Clinical trial NCT03624036
Conditions: Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma
Sponsor: Kite, A Gilead Company
Start date: 2018-11-15; Completion date: 2022-11-18
Enrollment: 16 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The primary objective of this study is to evaluate the safety and tolerability of brexucabtagene autoleucel (KTE-X19) in adults with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and small lymphocytic lymphoma (r/r SLL) who have received at least 2 prior lines of treatment, one of which must include a Bruton's tyrosine kinase (BTK) inhibitor.

After the end of KTE-C19-108, participants who received an infusion of brexucabtagene autoleucel will complete the remainder of the 15-year follow-up assessments in a separate Long-term Follow-up study, KT-US-982-5968 (NCT05041309).

Detailed description:

Arms: arm 1: Participants with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) will receive conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg on Day 0. arm 2: Participants with r/r CLL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0. arm 3: Participants with r/r CLL and small lymphocytic lymphoma (SLL) with ≤1% malignant cells in peripheral blood or absolute lymphocyte count (ALC) \< 5,000 cells/μL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg on Day 0. arm 4: Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, B-cell lymphoma 2 (BCL-2) and Phosphoinositide 3-kinase (PI3k) inhibitors will receive ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg on Day 0. arm 5: Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, BCL-2 and PI3k inhibitors will receive ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Upon completion of Cohort 4A, it was determined not to enroll participants in Cohort 4B.
Interventions: intervention 1: brexucabtagene autoleucel intervention 2: Fludarabine intervention 3: Cyclophosphamide
Intervention descriptions: intervention 1: CAR-transduced autologous T cells administered intravenously intervention 2: Administered intravenously intervention 3: Administered intravenously

Protocol documents:
SAP_002.pdf: 
  
TRANSLATIONAL STATISTICAL ANALYSIS PLAN KTE-C19-108
TRANSLATIONAL ANALYSIS 
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Product Name:
KTE-X19
Protocol Title:
A Phase 1 Multicenter Study Evaluating the Safety and 
Tolerability of KTE-X19 in Adult Subjects with 
Relapsed/Refractory Chronic Lymphocytic Leukemia and 
Small Lymphocytic Lymphoma 
Protocol Number
KTE-C19-108 (ZUMA-8)
Version Number:
Version 1.05
Release Date:
24 September 2021
Replaces Previous 
Version(s):
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, 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.  Questions 
regarding how this document should be used or the conduct of the clinical trial should be 
directed to the key sponsor contacts.
 
 
 


KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
Page 2
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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF TABLES..........................................................................................................................................................2
LIST OF ABBREVIATIONS.........................................................................................................................................3
1.
INTRODUCTION..................................................................................................................................................4
2.
OBJECTIVES.........................................................................................................................................................5
2.1.
Objectives..................................................................................................................................................5
2.2.
Hypothesis .................................................................................................................................................5
3.
ENDPOINTS, SUBGROUPS AND COVARIATES ............................................................................................6
3.1.
Datasets to be Included..............................................................................................................................6
3.2.
Endpoints...................................................................................................................................................7
3.3.
Outcomes, Subgroups, and Covariates......................................................................................................7
4.
DEFINITIONS .......................................................................................................................................................8
4.1.
General ......................................................................................................................................................8
4.2.
Key Measurements of Anti-CD19 CAR+ T Cell ......................................................................................8
4.3.
Key Measurements of Serum Cytokines ...................................................................................................9
4.4.
Key Measurements of Product Characteristics..........................................................................................9
5.
ANALYSIS SETS................................................................................................................................................10
6.
STATISTICAL ANALYSIS................................................................................................................................11
6.1.
General Methods .....................................................................................................................................11
6.2.
Analysis ...................................................................................................................................................11
6.2.1.
Characterize the anti-CD19 CAR T Cell Expansion (PK) and Serum 
Cytokine Profile ....................................................................................................................11
6.2.2.
Characterize Product Attributes ............................................................................................11
6.2.3.
Explore MRD negativity .......................................................................................................11
7.
APPENDIX ..........................................................................................................................................................12
7.1.
Definition of Analytic Visit Windows for CAR T Cells in Blood..........................................................12
7.2.
Definition of Analytic Visit Windows for Cytokines in Serum..............................................................12
7.3.
Using Trapezoidal Rule to Approximate the Area under the Curve (AUC) ...........................................13
LIST OF TABLES
Table 3-1.
Data Overview on Assay Methods and Biomarker Lists...........................................................6
Table 7-1.
Analytic Visit Windows for CAR T Cells in Blood................................................................12
Table 7-2.
Analytic Visit Windows for Cytokines in Serum....................................................................12


KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
Page 3
23 August 2021
LIST OF ABBREVIATIONS
AUC
Area under the curve
CAR
Chimeric antigen receptor
CD
Cluster of differentiation
CRP
C-reactive protein
CRS
Cytokine release syndrome
CXCL
C-X-C motif chemokine ligand
ddPCR
Droplet digital polymerase chain reaction 
DLT
Dose-limiting toxicity
DNA
Deoxyribonucleic acid
ICAM
Intercellular adhesion molecule
IFN
Interferon
IL
Interleukin
LOQ
Limit of quantification
LYMLE
Lymphocyte (%)
MONOLE
Monocyte (%)
MRD
Minimal residual disease
MTD
Maximum toxicity dose
PBMC
Peripheral blood mononuclear cells
PD
Pharmacodynamics
PK
Pharmacokinetic
SAP
Statistical analysis plan
TNF
Tumor necrosis factor
TSAP
Translational statistical analysis plan
VCAM
Vascular cell adhesion molecule
WBC
White blood cell count


KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
Page 4
23 August 2021
1.
INTRODUCTION
This translational statistical analysis plan (TSAP) outlines the analyses to be conducted for 
pharmacokinetics (PK) (levels of anti-CD19 CAR T cells), pharmacodynamics (levels of 
cytokines and other key analytes) and product characteristics data for Study KTE-C19-108 
(ZUMA-8) titled “A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of 
KTE-X19 in Adult Subjects with Relapsed/Refractory Chronic Lymphocytic Leukemia and 
Small Lymphocytic Lymphoma”, as described in protocol amendment 3 dated 01 September 
2021.


KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
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2.
OBJECTIVES
2.1.
Objectives

Characterize the anti-CD19 CAR T cell expansion (PK) 

Characterize profile for selected serum cytokines (PD) 

Characterize the product characteristics

Characterize Minimal Residual Disease (MRD) data for bone marrow and peripheral blood 
samples
2.2.
Hypothesis
The analyses outlined in this TSAP are 
and no formal pre-specified hypothesis will 
be tested.
CCI




KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
Page 7
23 August 2021
3.2.
Endpoints

Levels of anti-CD19 CAR T cells in blood samples measured as anti-CD19 CAR+ cells/µL 
by visit, peak, area under the curve (AUC) (from infusion to Day 28), and time-to-peak 
(details for the derivations are included in the definition Section 4.2)

Levels of cytokines in serum by visit, change from baseline at Day 0, Day 1, Day 4 and 
Day 7, fold change from baseline at Day 0, Day 1, Day 4 and Day 7, peak, Day 0 – Day 28 
AUC, and time to peak (details for the derivations are included in the definition Section 4.3)

Product attributes measurements after product manufacturing and prior to dosing

Levels of CLL of nucleated cells and of CD45+Lymphocytes by visit, Screening, Bridging 
Chemotherapy, Day 28, Month 3
3.3.
Outcomes, Subgroups, and Covariates
No outcomes, subgroups and covariates will be used for analyses in this TSAP. 


KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
Page 8
23 August 2021
4.
DEFINITIONS
4.1.
General
Study Day 0: defined as the day the subject received the first KTE-X19 infusion.
Baseline: the baseline value is defined as the last value taken prior to first dose of conditioning 
chemotherapy. If the enrolled subjects do not receive conditioning chemotherapy, the baseline 
value is defined as the last value taken prior to enrollment/leukapheresis.
4.2.
Key Measurements of Anti-CD19 CAR+ T Cell 
The presence, expansion, and persistence of anti-CD19 CAR T cells in peripheral blood will be 
measured by ddPCR analysis. 
Scheduled blood draw for anti-CD19 CAR T cell: This TSAP will focus on the anti-CD19 
CAR T cell data collected as per planned assessment,  based on the analysis visits defined in 
Appendix Section 7.1.
Baseline number of anti-CD19 CAR T cells (cells/ µL) is defined as 0 before the KTE-X19 
infusion on Day 0, and number of CAR T (cell/µL) will not be derived. 
Number of anti-CD19 CAR T (cells/ µL) derivation:
Derivation 1

Alpha = (CAR /µg DNA at timepoint) / 162,000 

Beta = (CAR /µg DNA of product / 162,000) / % Transduction (by flow of product)

Optimized % CAR+ PBMC = (Alpha/Beta) 

Number of anti-CD19 CAR T (cells/µL blood) is defined as:
1000*(WBC [10^9/L])*(MONOLE [%] + LYMLE [%])/100*Optimized %CAR+PBMC
Peak of anti-CD19 CAR T cell (cells/ µL blood) is defined as the maximum absolute number 
of anti-CD19 CAR T (cells/ µL) in serum attained after Day 0.
Time to Peak of anti-CD19 CAR T cell is defined as the number of days from Day 0 to the day 
when the peak of anti-CD 19 CAR T cell was attained as “Peak date – KTE-X19 Dosing date + 1.”
Area-Under-Curve (AUC) of level of anti-CD19 CAR T cell (cells/µL ▪ days) from Day 0 to 
Day 28 is defined as the AUC in a plot of levels of anti-CD19 CAR T cells against scheduled 
visits from Day 0 to Day 28. This AUC measures the total levels of anti-CD19 CAR T cells over 
time. Given the anti-CD19 CAR T cells are measured at certain discrete time points, the 
trapezoidal rule will be used to estimate the AUCs. 




KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
Page 10
23 August 2021
5.
ANALYSIS SETS
Translational analysis will use the analysis sets defined in clinical SAP unless otherwise 
specified. The following subjects will be involved in analysis:

Safety Analysis Set
The safety analysis set is defined as all subjects treated with any dose of KTE-X19. The 
safety analysis set will be the primary analysis set used to summarize the translational data in 
this TSAP.




KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
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7.
APPENDIX
 
 
CCI


KTE-X19
Translational Statistical Analysis Plan
KTE-C19-108 (ZUMA-8)
Kite Pharma, Inc.
CONFIDENTIAL
Page 13
23 August 2021
7.3.
Using Trapezoidal Rule to Approximate the Area under the Curve (AUC)
AUC ≈1
2(𝑦0 + 𝑦1) ∙Δ𝑥+ 1
2(𝑦1 + 𝑦2) ∙Δ𝑥+ 1
2(𝑦2 + 𝑦3) ∙Δ𝑥+ …
 
 
 
 
 
 

Prot_000.pdf: 
Protocol Title: 
Protocol Number: 
USAN/INN: 
Company Code: 
IND Number: 
EudraCT Number: 
Clinical Study Sponsor: 
Key Sponsor Contacts: 
Protocol Version/Date: 
CLINICAL STUDY PROTOCOL 
A Phase 1 Multicenter Study Evaluating the Safety and 
Tolerability of KTE-X19 in Adult Subjects with 
Relapsed/Refracto1y Chronic Lymphocytic Leukemia and 
Small L ymphocytic Lymphoