG-avid lymphomas unless the lesion is too 
small to be detected by PET (< 1.5 cm in its long axis by CT).


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18.2.
Appendix 2:  Lugano Classification
Refer to imaging manual and (Cheson et al, 2014) for details of assessment.
Table 10.
5-point Scale (5PS)
Score
Description
1
No uptake above background
2
Uptake ≤mediastinum
3
Uptake > mediastinum but ≤liver
4
Uptake moderately higher than liver
5
Uptake markedly higher than liver and/or new lesions
X
New areas of uptake unlikely to be related to lymphoma
From (Barrington et al, 2014)
18.2.1.
Complete Response
18.2.1.1.
Complete Metabolic Response
The designation of complete metabolic response (CMR) for PET-CT-based response requires all 
of the following:

A 5-point scale (5PS) score of 1, 2, or 3, with or without a residual mass
In Waldeyer’s ring or extranodal sites with high physiologic uptake or with activation 
within spleen or marrow, uptake may be greater than normal mediastinum and/or liver.
In this circumstance, CMR may be inferred if uptake at sites of initial involvement is no 
greater than surrounding normal tissue even if the tissue has high physiologic uptake.

No new sites of disease should be observed.
18.2.2.
Complete Radiologic Response 
The designation of complete radiologic response (CRR) for CT-based response requires all of the 
following:

Target nodes/nodal masses must regress to ≤ 1.5 cm in longest transverse diameter of a lesion 
(LDi).

No extralymphatic sites of disease

Absent non-measured lesion

Organ enlargement regress to normal (eg, an enlarged spleen at baseline must be ≤13 cm at 
assessment)


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
No new sites of disease should be observed.

Bone marrow normal by morphology; if indeterminate, immunohistochemistry negative 
18.2.3.
Partial Response
18.2.3.1.
Partial Metabolic Response
The designation of partial metabolic response (PMR) for PET-CT-based response requires all of 
the following:

A 5PS score of 4 or 5, with reduced uptake compared to baseline (screening), and residual 
mass(es) of any size

Note:
At interim, these findings suggest responding disease.
At end of treatment, these findings suggest residual disease.

No new sites of disease should be observed.
If there are persistent focal changes in the marrow in the context of a nodal response, 
consideration should be given to further evaluation with magnetic resonance imaging or biopsy 
or an interval scan.
18.2.3.2.
Partial Radiologic Response
The designation of partial radiologic response (PRR) for CT-based response requires all of the 
following:

≥50% decrease in the SPD of up to 6 target measurable nodes and extra-nodal sites
When a lesion is too small to measure by CT, assign 5 mm x 5 mm as the default value.
For a node > 5 mm x 5 mm, but smaller than normal, use actual measurements for 
calculation.

Absent/normal, regressed, but no increase of non-measured lesions

Spleen must have regressed by > 50% in length beyond normal (ie, ≤13 cm).  For example, 
if the spleen is 15 cm at baseline, it must be ≤14 cm at assessment to classify as a PRR. 


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18.2.4.
Stable Disease
18.2.4.1.
No Metabolic Response
The designation of no metabolic response (NMR) for PET-CT-based response requires all of the 
following:

A 5PS score of 4 or 5, with no significant change in FDG uptake compared to baseline 
(screening), at an interim time point or end of treatment

No new sites of disease should be observed.
18.2.4.1.1.
Stable Radiologic Disease
The designation of stable radiologic disease (SRD) for CT-based response requires all of the 
following:

< 50% decrease from baseline in the SPD of up to 6 dominant, measurable nodes and extra-
nodal sites; no criteria for progressive disease (PD) are met

No increase consistent with progression in non-measured lesion and organ enlargement

No new sites of disease should be observed.
18.2.4.2.
PD
18.2.4.2.1.
Progressive Metabolic Disease
The designation of progressive metabolic disease (PMD) for PET-CT-based response requires at 
least 1 of the following:

A 5PS score 4 or 5 with an increase in intensity of uptake from baseline, and/or

New FDG-avid foci consistent with lymphoma at interim or end of treatment assessment

New FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, 
inflammation). If uncertain regarding etiology of new lesions, biopsy or interval scan may be 
considered.

New or recurrent FDG-avid foci in bone marrow.
18.2.4.3.
Progressive Radiologic Disease
The designation of progressive radiologic disease (PRD) for CT-based response requires at least 
1 of the following:


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
An individual node/lesion must be abnormal with:
LDi > 1.5 cm, and
Increase by ≥ 50% from cross-product of LDi and perpendicular diameter (PPD) nadir,
and
An increase in LDi or shortest axis perpendicular to the LDi fromnadir
■
0.5 cm for lesions ≤ 2 cm
■
1.0 cm for lesions > 2 cm
In the setting of splenomegaly, the splenic length must increase by > 50% of the extent of 
its prior increase beyond baseline (eg, a 15 cm spleen must increase to > 16 cm). If no 
prior splenomegaly, the increase must be ≥2 cm from baseline;
New or recurrent splenomegaly

New or clear progression of pre-existing non-measured lesions

New lesion
Regrowth of previously resolved lesions
A new node > 1.5 cm in any axis
A new extra-nodal site > 1.0 cm in any axis; if < 1.0 cm in any axis, its presence must be 
unequivocal and must be attributable to lymphoma
Assessable disease of any size unequivocally attributable tolymphoma

New or recurrent bone marrow involvement


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18.3.
Appendix 3: Monitoring of Subjects After IP Administration per Country 
Regulatory Agencies
Germany:
The post-infusion monitoring of subjects, described in Section 7.12.6.2 in this protocol, will 
be extended by monitoring on Day 8, Day 9, and Day 10, according to procedures outlined 
in Table 8, column “IP administration period, 1-7.” The subject may stay hospitalized or 
return to the clinic daily for this extended monitoring at the discretion of the investigator. 
The daily monitoring will include vital signs (see Section 7.4), blood draw for chemistry 
panel with C-reactive protein (CRP), blood draw for complete blood count (CBC) with 
differential (see Section 7.11), and neurological assessment, including Mini-Mental Status 
Exam (MMSE) (see section 7.5). Any observed toxicity will be managed according to 
Section 6.4 of this protocol.

SAP_001.pdf: 
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Product Name:
KTE-X19
Protocol:
A Phase 2 Multicenter Study Evaluating the Efficacy of 
KTE-X19 in Subjects with Relapsed/Refractory Mantle Cell 
Lymphoma (ZUMA-2)
Version Number:
Version 6.0
Release Date:
08 July 2019
Replaces Previous Version(s):
Version 5.0; dated 22 October 2018
CONFIDENTIALITY NOTICE
This document contains confidential information of Kite Pharma Inc., a wholly owned subsidiary 
of Gilead Sciences Inc. This document must not be disclosed to anyone other than the site 
research staff and members of the Institutional Review Board/Independent Ethics Committee, a 
scientific review board or an equivalent. The information in this document cannot be used for 
any purpose other than the conduct of the clinical investigation without the prior written consent 
of Kite Pharma Inc. Questions regarding how this document should be used or the conduct of 
the clinical trial should be directed to the key sponsor contacts.


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF TABLES.........................................................................................................................................................4
LIST OF ABBREVIATIONS........................................................................................................................................5
1.
INTRODUCTION ................................................................................................................................................6
2.
OBJECTIVES.......................................................................................................................................................7
3.
STUDY OVERVIEW...........................................................................................................................................8
3.1.
Study Design............................................................................................................................................8
3.2.
Hypothesis................................................................................................................................................9
3.3.
Sample Size Considerations.....................................................................................................................9
3.4.
Statistical Assumptions ..........................................................................................................................11
4.
STUDY ENDPOINTS AND COVARIATES ....................................................................................................12
4.1.
Endpoints ...............................................................................................................................................12
4.1.1.
Primary.................................................................................................................................12
4.1.2.
Secondary.............................................................................................................................12
4.1.3.
Exploratory...........................................................................................................................12
4.2.
Covariates...............................................................................................................................................13
4.2.1.
Baseline Covariates..............................................................................................................13
4.2.2.
Tocilizumab and Steroid use after Anti-CD19 CAR T Cells Infusion .................................14
5.
DEFINITIONS....................................................................................................................................................15
5.1.
General...................................................................................................................................................15
5.2.
Safety .....................................................................................................................................................16
5.3.
Efficacy..................................................................................................................................................17
6.
ANALYSIS SETS...............................................................................................................................................19
6.1.
Modified Intent-to-treat..........................................................................................................................19
6.2.
Inferential Analysis Set..........................................................................................................................19
6.3.
Safety Analysis Set ................................................................................................................................19
6.4.
Full Analysis Set ....................................................................................................................................19
6.5.
mITT Retreatment Analysis Set.............................................................................................................19
6.6.
Safety Retreatment Analysis Set............................................................................................................19
6.7.
Subgroup Analysis Sets..........................................................................................................................19
7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES...................................................................20
7.1.
Interim Analysis.....................................................................................................................................20
7.2.
Assessment of Criteria to Pause Enrollment ..........................................................................................20
7.3.
Access to Aggregate and Subject-level Data and Individual Subject Treatment Assignments..............21
8.
DATA SCREENING AND ACCEPTANCE......................................................................................................22
8.1.
General Principles ..................................................................................................................................22
8.2.
Electronic Transfer and Archival of Data ..............................................................................................22
8.3.
Handling of Missing and Incomplete Data.............................................................................................22
8.3.1.
Efficacy ................................................................................................................................22
8.3.2.
Safety....................................................................................................................................22
8.4.
Detection of Bias....................................................................................................................................23
8.5.
Outliers...................................................................................................................................................23
8.6.
Distributional Characteristics.................................................................................................................23


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8.7.
Validation and Configuration Management ...........................................................................................23
9.
STATISTICAL METHODS OF ANALYSIS ....................................................................................................24
9.1.
General Principles ..................................................................................................................................24
9.2.
Subject Accountability...........................................................................................................................24
9.3.
Important Protocol Deviations ...............................................................................................................24
9.4.
Demographic and Baseline Characteristics............................................................................................24
9.5.
Efficacy Analyses...................................................................................................................................25
9.5.1.
ORR and Best Response.......................................................................................................26
9.5.2.
DOR .....................................................................................................................................27
9.5.3.
PFS.......................................................................................................................................27
9.5.4.
OS.........................................................................................................................................27
9.5.5.
Tumor Burden ......................................................................................................................28
9.5.6.
Objective Response and Best Response Among Subjects Retreated with 
Anti-CD19 CAR T Cells......................................................................................................28
9.5.7.
DORR...................................................................................................................................28
9.5.8.
Incidence of SCT..................................................................................................................28
9.5.9.
European Quality of Life-5 Dimensions and Visual Analogue Scale 
Scores...................................................................................................................................28
9.6.
Safety Analyses......................................................................................................................................28
9.6.1.
AEs.......................................................................................................................................29
9.6.2.
Procedures and Concomitant Medications ...........................................................................30
9.6.3.
Laboratory Test Results........................................................................................................30
9.6.4.
Anti-CD19 CAR Antibodies ................................................................................................30
9.6.5.
RCR......................................................................................................................................30
9.6.6.
Exposure to Study Treatment...............................................................................................30
9.6.7.
Exposure to Concomitant Medications and Procedures .......................................................31
9.6.8.
Mini-mental Status Exam.....................................................................................................31
9.7.
Subsequent Anti-cancer Therapy ...........................................................................................................31
9.8.
Schedule of Study Treatment .................................................................................................................31
9.9.
CAR T Cells Measured in Peripheral Blood..........................................................................................32
9.10.
B-cell Aplasia.........................................................................................................................................32
10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES.............................................................................33
11.
REFERENCES ...................................................................................................................................................34
12.
HISTORY OF REVISIONS ...............................................................................................................................35
13.
APPENDICES ....................................................................................................................................................37
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates...........37
Appendix 2.
Sample Adverse Event Table Layouts....................................................................................39
Appendix 3.
Derivation of Time to Event Endpoints and Last Date Known to Be Alive...........................40
Appendix 4.
Derivation of Simplified Mantle Cell Lymphoma International Prognostic Index ................44


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LIST OF TABLES
Table 1.
Imputation Rules for Partial or Missing Start Dates...............................................................37
Table 2.
Subject Incidence of <AE Descriptor> AEs by Preferred Term (Worst Grade).....................39
Table 3.
Subject Incidence of <AE Descriptor> AEs by System Organ Class and Preferred 
Term (Worst Grade) ...............................................................................................................39
Table 4.
Primary Analysis of DOR ......................................................................................................40
Table 5.
Sensitivity Analysis of DOR (to include data after SCT post study treatment)......................41
Table 6.
Primary Analysis of PFS ........................................................................................................42
Table 7.
Sensitivity Analysis of PFS....................................................................................................42
Table 8.
Analysis of OS........................................................................................................................43
Table 9.
Simplified Mantle Cell Lymphoma International Prognostic Index.......................................44
Table 10.
Risk Category Based on s-MIPI.............................................................................................44


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LIST OF ABBREVIATIONS 
ADaM
Analysis data model
AE
Adverse event
Allo-SCT
Allogeneic stem cell transplant
Auto-SCT
Autologous stem cell transplant
CAR
Chimeric antigen receptor
CIF
Cumulative incidence 
CR
Complete response
CRS
Cytokine release syndrome
CTCAE
Common Terminology Criteria for Adverse Event
DOR
Duration of response
DORR
Duration of response to retreatment
DSMB
Data Safety Monitoring Board
ECOG
Eastern Cooperative Oncology Group
EQ-5D
European quality of life-5 dimensions
FAS
Full analysis set
HLGT
High-level group term
IRRC
Independent Radiology Review Committee
MCL
Mantle cell lymphoma 
mITT
Modified intent-to-treat
MedDRA
Medical Dictionary for Regulatory Activities
NE
Not evaluable
OS
Overall survival
PD
Progressive disease
PFS
Progression-free survival
PR
Partial response
RCR
Replication-competent retrovirus
r/r MCL
Relapsed/refractory mantle cell lymphoma
SAE
Serious adverse event
SCT
Stem cell transplant
SD
Stable disease
SDTM
Study data tabulation model 
SMQ
Standardized MedDRA query 
s-MIPI
Simplified Mantle Cell Lymphoma International Prognostic Index 
SOC
System organ class
SPD
Sum of the product of the diameter
TEAE
Treatment-emergent adverse event
TLS
Tumor lysis syndrome
VAS
Visual analogue scale


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1.
INTRODUCTION
This statistical analysis plan provides the pre-specification and details for the statistical analyses 
outlined within protocol KTE-C19-102 entitled “A Phase 2 Multicenter Study Evaluating the 
Efficacy of KTE-X19 in Subjects with Relapsed/Refractory Mantle Cell Lymphoma
(ZUMA-2).”  The scope of this document is to provide details on the planned interim, primary, 
and final analyses.


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2.
OBJECTIVES
The primary objective is to evaluate the efficacy of KTE-X19, as measured by objective 
response rate (ORR), in subjects with relapsed/refractory (r/r) mantle cell lymphoma (MCL).  
Secondary objectives include assessing the safety and tolerability of KTE-X19, additional 
efficacy endpoints, and the change in the European Quality of Life-5 Dimensions (EQ-5D) 
scores from baseline to Month 6. 


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3.
STUDY OVERVIEW
3.1.
Study Design
Study KTE-C19-102 is a multicenter, open-label Phase 2 study evaluating the safety and efficacy 
of KTE-X19 in subjects with r/r MCL.  
Up to approximately 130 subjects with r/r MCL in total will be enrolled and treated in 2 cohorts. 
Cohort 1 will treat up to approximately 90 subjects at a target dose of 2 x 106 anti-CD19 CAR 
T cells/kg, including at least 60 but up to approximately 80 subjects treated with KTE-X19
(According to original treatment not retreatment; referred to as KTE-X19 subjects in this 
document) and 10 subjects treated with axicabtagene ciloleucel (According to original treatment 
not retreatment; referred to as axicabtagene ciloleucel subjects in this document). The Cohort 1 
KTE-X19 subjects will form the basis for statistical hypothesis testing on the primary endpoint. 
Cohort 2 will treat up to approximately 40 KTE-X19 subjects at a target dose of 0.5 x 106 anti-
CD19 CAR T cells/kg. Details regarding KTE-X19 and axicabtagene ciloleucel products can be 
found in the protocol. Throughout this document, KTE-X19/axicabtagene ciloleucel may be 
referred to as anti-CD19 CAR T cells.
Each subject will proceed through the following study periods:

Screening

Enrollment/Leukapheresis

Bridging therapy, if applicable

Conditioning chemotherapy 

Investigational product treatment 

Post-treatment assessment

Long-term follow-up
Additional details on study procedures may be found in the study protocol.  
An independent Data Safety Monitoring Board (DSMB) will meet and review safety and/or 
efficacy data 4 times during the study:
For Cohort 1: The DSMB will first meet to review safety data when 10 subjects have been 
treated with anti-CD19 CAR T cells and have been followed for 30 days. The DSMB will meet 
for the second time to review both safety and efficacy data after 20 subjects have been treated 
with anti-CD19 CAR T cells and have had the opportunity to complete the 3-month disease 
assessment. The DSMB will review safety again after 44 subjects in Cohort 1 have been treated 


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with anti-CD19 CAR T cells and have had opportunity to be followed for at least 30 days after 
the anti-CD19 CAR T cells infusion, with focus on the safety data from the 6 KTE-X19 subjects 
treated most recently within this cohort.
For Cohort 2: The DSMB will meet to review both safety and efficacy data after 10 subjects 
have been treated with KTE-X19 and have had the opportunity to be followed for 30 days.
The DSMB will be chartered to make trial conduct recommendations based on an analysis of risk 
vs benefit. The DSMB may meet more often as needed. 
There will be an additional interim analysis for Cohort 1 after 38 subjects treated with anti-CD19 
CAR T cells in Cohort 1 have had the opportunity to be evaluated for response 6 months after the 
anti-CD19 CAR T cells infusion. This interim analysis will be performed for a Kite Pharma, 
Inc., (hereafter referred to as Kite or Kite Pharma) internal review of the accumulating data of 
safety and efficacy. 
The primary analysis will occur after 60 KTE-X19 subjects have been enrolled and treated in 
Cohort 1 and have had the opportunity to be evaluated for response 6 months after the Week 4 
disease assessment (see details in Section 3.3).
The primary analysis of efficacy endpoints will be based on the Lugano Classification {Cheson 
2007} per Independent Radiology Review Committee (IRRC) review. These assessments will 
be referred to as “Central Read” in this document. Secondary efficacy analyses will be based on 
investigator review of disease assessments, henceforth referred to as “Investigator Read.” For 
Cohort 1, the Investigator Read will be based on the revised International Working Group 
Criteria for Malignant Lymphoma {Cheson 2007}; for Cohort 2, the Investigator Read will be 
based on the Lugano Classification {Cheson 2014}.   
3.2.
Hypothesis
This study is designed to differentiate between a treatment that has a true ORR of 50% (target 
response rate) per IRRC review and a treatment with a true ORR of 25% or less.  The hypothesis 
is that the ORR to KTE-X19 per IRRC review is significantly greater than 25%.  This hypothesis 
will be tested on Cohort 1 inferential analysis set. No hypothesis will be tested in the Cohort 1 
axicabtagene ciloleucel subjects or Cohort 2 subjects – Analysis conducted on the data collected 
from these subjects will be descriptive.
3.3.
Sample Size Considerations
This study uses an open-label 2-cohort design to test for an improvement in ORR. Up to 
approximately 130 subjects with r/r MCL will be enrolled and treated with anti-CD19 CAR T 
cells, including 10 axicabtagene ciloleucel subjects and up to approximately 80 KTE-X19
subjects in Cohort 1 and up to approximately 40 KTE-X19 subjects in Cohort 2. Hypothesis 
testing of the primary endpoint ORR will be conducted on Cohort 1 inferential analysis set. 
Primary analysis will be conducted after 60 KTE-X19 subjects have been enrolled and treated 
and have had the opportunity to be assessed for response 6 months after the Week 4 disease 


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assessment. A sample size of 60 KTE-X19 subjects in Cohort 1 provides at least 96% power to 
distinguish between an active therapy with a 50% true response rate from a therapy with a 
response rate of 25% or less, with a 1-sided alpha level of 0.025. 
Four interim analyses in Cohort 1 and one interim analysis in Cohort 2 will be performed:

Cohort 1 interim analysis 1 will be conducted after 10 subjects have been treated with 
anti-CD19 CAR T cells and have been followed for 30 days. In this interim analysis, the 
DSMB will review data for safety only.

Cohort 1 interim analysis 2 will be conducted after 20 subjects have had the opportunity to be 
evaluated for response 3 months after treatment with anti-CD19 CAR T cells. In this interim 
analysis, the DSMB will review data for both safety and efficacy (futility only).

Cohort 1 interim analysis 3 will occur after all the 38 treated subjects in this cohort have had 
the opportunity to be evaluated for response 6 months after anti-CD19 CAR T cells infusion.
This interim analysis will be performed for a Kite internal review of the accumulating data of 
safety and efficacy.

Cohort 1 interim analysis 4 will occur after 44 subjects in Cohort 1 have been treated with 
anti-CD19 CAR T cells and have had the opportunity to be followed for 30 days after 
anti-CD19 CAR T cells infusion.  In this interim analysis, the DSMB will review data for 
safety only, with focus on the 6 KTE-X19 subjects treated most recently in this cohort.

Cohort 2 interim analysis will occur after 10 subjects in this cohort have been enrolled and 
treated with KTE-X19 and have had the opportunity to be followed for 30 days after 
KTE-X19 infusion.  This interim analysis will be for safety and efficacy.
Accrual to and treatment on the study will continue during all interim analyses. The primary 
analysis will occur after 60 KTE-X19 subjects have been enrolled and treated in Cohort 1 and 
have had the opportunity to be evaluated for response 6 months after the Week 4 disease 
assessment. Data from both Cohort 1 and Cohort 2 will be analyzed. However, as mentioned 
above, no statistical hypothesis will be formally tested on Cohort 1 axicabtagene ciloleucel
subjects and Cohort 2  subjects, and, thus, no alpha-spending is assigned for the analysis of 
Cohort 1 axicabtagene ciloleucel subjects and Cohort 2 subjects. The primary analysis on
Cohort 1 will use a 1-sided alpha level of 0.025, with one interim efficacy analysis for futility.
This procedure preserves the designated overall alpha level (1-sided) of 0.025 and achieves at 
least 96% power.
For Cohort 1, a rho (parameter = 0.30) beta spending function will be used to allocate the beta 
level between the futility analysis and the primary efficacy analysis. The non-binding futility 
boundary for this interim analysis is reached if no more than 5 responders (≤5) out of 20 subjects 
are observed. EAST version 6.4 was used to evaluate the statistical power and operating 
characteristics of this design. 


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3.4.
Statistical Assumptions
As described in Section 3.3, an open-label 2-cohort design is used for this study. In the Cohort 1 
KTE-X19 subjects, a target ORR of 50% and a historical control rate of 25% are assumed for 
statistical inference. The responses from subjects in the study population are assumed to be 
independent and follow binomial distribution, and, thus, an exact binomial test will be used to 
test the statistical hypothesis.


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4.
STUDY ENDPOINTS AND COVARIATES
4.1.
Endpoints
4.1.1.
Primary

ORR, defined as the incidence of complete response (CR) or partial response (PR) per the 
Lugano Classification {Cheson 2014} as determined by the IRRC review
4.1.2.
Secondary

Duration of response (DOR)

Best objective response

ORR per investigator review

Progression-free survival (PFS)

Overall survival (OS)

Incidence of adverse events (AEs) and clinically significant changes in laboratory values

Incidence of anti-CD19 CAR antibodies

Levels of anti-CD19 CAR+ T cells in blood

Levels of cytokines in serum

Changes over time in the European quality of life-5 dimensions (EQ-5D) scale score and 
EQ-5D visual analogue scale (VAS) score
4.1.3.
Exploratory
CCI


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4.2.
Covariates
4.2.1.
Baseline Covariates
The following baseline covariates may be used to examine efficacy and/or safety in subgroups or 
covariate analyses:

Eastern Cooperative Oncology Group (ECOG) performance status at baseline

Age (in years) at baseline (< 65, ≥ 65)

Sex (male, female)

Race:  white, Asian, American Indian or Alaska Native, Black or African American, Native 
Hawaiian or Other Pacific Islander, other (categories may be collapsed or expanded based on 
accrual)

Relapsed/Refractory subgroup (relapsed after autologous stem cell transplant [auto-SCT], 
relapsed after last mantle cell lymphoma [MCL] chemotherapy, refractory to last MCL 
chemotherapy)

Morphologic characteristics (blastoid, pleomorphic, diffuse, mantle zone, nodular)

Ki-67 index (%)

t(11; 14) (Y/N)

Cyclin D1 overexpression (Y/N)

Disease stage (I, II, III, IV) and extent (presence of B symptoms, S [splenic involvement], 
E [extranodal disease], X [bulky disease], bone marrow involvement) as determined by the 
investigator at screening

Simplified Mantle Cell Lymphoma International Prognostic Index (s-MIPI)

Number of prior regimens

Prior Burton tyrosine kinase inhibitors (ibrutinib vs acalabrutinib)
CCI


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
Prior therapy regimens (anti-CD20 [Y/N], anthracycline [Y/N], bendamustine [Y/N], 
ibrutinib [Y/N], acalabrutinib [Y/N], lenalidomide [Y/N], bortezomib [Y/N], temsirolimus 
[Y/N], stem cell transplant [Y/N], platinum [Y/N])

Tumor burden, as measured by the SPD of selected nodes or lesions at baseline
4.2.2.
Tocilizumab and Steroid use after Anti-CD19 CAR T Cells Infusion
Post-baseline tocilizumab and steroid use may be used to examine efficacy in subgroups or 
covariate analyses:

Tocilizumab use after Anti-CD19 CAR T cells infusion (Y/N)

Steroids use after Anti-CD19 CAR T cells infusion (Y/N)

Tocilizumab or steroids use after Anti-CD19 CAR T cells (Y/N)

Tocilizumab and steroids use after Anti-CD19 CAR T cells (Y/N)
Covariate levels that are sparse may be collapsed for purposes of statistical modeling.


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5.
DEFINITIONS
5.1.
General
Study enrollment:  Study enrollment occurs when a subject commences leukapheresis. 
Study Day 0: Day 0 is defined as the day the subject receives the first anti-CD19 CAR T cells
infusion. The day prior to Day 0 will be Day –1. Any days after enrollment and prior to Day –1 
will be sequential and negative integer-valued.
Baseline:  The baseline value is defined as the last value taken prior to conditioning 
chemotherapy.
Study therapy:  Study therapy includes conditioning chemotherapy and anti-CD19 CAR T cells.
On-study:  Time from enrollment to the last date of contact.
End of study:  Defined as when the last subject is assessed or received an intervention for 
evaluation in the study, including survival assessments.
Relapsed/Refractory subgroup:  Relapsed/refractory subgroups are defined as below.  Subjects 
meeting both “Relapsed after SCT” and any of the other categories will be categorized as 
“Relapsed after SCT.”  Note that bridging therapies should not be included for defining the 
Relapsed/Refractory subgroups.

Relapsed after SCT:  A subject is considered to be relapsed after SCT if the subject 
experienced relapse (nonresponse, disease recurrence or disease progression) after SCT.

Refractory to last MCL therapy:  A subject is considered to be refractory to the last MCL 
therapy if the subject failed to achieve a PR or CR to the last MCL therapy.

Relapsed after last MCL therapy:  A subject is considered to be relapsed after last MCL 
therapy if the subject responded and subsequently experienced disease progression after the 
last MCL chemotherapy.
Bulky disease:  Bulky disease is defined as the presence of a single lesion with largest diameter 
being 10 cm or larger or mediastinum wider than 1/3 of the chest on a chest x-ray.  The presence 
of bulky disease will be determined by the investigator when baseline disease extent is evaluated.
Actual follow-up time:  Actual follow-up time among all subjects treated with anti-CD19 CAR 
T cells is calculated as the time from the first dose of anti-CD19 CAR T cells to the date of 
death, last date known to be alive, lost to follow-up, or full withdrawal of consent, whichever is 
later.
Potential follow-up time:  Potential follow-up time is defined as the time from the anti-CD19 
CAR T cells infusion to the data cutoff date for the analysis.


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5.2.
Safety
Treatment-emergent adverse event (TEAE): Any adverse event with onset on or after the 
anti-CD19 CAR T cells infusion. All TEAEs will be summarized by preferred term and toxicity 
grade. AEs occurred within other study periods may be summarized as appropriate. For subjects 
taking retreatment of KTE-X19/axicabtagene ciloleucel, TEAEs during retreatment period may
be summarized separately. 
Deaths:  All deaths that occur from the beginning of the chemotherapy conditioning period up 
through the end of study will be summarized. Deaths that occur from the anti-CD19 CAR T 
cells infusion up through 30 days after the infusion will also be summarized. For subjects taking 
retreatment of KTE-X19/axicabtagene ciloleucel, deaths occurred during retreatment period may 
also be summarized separately.
AEs of special interest:  Adverse events of special interest for KTE-X19/axicabtagene ciloleucel
treatment include identified risks (CRS, neurologic events, cytopenias, infections, and 
hypogammaglobulinemia) and potential risks (immunogenicity, secondary malignancies, RCR,
and tumor lysis syndrome [TLS]).
CRS will be identified via collection of the syndrome on a case report form (CRF) specifically 
designed to record CRS.  Specific individual symptoms of CRS (eg, fever) collected on the AE 
log will be coded using Medical Dictionary for Regulatory Activities (MedDRA) and linked to 
the corresponding CRS episode.  Individual symptoms of CRS will be graded per Common 
Terminology Criteria for Adverse Events (CTCAE) v 4.03, and CRS as a syndrome will be 
graded per modified Lee criteria ((Lee et al, 2014).  In the modified grading scale, neurologic 
AEs are not to be reported as part of the CRS syndrome and will be reported separately and 
summarized separately. 
Neurologic events will be identified with a search strategy based on known neurologic toxicities 
associated with anti-CD19 immunotherapy ({Topp 2015}).  The search strategy focuses on 
central nervous system (CNS) toxicity, without regard to relatedness, temporal relationship, or 
concomitant conditions (eg, CRS). Additionally, the MedDRA system organ classes (SOCs) of 
Psychiatric Disorders and Nervous System Disorders will be reviewed for additional events; 
these events will then be evaluated for potential inclusion as neurologic AEs.
Immunogenicity will be identified by the development of antibodies to antibodies against CAR 
expressing cells by flow cytometry.  In addition, a manual review of the AE terms indicative of 
autoimmunity, inclusive of infusion-related events and anaphylactic reactions among subjects 
who test positive for anti-CD19 CAR antibodies, will be performed.
For other AEs of special interest, specific adverse events may be mapped to these categories 
using dictionary coded event term and standardized MedDRA queries (SMQs) or other search 
strategies.  Specific definitions of these events and the coded terms to which they correspond will 
be provided in the Program Safety Analysis Plan. 


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Duration of an AE of special interest:  The duration of an AE of special interest may be 
derived only among subjects for whom all events of the class have resolved by the analysis data 
cutoff date.  The duration is defined as the stop day of the last AE in the event class – the start 
day of the first AE in the event class + 1.  
5.3.
Efficacy
ORR:  ORR is the proportion of subjects with either a CR or PR while on study.  All subjects 
who do not meet the criteria for objective response by the analysis data cutoff date will be 
considered non-responders, including the subjects with non-evaluable assessment data and those 
without any assessment. The derivation of this endpoint will only include response assessments 
obtained prior to any other additional therapy (eg, SCT or subsequent anti-cancer therapy or 
retreatment with anti-CD19 CAR T cells).  Response may be defined per Central Read or
Investigator Read.
DOR:  DOR is defined only for subjects who experience an objective response and is the time 
from the first objective response to disease progression or death.  Response and progression may 
be defined per Central Read or Investigator Read.  Data from retreatment period will not be 
included for analysis. Subjects not meeting the criteria for progression or death by the analysis 
data cutoff date will be censored at their last evaluable disease assessment date.  DOR will be 
derived using disease assessments obtained on study prior to initiation of new anti-cancer 
therapy (including SCT).  The DOR for subjects who undergo SCT while in remission will be 
censored at the last evaluable disease assessment date prior to SCT; the DOR for subjects that 
undergo other new anti-cancer therapies including the retreatment with anti-CD19 CAR T cells
in the absence of documented relapse will be censored at the last evaluable disease assessment 
prior to the new anti-cancer therapies. A sensitivity analysis will be conducted in which disease 
assessments obtained after SCT are included in the derivation of DOR. Additional details on the
derivation of DOR are provided in Appendix 3. In case that 5% or more subjects with two or 
more consecutive disease assessments missed prior to receiving SCT or new anti-cancer therapy, 
another sensitivity analysis will be performed with such subjects being counted as events and 
their DOR event time imputed based on the first missed scheduled assessment visit prior to the 
SCT or new anti-cancer therapy.
PFS:  PFS is defined as the time from the anti-CD19 CAR T cells infusion date to the date of 
disease progression or death from any cause. For PFS analysis with the full analysis set (defined 
in Section 6.4) in which enrolled but not treated subjects are included, the PFS time will be 
calculated. as the time from the enrollment date to the date of disease progression or death from 
any cause. Progression may be defined per Central Read or Investigator Read.  Data from 
retreatment period will not be included for analysis. Subjects alive and not meeting the criteria 
for progression by the analysis data cutoff date will be censored at their last evaluable disease 
assessment date.  PFS will be derived using disease assessments obtained on study prior to 
initiation of new anti-cancer therapy (including SCT). The PFS for subjects who undergo SCT 
while in remission will be censored at the last evaluable disease assessment date prior to SCT; 
the PFS for subjects that undergo other new anti-cancer therapies in the absence of documented 
relapse will be censored at the last evaluable disease assessment prior to the new anti-cancer 


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therapies. A sensitivity analysis will be conducted in which disease assessments obtained after 
SCT are included in the derivation of PFS. Additional details on the derivation of PFS are
provided in Appendix 3.
OS:  OS is defined as the time from the anti-CD19 CAR T cells infusion to the date of death
from any cause.  Subjects who have not died by the analysis data cutoff date will be censored at 
the last date known to be alive or the data cutoff date, whichever is earlier. For OS analysis with 
the full analysis set, the OS time will be calculated as the time from the enrollment date to the 
date of death from any cause. Additional details on the derivation of overall survival and the 
specific data modules that will be used to derive the last date known to be alive are provided in 
Appendix 3.  
Duration of response to retreatment (DORR):  DORR is defined the same as DOR, except 
that the definition applies to the response after KTE-X19/axicabtagene ciloleucel retreatment.


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6.
ANALYSIS SETS
Analysis sets are defined within each cohort as follows.
6.1.
Modified Intent-to-treat
The mITT analysis set will consist of all subjects enrolled and treated with any dose of 
anti-CD19 CAR T cells.  This analysis set will be used for efficacy analyses for Cohort 1 
subjects treated with axicabtagene ciloleucel and Cohort 2 subjects.
6.2.
Inferential Analysis Set
The inferential analysis set will consist of the first 60 treated KTE-X19 subjects in Cohort 1. 
This analysis set will be used for efficacy analyses in Cohort 1 and also the hypothesis testing of 
the primary endpoint ORR at the time of the primary analysis.
6.3.
Safety Analysis Set
The safety analysis set is defined as all subjects treated with any dose of anti-CD19 CAR T cells
(same as mITT).
6.4.
Full Analysis Set
The full analysis set (FAS) will consist of all enrolled subjects and will be used for the summary 
of subject disposition. This analysis set will also be used for analyses of objective response rate 
and other key efficacy endpoints (BOR, DOR, PFS, and OS).
6.5.
mITT Retreatment Analysis Set
The mITT retreatment analysis set will consist of all subjects who undergo retreatment with any 
dose of anti-CD19 CAR T cells.  This set will be used for all retreatment efficacy analyses.
6.6.
Safety Retreatment Analysis Set
The safety retreatment analysis set will consist of all subjects who undergo retreatment with 
anti-CD19 CAR T cells.
Note that subjects treated with anti-CD19 CAR T cells to expanded access (ie, “compassionate 
use” subjects not treated under Protocol KTE-C19-102) will not be included in the safety 
analysis set or the mITT analysis set. 
6.7.
Subgroup Analysis Sets
Subgroup analyses of selected efficacy and safety endpoints may be performed for subgroups 
defined by the baseline covariates defined in Section 4.2.  


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7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES
7.1.
Interim Analysis
An independent DSMB will be chartered to make recommendations on study conduct.  The 
DSMB will meet 4 times during the study (Cohort 1 interim analysis 1, Cohort 1 interim analysis 
2, Cohort 1 interim analysis 4, and Cohort 2 interim analysis 1), as described in Section 3.1 and
Section 3.3.  The DSMB will review safety and efficacy data and will be chartered to make trial 
conduct recommendations based on the risk versus benefit of treatment with anti-CD19 CAR T 
cells. For Cohort 1, a rho (parameter = 0.30) beta spending function will be used to allocate the 
beta level between the futility analysis at Cohort 1 interim analysis 2 and the primary efficacy 
analysis. The non-binding futility boundary for this interim analysis is reached if no more than 
5 responders (≤5) out of 20 subjects are observed. 
Details of the DSMB composition and responsibilities may be found in the DSMB charter.  
In addition to the 4 interim analyses to be reviewed by DSMB, an additional interim analysis 
(Cohort 1 interim analysis 3) will be performed for a Kite internal review of the accumulating 
data of safety and efficacy (see Section 3.3). After the planned primary analysis of the study, 
additional efficacy and safety analyses may be performed to support regulatory interaction or 
publications.  These analyses will be descriptive.
7.2.
Assessment of Criteria to Pause Enrollment
As part of its oversight of the study, the DSMB will also assess criteria to pause enrollment after 
10, 20, 30, and 50 subjects treated with anti-CD19 CAR T cells in Cohort 1 have had the 
opportunity to be followed for 30 days.  Enrollment will be paused if any of the following 
criteria is met:

Incidence of Grade 5 KTE-X19/axicabtagene ciloleucel-related adverse events within 
30 days is > 10%.

Incidence of the following Grade 4 KTE-X19/axicabtagene ciloleucel-related adverse events 
lasting more than 7 days is > 33%:
Neurologic toxicities
CRS (per Lee 2014 criteria)
Other non-hematological serious adverse event (SAE)
Infection (treatment-related)


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The assessments of criteria to pause enrollment will be triggered when 10, 20, 30, and 
50 subjects have been treated with anti-CD19 CAR T cells and have had the opportunity to be 
followed for 30 days. At each assessment, the subject incidence of the events listed in the above 
criteria will be tabulated for the first treated 10 subjects, 20 subjects, 30 subjects, and 
50 subjects, respectively. If either criterion is met (with incidence rates calculated with 
10 subjects, 20 subjects, 30 subjects, and 50 subjects as denominators, respectively) prior to an
assessment milestone, the DSMB will proceed with the assessment with available data. 
7.3.
Access to Aggregate and Subject-level Data and Individual Subject 
Treatment Assignments
This study is open label.  Subjects, the study sponsor, and investigators will be aware that each 
subject is planned to be treated with KTE-X19/axicabtagene ciloleucel.  Data handling 
procedures designed to maintain the trial credibility and validity in this study are described in the 
Trial Integrity Document.
An independent statistician will perform Cohort 1 interim analysis 1, Cohort 1 interim analysis 2, 
Cohort 1 interim analysis 4, and Cohort 2 interim analysis for the study, as well as the safety 
assessment to pause enrollment, and provide these reports to the DSMB.  Members of the DSMB 
and independent statistician will not have any direct contact with study center personnel or 
subjects.  The DSMB will communicate recommendations to Kite Pharma in accordance with the 
DSMB charter. Additional details of the DMSB composition and reviews are described in the 
DSMB charter.


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8.
DATA SCREENING AND ACCEPTANCE
8.1.
General Principles
The database will be subject to the edit checks outlined in the Data Management Plan and 
additional manual data reviews defined by the study team.  Data inconsistencies will be reviewed 
and resolved before the database snapshot for the primary analysis and the final database lock.  
For interim analyses, snapshots may include data that has not passed all data cleaning procedures 
at the time the data are extracted for snapshot.  
8.2.
Electronic Transfer and Archival of Data
The Medidata Rave system will be used to collect the data in this study.  Raw data extracted 
from Medidata Rave will be archived prior to further dataset creation, maintenance, and analysis.  
Datasets (raw data, study data tabulation model [SDTM] data, and/or analysis data model 
[ADaM] data) for planned analyses will be archived.  Any additional unplanned analyses that 
occur after the primary analysis and prior to the final analysis will also be archived.  Key data 
external to the clinical study database (see below) will be included in the relevant SDTM and 
ADaM modules when the external data are available.
Data from the central pathology laboratory (including tumor pathology, tumor genetic, and 
molecular characteristics), the product manufacture (total T cells, CAR T cells [transduction 
ratio], duration of manufacturing time), central laboratory assessment of subject serum samples 
(including CAR T cell levels in the peripheral blood, antibody assays, RCR testing), and central 
radiology review will be generated from contract laboratories and Kite Pharma.  These data will 
be transferred to Kite and held in a peripheral directory and not built into the clinical trial 
database. At the time when analyses require these data, they may be merged with the SDTM and 
ADaM datasets.
8.3.
Handling of Missing and Incomplete Data
8.3.1.
Efficacy
The method for handling missing data is described in the definition for each efficacy endpoint.  
Every effort will be made to obtain complete dates for deaths.  In the event of a partial or missing 
death date and the corresponding censoring date for survival, the algorithm in Appendix 1 will be 
used.
8.3.2.
Safety
Partial AE start dates will be imputed.  If dates are missing or incomplete for adverse event start 
dates, the algorithm defined in Appendix 1 will be used.  Completely missing death dates or 
death dates with only a year reported will not be imputed.


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8.4.
Detection of Bias
A listing of subjects with important protocol deviations will be generated.  The deviations 
included in this list will include, but not be limited to, violations of eligibility criteria and use of 
exclusionary medication during the study.  Lack of protocol compliance will be evaluated by 
summarizing the subject incidence of important protocol deviations.  High rates of important 
protocol deviations may indicate bias.
Endpoints derived from investigator assessment of radiologic scans and disease assessments may 
be subject to bias; the concordance between investigator and central review of radiologic scans 
and disease assessments will be summarized where appropriate.
8.5.
Outliers
Descriptive statistics may be used to identify potential outliers in any key variables analyzed.  
Suspected outliers will be included in all analyses unless there is sufficient scientific justification 
to exclude them.
8.6.
Distributional Characteristics
The primary analysis of the primary endpoint is an exact binomial test used to compare the 
observed ORR per Central Read to a response rate of 25% in the Cohort 1 inferential analysis 
set.  This test assumes only the independence of the individual subject responses.  
An exact 95% confidence interval will be generated about the ORR.  The Clopper-Pearson 
method will be used to generate this interval.  While the Clopper-Pearson interval provides 
adequate coverage probability, it is commonly wider than necessary {Brown 2002}, leading to 
overly conservative estimates of the lower bound of objective response rate.  Sensitivity analyses 
will be conducted in which the interval is calculated with different methods (Section 9.5.1).
8.7.
Validation and Configuration Management
Programs for the development of the SDTM and ADaM datasets and the generation of the tables, 
figures, and listings will be developed and maintained according to Cytel Inc. Standard 
Operating Procedures (SOPs) and Kite SOPs if applicable. The software and version used to 
generate analyses will be indicated in the archived documentation.


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9.
STATISTICAL METHODS OF ANALYSIS
9.1.
General Principles
The goal of the primary statistical analysis is to compare the observed ORR per Central Read to 
a historical control rate of 25% with an exact binomial test in the Cohort 1 inferential analysis 
set. Hypothesis testing will be one-sided, and all 95% confidence intervals will be 2-sided.  At 
the time of the primary analysis, 95% confidence intervals for ORR will be presented for Cohort 
1 inferential analysis set subjects. ORR with 95% confidence intervals may be generated for 
Cohort 1 axicabtagene ciloleucel subjects, and Cohort 2 subjects, respectively, for descriptive 
purpose only.
The timing of the interim and primary analyses will be based on subject accrual and safety or 
disease assessment milestones. The primary analysis Clinical Study Report will be written at the 
primary analysis of the study.  The Clinical Study Report may be amended with additional 
subject safety and survival follow-up after the planned primary analysis.
9.2.
Subject Accountability
The number of subjects screened, enrolled/leukapheresed, treated with bridging therapy, treated 
with conditioning chemotherapy, treated with anti-CD19 CAR T cells, and retreated with 
anti-CD19 CAR T cells will be summarized.  The reasons for discontinuing treatment and 
discontinuing study will be summarized.
Summaries of actual and potential follow-up time among all subjects treated with anti-CD19 
CAR T cells will be provided.
The number of subjects enrolled by country and site will be summarized.  
The number of subjects in each analysis set will be provided.
9.3.
Important Protocol Deviations
The clinical study team will define important protocol deviation categories and review all 
potential important protocol deviations at minimum, prior to the database snapshot for the 
primary efficacy analysis.  Important protocol deviations will be categorized by deviation type 
(eg, entry eligibility, use of excluded medication).  The subject incidence of important protocol 
deviations will be summarized overall and by deviation category.
9.4.
Demographic and Baseline Characteristics
Summary statistics and frequencies for the demographic and baseline characteristics as listed in 
Section 4.2.1 will be tabulated.


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9.5.
Efficacy Analyses
The hypothesis testing of ORR will be conducted on the inferential analysis set. Other efficacy 
analyses will also be conducted on the inferential analysis set for Cohort 1 KTE-X19 subjects. 
FAS will also be used for analyses on key efficacy endpoints (ORR, BOR, DOR, PFS, and OS).
Efficacy analyses for Cohort 1 axicabtagene ciloleucel subjects and Cohort 2 subjects will be 
conducted on the mITT analysis set.  For the primary analysis, the IRRC assessments based on 
the Lugano Classification {Cheson 2014}, referred to as “Central Read,” will be used.  
Sensitivity analyses will be conducted based on the investigator assessments.  For Cohort 1, the 
Investigator Read will be based on the revised International Working Group Criteria for 
Malignant Lymphoma {Cheson 2007}; for Cohort 2, the investigator review will be based on the 
Lugano Classification {Cheson 2014}. The independent radiology reviewers and investigators 
will provide the determination of disease status (CR, PR, SD, PD, not evaluable [NE]) at each 
time point.  Statistical analysis system (SAS) programs will be used to derive the best overall 
response, DOR, and PFS based on these assessments. Efficacy analyses of Cohort 1 
axicabtagene ciloleucel subjects and Cohort 2 KTE-X19 subjects will be descriptive.
The analysis of objective response rate and DOR will be presented in the following analysis sets:

Inferential analysis set (Cohort 1 KTE-X19 subjects)

mITT analysis set (Cohort 1 axicabtagene ciloleucel and Cohort 2 subjects)

FAS (Cohort 1 KTE-X19 subjects)
Disease assessment obtained after retreatment will not be used in the primary summaries of 
objective and best response, DOR, and PFS.  For such subjects, disease assessments obtained 
after retreatment will be included in the summaries of objective and best response to retreatment 
with anti-CD19 CAR T cells and DORR.  The subject’s OS time will be derived from the last 
date known to be alive regardless of retreatment time.
In the event any subject undergoes an autologous or allogeneic SCT or any other anti-cancer 
therapy while on study, the subject’s best response will be derived only based on disease 
outcomes assessed prior to SCT or initiation of new therapy, whichever is earlier.  For subjects 
without documentation of progression prior to initiation of new therapy (including SCT), DOR
and PFS time will be censored at the last disease assessment prior to the initiation of new therapy
(including SCT).  A sensitivity analysis for DOR will be conducted in which disease assessments 
after SCT are included to derive events and censoring times for subjects who undergo SCT while 
in KTE-X19/axicabtagene ciloleucel-induced response.  (See details in Appendix 3.)  


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9.5.1.
ORR and Best Response
9.5.1.1.
Primary Analyses of ORR per Central Read
The subject incidence of objective response per Central Read will be calculated.  The subject 
incidence of best response (CR, PR, SD, PD, NE) per Central Read will be tabulated.  
Confidence intervals will be provided about the ORR and best response, calculated with the 
following methods:

Clopper-Pearson (an exact interval)

Wilson’s method (sensitivity analysis)

Agresti-Coull method (sensitivity analysis)

The modified Jeffrey’s method {Brown 2001} (sensitivity analysis)
An exact binomial test will be used to compare the observed ORR per Central Read to the 
hypothesized historical control rate of 25% for the inferential analysis set subjects only. 
The analysis of ORR and best response per Central Read will include subjects from the 
Inferential analysis set for Cohort 1 and mITT set for Cohort 2.  Analysis of objective response 
in Cohort 1 KTE-X19 subjects will also be conducted using the FAS.
9.5.1.2.
Analyses of Objective Response and Best Response per Investigator Read
The analyses of ORR and best response specified above will be repeated for ORR and best 
response per Investigator Read.
The concordance of objective response and best response per Central Read and Investigator Read 
will be evaluated in Cohort 1.  A summary table of concordance, concordance rate, a kappa 
statistic, and a 2-sided 95% confidence interval about the kappa statistic will be provided.
Further analyses comparing the Investigator and Central Reads may be performed as appropriate.
9.5.1.3.
Subgroup Analyses of ORR
ORR and 95% confidence intervals will be generated for subgroups defined by each of the 
categorical covariates in Section 4.2.1 of the inferential analysis set of Cohort 1 KTE-X19
subjects. Subgroup analysis with additional covariates may also be explored.
A forest plot of the proportion of responders for each of these subgroups will be generated.  


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9.5.2.
DOR  
The Kaplan-Meier approach will be used to estimate DOR. The number of subjects censored 
and the reasons for censoring will be summarized.  Analyses will be generated for DOR per 
Central Read, as well as per Investigator Read.  The reverse Kaplan-Meier approach {Schemper 
1996} will be used to estimate the follow-up time for DOR.   
A sensitivity analysis of DOR will be conducted in which disease assessments obtained after 
SCT (for subjects who undergo SCT while in a KTE-X19/axicabtagene ciloleucel induced 
response) are used in the derivation of DOR. In case that 5% or more subjects with two or more 
consecutive disease assessments missed prior to receiving SCT or new anti-cancer therapy, 
another sensitivity analysis will be performed with such subjects being counted as events and 
their DOR event time imputed based on the first missed scheduled assessment visit prior to the 
SCT or new anti-cancer therapy.
An analysis of DOR will also be conducted in the FAS for Cohort 1 KTE-X19 subjects.  
DOR may be summarized in subgroups defined by the best response attained on study.
9.5.3.
PFS
Kaplan-Meier plots, estimates, and 2-sided 95% confidence intervals will be generated for PFS.  
Estimates of the proportion of subjects alive and progression-free at 3-month intervals will be 
provided.  The number of subjects censored and the reasons for censoring will be summarized.  
Analyses will be generated for PFS per Central Read and PFS per Investigator Read.
A sensitivity analysis will be conducted in which disease assessments obtained after SCT (for 
subjects undergoing SCT while in a KTE-X19/axicabtagene ciloleucel induced response) are 
included in the derivation of PFS.
A PFS analysis will also be conducted in the FAS.
Subgroup analyses of the PFS rate at 6 months may be generated in subgroups defined by the 
covariates in Section 4.2.
PFS may be summarized in subgroups defined by the best response attained on study.
9.5.4.
OS
The analysis of OS will use the same methods as the analysis of PFS. An OS analysis will also 
be conducted in the FAS.
OS may be summarized in subgroups defined by the best response attained on study.


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9.5.5.
Tumor Burden
The change in tumor burden, as measured by the SPD of the selected lesions (reported as target 
lesions), from baseline to post-baseline nadir will be summarized in absolute numbers (mm2) and 
percentage.  A graphical summary of this change will be presented in a vertical bar chart with 
each subject’s percent change from baseline to nadir displayed as a vertical bar, with color 
coding that indicates best response attained (“waterfall” plot). Analyses will be generated for 
change in tumor burden per Central Read and per Investigator Read. Data collected after new 
anti-cancer therapy, retreatment of anti-CD19 CAR T cells, or SCT will not be included for the 
analyses.
9.5.6.
Objective Response and Best Response Among Subjects Retreated with Anti-
CD19 CAR T Cells
The incidence of subjects retreated with anti-CD19 CAR T cells will be tabulated or listed.  ORR 
and best response (CR, PR, SD, PD, NE) to the retreatment among subjects retreated with 
anti-CD19 CAR T cells will be calculated.  Confidence intervals may be provided about the 
ORR and best response to the retreatment.  Analyses may be conducted per Central Read and 
Investigator Read.
9.5.7.
DORR
The analysis of DORR may be conducted using the same methods as the analysis of DOR.
9.5.8.
Incidence of SCT
The subject incidence of SCT post-treatment with anti-CD19 CAR T cells and prior to disease 
progression will be tabulated among subjects who undergo SCT while in KTE-X19/axicabtagene 
ciloleucel induced response. 
9.5.9.
European Quality of Life-5 Dimensions and Visual Analogue Scale Scores
EQ-5D and VAS scores will be summarized at baseline and post study treatment visits. Changes 
in the EQ-5D-5L and VAS scores from baseline at each post-study treatment visit will also be 
summarized with descriptive statistics.
Further analyses of these quality of life data may be described in a supplemental statistical 
analysis plan.
9.6.
Safety Analyses
Safety analyses will be conducted on the safety analysis set for Cohort 1 KTE-X19 subjects, 
Cohort 1 axicabtagene ciloleucel subjects, and Cohort 2 subjects, respectively. Safety analysis
will also be conducted on the treated KTE-X19 subjects combined from Cohort 1 and Cohort 2.
The primary analysis of safety data will summarize TEAEs, death, and laboratory values with 
onset on or after the anti-CD19 CAR T cells infusion date and prior to retreatment period 


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(if applicable).  Additional summary tables may be provided to present the AEs that occurred 
within certain study periods.  For subjects who undergo retreatment with anti-CD19 CAR T 
cells, AEs occurring in the retreatment period may be summarized or listed separately.  Sample 
table layouts are provided in Appendix 2.
AEs will be coded with the MedDRA at the time of each analysis.  The version of the MedDRA 
may vary over time as the current version in use is updated.  The severity of AEs will be graded 
using the National Cancer Institute CTCAE version 4.03.  
CRS will be graded using a revised CRS grading scale developed by Lee et al {Lee 2014}.  The 
incidence and severity of CRS will be reported as a syndrome with severity per Lee et al {Lee 
2014}.  Individual symptoms associated with CRS will be graded per CTCAE version 4.03. Fatal 
AEs that are attributed to disease progression may be included in the death summary with a 
primary death reason of “disease progression” regardless of the coded CTCAE version 4.03 
preferred term.
Subjects enrolled, but not dosed with anti-CD19 CAR T cells, will be followed for AEs for 
30 days after the last study-specific procedure.  AEs reported in these subjects will be archived in 
the study database and available in SDTM and ADaM datasets, but will not be tabulated in AE
summaries.
9.6.1.
AEs
The subject incidence of the following TEAEs will be tabulated:

Summary of AEs (any, worst severity, serious, treatment-related)

All AEs

All SAEs

All KTE-X19/axicabtagene ciloleucel-related AEs

All KTE-X19/axicabtagene ciloleucel-related SAEs

All Grade 3 or higher AEs

All Grade 3 or higher KTE-X19/axicabtagene ciloleucel-related AEs

Fatal AEs

AEs of special interest, including identified risks and potential risks 
The subject incidence of deaths by time periods will be provided.   


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A subject listing of deaths through 30 days after anti-CD19 CAR T cells infusion   will be 
provided overall and by treatment period.
Subgroup analyses of AEs may be generated for selected covariates from the list in Section 4.2.1.  
The time to onset and resolution and the duration of CRS will be summarized. Cardiac 
arrhythmias and cardiac failure in the context of CRS may be summarized. 
The time to onset and resolution and the duration of neurologic events will be summarized. 
Cytopenias will be summarized by categories of neutropenia, anemia, and thrombocytopenia; 
cytopenias present after 30 days from anti-CD19 CAR T cells infusion will also be summarized.
Infections will be summarized by categories (bacterial infections, viral infections, opportunistic 
infections, and other infections).
9.6.2.
Procedures and Concomitant Medications
The incidences of procedure and concomitant medications used to manage AEs will be tabulated
(see Section 9.6.7).
9.6.3.
Laboratory Test Results
Laboratory results will be graded according to National Cancer Institute CTCAE version 4.03.  
The incidence of post-infusion worst-grade lab toxicities for all analytes will be summarized.
Additional summaries for the shift from baseline to the worst toxicity grade after anti-CD19 
CAR T cells infusion may also be generated.
9.6.4.
Anti-CD19 CAR Antibodies
The subject incidence of any anti-CD19 CAR antibodies will be tabulated.  For subjects testing 
positive for antibodies, the persistence of the antibody over time will be listed and summarized.
9.6.5.
RCR
The subject incidence of RCR detected in blood samples will be tabulated overall and by 
assessment time.  The persistence of RCR over time will be summarized.
9.6.6.
Exposure to Study Treatment  
Summary statistics and subject listings will be provided for the following:

Total body surface area-adjusted dose of cyclophosphamide

Total body surface area-adjusted dose of fludarabine

Weight-adjusted dose of KTE-X19/axicabtagene ciloleucel


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
Total CAR T cells of the KTE-X19/axicabtagene ciloleucel infusion

Total T cells of the KTE-X19/axicabtagene ciloleucel infusion

Transduction ratio

Percentages of CD4 and CD8 T cells

Percentages of T cell memory phenotypes

Interferon (IFN)-gamma production in co-cultures of KTE-X19/axicabtagene ciloleucel
product and CD19+ target cells

Vector copy number of KTE-X19/axicabtagene ciloleucel product
Summaries may also be provided by demographics and baseline characteristics as appropriate. 
Separate summaries will be presented for the retreatment conditioning chemotherapy and 
KTE-X19/axicabtagene ciloleucel for subjects in the retreatment analysis set.
9.6.7.
Exposure to Concomitant Medications and Procedures
The subject incidence of concomitant medications will be summarized by medication category 
and WHO Drug coded term.   The subject incidence of procedures will be tabulated. The 
duration and indication of concomitant medications of interest, steroids and tocilizumab for 
example, may be summarized. 
9.6.8.
Mini-mental Status Exam
Summary statistics for the Mini-Mental Status Exam score and change from baseline in the 
Mini-Mental Status Exam score over time will be provided for all subjects in the safety analysis 
set and may be summarized within groups defined by the occurrence of Grade 3 or higher 
neurotoxicity.  
9.7.
Subsequent Anti-cancer Therapy
The incidence of subsequent anti-cancer therapy (by WHO Drug coded term) will be 
summarized.
9.8.
Schedule of Study Treatment
Summary statistics will be provided for the following durations:

Days from leukapheresis to KTE-X19 product release

Days from leukapheresis to receipt of anti-CD19 CAR T cells at the study site 

Days from leukapheresis to administration of anti-CD19 CAR T cells

Duration of hospitalization for the anti-CD19 CAR T cells infusion


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9.9.
CAR T Cells Measured in Peripheral Blood
Summary statistics for the level of CAR T cells in serum post KTE-X19/axicabtagene ciloleucel
infusion will be provided for CAR T cells measured at Day 7, Week 2, Week 4, Month 3, 
Month 6, Month 12, and Month 24.  The maximum CAR T cell level attained, the time at which 
the maximum level was attained, and the time at which there were no detectable CAR T cells in 
the serum will be summarized.  The area under the concentration over time curve may be 
summarized from Day 0 to Day 28.
9.10.
B-cell Aplasia
The subject incidence of B-cell aplasia based on B cells measured by flow cytometry and the 
subject incidence of recovery of B-cells aplasia will be summarized. The use of intravenous 
immunoglobulin may be summarized.


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10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES
None.


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11.
REFERENCES
Brown LD, Cai TT, DasGupta A. Interval Estimation for a Binomial Proportion. Statistical 
Science 2001;16 (2):101-33.
Brown LD, Cai TT, DasGupta A. Confidence Intervals for a Binomial Proportion and 
Asymptotic Expansions. The Annals of Statistics 2002;30 (1):160-201.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. 
Recommendations for initial evaluation, staging, and response assessment of 
Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 
2014;32 (27):3059-68.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised 
response criteria for malignant lymphoma. J Clin Oncol 2007;25 (5):579-86.
Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, et al. A 
new prognostic index (MIPI) for patients with advanced-stage mantle cell 
lymphoma. Blood 2008;111 (2):558-65.
Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M, et al. Current concepts in the 
diagnosis and management of cytokine release syndrome. Blood 2014;124 
(2):188-95.
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin 
Trials 1996;17 (4):343-6.
Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity 
of blinatumomab for adult patients with relapsed or refractory B-precursor acute 
lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet 
Oncology 2015;16 (1):57-66.


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12.
HISTORY OF REVISIONS
Version
Date
Protocol
Description of Changes
Original (1.0)
15JUN2017
Original to 
Amendment 3
N/A
2.0
17NOV2017
Amendment 4

Added Cohort 2 as pivotal cohort (N=40) and changed 
Cohort 1 to non-pivotal cohort and decreased Cohort 1 
sample size from N=67 to N=40;

Modified the interim and primary analyses accordingly;

Changed the primary efficacy endpoint from objective 
response rate (ORR) based on investigator read per 
Cheson 2007 to ORR based on Central Read per Lugano 
Classification (Cheson 2014);

Changed the hypothesis testing on ORR from 40% vs. 
20% to 50% vs. 25%; 

Added QoL (EQ-5D and VAS score) and RCR incidence 
rate as secondary endpoints;

Added prior acalabrutinib to baseline characteristics 
summary;

Other minor or cosmetic changes.
3.0
23APR2018
Amendment 4

Removed B-cell aplasia analysis; 

Simplified the section of definitions; 

Updated the potential risks and the analysis method;

Added language for QoL (EQ-5D and VAS score) 
summary;

Other minor or cosmetic changes.
4.0
12JUL2018
Amendment 5

Specified that Cohort 1 KTE-X19 subjects will form the 
basis for statistical hypothesis testing on the primary 
endpoint;

Increased the sample size of Cohort 1 from N=40 to 
N=~90 (with at least 60 XLP subjects); 

Specified that no hypothesis will be tested in the Cohort 1 
axicabtagene ciloleucel subjects or Cohort 2 subjects;

Added an interim analysis to Cohort 1; 

Changed the primary analysis time based on Cohort 1 
enrollment (ie, after 60 C1 KTE-X19 subjects have had 
the opportunity to be evaluated for response 6 months 
after week 4 disease assessment); 

Removed competing-risk analysis on DOR;

Other minor or cosmetic changes.


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Version
Date
Protocol
Description of Changes
5.0
22OCT2018
Amendment 6

Changed investigational product name from KTE-C19 to 
KTE-X19; 

Added a sensitivity analysis on DOR in the event of 5% 
or more subjects with two or more consecutive disease 
assessments missed prior to receiving SCT or new 
anti-cancer therapy;

Indicated that inferential analysis set will be used for all 
key efficacy analyses; 

Indicated that full analysis set will be used for efficacy 
analysis on ORR and other key efficacy endpoints;

Other minor or cosmetic changes.
6.0
8JUL2019
Amendment 6

Specified that inferential analysis set and FAS will be 
used for efficacy analyses in Cohort 1 KTE-X19 subjects 
while mITT set will be used for Cohort 1 axicabtagene 
ciloleucel and Cohort 2 efficacy analysis;

Added the PFS and OS definitions for FAS;

Indicated that safety analysis will also be done with all 
treated KTE-X19 subjects combined from Cohort 1 and 
Cohort 2;

Added back B-cell aplasia analysis;

Added summary for history of revisions; 

Other minor or cosmetic changes.


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Statistical Analysis Plan
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KTE-C19-102 (ZUMA-2)
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08 July 2019
13.
APPENDICES
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or 
Missing Dates
The following data will be imputed using the following algorithm:

Adverse event (AE) start dates

Deaths (see exceptions below)

Concomitant medication start dates

Subsequent anti-cancer therapy start dates
Table 1.
Imputation Rules for Partial or Missing Start Dates
Start Date
Stop Date
Complete:  yyyymmdd
Partial:  yyyymm
Partial:  yyyy
Missing
< Day 0
≥ Day 0
< Day 0 
yyyymm
≥ Day 0
yyyymm
< Day 0 
yyyy
≥ Day 0
yyyy
Partial
yyyymm
= Day 0
yyyymm
2
1
2
1
n/a
1
1
≠ day 0
yyyymm
2
2
2
2
2
Partial
yyyy
= Day 0
yyyy
3
1
3
1
n/a
1
1
≠ Day 0
yyyy
3
3
3
3
3
Missing
4
1
4
1
4
1
1
Abbreviation:  n/a, not applicable.
Note:  If the start date imputation leads to a start date that is after the stop date, then do not impute the start date.
1 = impute the date of Day 0.
2 = impute the first of the month.
3 = impute January 1 of the year.
4 = impute January 1 of the stop year.
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KTE-C19-102 (ZUMA-2)
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Imputation rules for partial or missing death dates:

If death year and month are available, but day is missing:
If mmyyyy for the last date known to be alive = mmyyyy for death date, set death date to 
the day after the last date known to be alive.
If mmyyyy for the last date known to be alive < mmyyyy for death date, set death date to 
the first day of the death month.
If mmyyyy for last date known to be alive > mmyyyy for death date, data error and do 
not impute.

If both month and day are missing for death date or a death date is completely missing, do 
not impute, and censor the subject survival time at the analysis data cutoff date or the last 
date known to be alive, whichever is later.


KTE-X19
Statistical Analysis Plan
Kite Pharma, Inc.
KTE-C19-102 (ZUMA-2)
Final
CONFIDENTIAL
Page 39
08 July 2019
Appendix 2.
Sample Adverse Event Table Layouts
Sample Adverse Event (AE) Summary Layout 1:  All AE summaries listed in Section 9.6.1
will be provided in format 1 (“Gr 1” and “Gr 2” columns are not needed for “Grade 3 or higher” 
summary tables).  The preferred terms will be sorted by descending order of frequency of the 
“Any” column.
Table 2.
Subject Incidence of <AE Descriptor> AEs by Preferred Term 
(Worst Grade)
Any
Gr 1
Gr2
Gr 3
Gr 4
Gr 5
Any <AE descriptor> adverse event 
– n(%)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
Preferred term 1
XX (X)
XX (X) 
XX (X)
XX (X)
XX (X)
XX (X)
Preferred term 2
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
Abbreviations:  AE, adverse event; Gr, Grade.
Sample Adverse Event Summary Layout 2:  AE summaries may also be provided in format 2
(“Gr 1” and “Gr 2” columns are not needed for “Grade 3 or higher” summary tables).  The 
system organ classes and preferred terms will be sorted by alphabetical order of system organ 
class and descending incidence of preferred term within each system organ class.
Table 3.
Subject Incidence of <AE Descriptor> AEs by System Organ Class 
and Preferred Term (Worst Grade)
Any
Gr 1
Gr 2
Gr 3
Gr 4
Gr 5
Any <AE descriptor> adverse event 
– n(%)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
System Organ Class 1
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
     Preferred term 1
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
     Preferred term 2
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
System Organ Class 2
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
XX (X)
…
Abbreviations:  AE, adverse event; Gr, Grade.


KTE-X19
Statistical Analysis Plan
Kite Pharma, Inc.
KTE-C19-102 (ZUMA-2)
Final
CONFIDENTIAL
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08 July 2019
Appendix 3.
Derivation of Time to Event Endpoints and Last Date Known to Be 
Alive
Additional detail on the derivations of duration of response (DOR), duration of response to 
retreatment (DORR), progression-free survival (PFS), and overall survival (OS) is provided 
below.
1) DOR
DOR is defined only for subjects who experience an objective response (CR or PR) and is the 
time from the first objective response to disease progression or death.  Response and progression 
may be defined per Central Read or Investigator Read. Data from retreatment period will not be 
included for analysis. Subjects not meeting the criteria for progression or death by the analysis 
data cutoff date will be censored at their last evaluable disease assessment date.  DOR will be 
derived using disease assessments obtained on study prior to initiation of new anti-cancer 
therapy.  The DOR for subjects who undergo stem cell transplant (SCT) while in remission will 
be censored at the last evaluable disease assessment date prior to SCT; the DOR for subjects that 
undergo other new anti-cancer therapies in the absence of documented relapse will be censored 
at the last evaluable disease assessment prior to the new anti-cancer therapies. A sensitivity 
analysis will be conducted in which disease assessments and death information obtained after 
SCT are included in the derivation of duration of response.  
Table 4.
Primary Analysis of DOR
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression prior to initiation of new 
anti-cancer therapy (including SCT)
Event
Progression date
Death without documented disease progression and 
without new anti-cancer therapy (including SCT)
Event
Death date
Remain in response without new anti-cancer 
therapy (including SCT) 
Censored
Last evaluable disease assessment date
Initiated new anti-cancer therapy (including SCT) 
prior to documented progression or death
Censored
Last evaluable disease assessment date 
prior to initiation of new therapy
including SCT
Remain in response without new anti-cancer 
therapy (including SCT) until withdrawal of consent 
or loss to follow-up
Censored
Last evaluable disease assessment date 
Abbreviations:  DOR, duration of response; SCT, stem cell transplant. 


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Table 5.
Sensitivity Analysis of DOR (to include data after SCT post study 
treatment)
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression after SCT, but prior to other 
new anti-cancer therapy
Event
Progression date
Death after SCT without documented progression
and other new anti-cancer therapy
Event
Death date
Remain in response after SCT without other new 
anti-cancer therapy
Censored
Last evaluable disease assessment date
after SCT
Remain in response after SCT prior to other 
initiated new anti-cancer therapy
Censored
Last evaluable disease assessment date 
after SCT but prior to other initiated 
new anti-cancer therapy
For subjects without SCT and all the other circumstances, follow the same as the “Primary Analysis of DOR.”
Abbreviations:  DOR, duration of response; SCT, stem cell transplant. 
2) DORR
DORR is defined the same as DOR, except that the definition applies to the response after 
KTE-X19/axicabtagene ciloleucel retreatment.  
3) PFS
PFS is defined as the time from the anti-CD19 CAR T cells infusion date to the date of disease 
progression or death from any cause.  Progression may be defined per Central Read or 
Investigator Read. For PFS analysis with the full analysis set in which enrolled but not treated 
subjects are included, the PFS time will be calculated as the time from the enrollment date to the 
date of disease progression or death from any cause. Data from retreatment period will not be 
included for analysis. Subjects alive and not meeting the criteria for progression by the analysis 
data cutoff date will be censored at their last evaluable disease assessment date.  PFS will be 
derived using disease assessments obtained on study prior to initiation of new anti-cancer 
therapy (including SCT).  The PFS for subjects who undergo SCT while in remission will be 
censored at the last evaluable disease assessment date prior to SCT; the PFS for subjects that 
undergo other new anti-cancer therapies in the absence of documented relapse will be censored 
at the last evaluable disease assessment prior to the new anti-cancer therapies. A sensitivity 
analysis will be conducted in which disease assessments and death information obtained after 
SCT are included in the derivation of PFS.


KTE-X19
Statistical Analysis Plan
Kite Pharma, Inc.
KTE-C19-102 (ZUMA-2)
Final
CONFIDENTIAL
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Table 6.
Primary Analysis of PFS
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression prior to initiation of new 
anti-cancer therapy (including SCT)
Event
Progression date
Death without documented disease progression and 
without new anti-cancer therapy (including SCT)
Event
Death date
Remain in response and alive without new 
anti-cancer therapy (including SCT) 
Censored
Last evaluable disease assessment 
date
Initiated new anti-cancer therapy (including SCT) 
prior to documented progression or death
Censored
Last evaluable disease assessment date 
prior to initiation of new therapy
including SCT. If no evaluable disease 
assessment is available, then censor at 
anti-CD19 CAR T cells infusion date
Remained in response without new anti-cancer 
therapy (including SCT) until withdrawal of consent 
or loss to follow-up 
Censored
Last evaluable disease assessment 
date. If no evaluable disease 
assessment is available, then censor at 
anti-CD19 CAR T cells infusion date
Subject enrolled and treated with anti-CD19 CAR T 
cells but the disease assessment has not been done
Censored
Anti-CD19 CAR T cells infusion date
Abbreviations:  PFS, progression-free survival; SCT, stem cell transplant.
Table 7.
Sensitivity Analysis of PFS
Circumstance
Event/Censored
Date of Event/Censoring
Disease progression after SCT, but prior to other 
new anti-cancer therapy
Event 
Progression date
Death after SCT without documented progression
and other new anti-cancer therapy
Event
Death date
Remain in response after SCT without other new 
anti-cancer therapy
Censored
Last evaluable disease assessment date
after SCT
Remain in response after SCT prior to other 
initiated new anti-cancer therapy
Censored
Last evaluable disease assessment date 
after SCT but prior to other initiated 
new anti-cancer therapy
For subjects without SCT and all the other circumstances, follow the same derivation rule as the “Primary Analysis 
of PFS.”
Abbreviations:  PFS, progression-free survival; SCT, stem cell transplant.
4) OS
OS is defined as the time from the anti-CD19 CAR T cells infusion to the date of death from any 
cause. For OS analysis with the full analysis set, the OS time will be calculated as the time from 
the enrollment date to the date of death from any cause. Subjects who have not died by the 
analysis data cutoff date will be censored at the last date known to be alive or the data cutoff 
date, whichever is earlier.


KTE-X19
Statistical Analysis Plan
Kite Pharma, Inc.
KTE-C19-102 (ZUMA-2)
Final
CONFIDENTIAL
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08 July 2019
Table 8.
Analysis of OS
Circumstance
Event/Censored
Date of Event/Censoring
Death before data cutoff date for analysis
Event
Date of death
Death after data cutoff date for analysis
Censored
Data cutoff date
Known to be alive after data cutoff date for analysis
Censored
Data cutoff date
Alive up through data cutoff date and no further 
information available after data cutoff date
Censored
Last date known to be alive 
Full withdrawal of consent or lost to follow-up prior 
to data cutoff date
Censored
Last date known to be alive 
Abbreviation:  OS, overall survival.
5) Last Date Known to be Alive
The last date known to be alive with be derived by obtaining the maximum complete date among 
the following data modules:

Start date of AE

Leukapheresis dates

Bridging therapy administration dates

Conditioning chemo administration dates

anti-CD19 CAR T cells infusion dates

Computerized tomography (CT) scan dates

Positron emission tomography (PET) scan dates

Clinical symptoms of lymphoma assessment dates

Target lesion assessment

Non-target lesion assessment

New lesion assessment

Other tumor assessment dates (Bone marrow and spleen assessments)

Disease response assessment

Long-term follow-up subject status date where status = alive

End of treatment disposition where status is not equal to death, lost to follow-up

End of Month 3 disposition where status is not equal to death, lost to follow-up

End of study data where end of study reason is not equal to death, lost to follow-up


KTE-X19
Statistical Analysis Plan
Kite Pharma, Inc.
KTE-C19-102 (ZUMA-2)
Final
CONFIDENTIAL
Page 44
08 July 2019
Appendix 4.
Derivation of Simplified Mantle Cell Lymphoma International 
Prognostic Index
The simplified Mantle Cell Lymphoma International Prognostic Index (s-MIPI) will be derived 
as described in Hoster {Hoster 2008}. 
Table 9.
Simplified Mantle Cell Lymphoma International Prognostic Index
Points
Age, yr
ECOG
LDH, ULN
WBC, 109/L
0
< 50
0 to 1
< 0.67
< 6.700
1
50 to 59
NA
0.67 to 0.99
6.700 to 9.999
2
60 to 69
2 to 4
1.000 to 1.49
10.000 to 14.999
3
≥70
NA
≥1.5000
≥15.000
Abbreviations:  ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; NA, not applicable; ULN, upper 
limit of normal; WBC, white blood count; yr; year.
For each prognostic factor, 0 to 3 points will be given to each subject and points will be summed 
up to a maximum of 11 points. Subjects with 0 to 3 points in summary will be classified as low 
risk, subjects with 4 to 5 points as intermediate risk, and subjects with 6 to 11 points as high risk. 
Eastern Cooperative Oncology Group (ECOG) performance status will be weighted with 2 points 
if subjects are unable to work or bedridden (ECOG 2 to 4). Lactate dehydrogenase (LDH) will 
be weighted according to the ratio to the upper limit of normal. Thus, for an upper limit of 
normal of 240 U/L, the cutpoints will be 180 U/L, 240 U/L, and 360 U/L, for example.
That is, Simplified Mantle Cell Lymphoma International Prognostic Index (s-MIPI) score = sum 
of the points for age, ECOG performance status, LDH, and white blood count from the above 
table. The s-MIPI score can be classified into 3 risk categories as follows.
Table 10.
Risk Category Based on s-MIPI
s-MIPI score
Risk Category
0 to 3
Low risk
4 to 5
Intermediate risk
6 to 11
High risk
Abbreviation:  s-MIPI, simplified Mantle Cell Lymphoma International Prognostic Index.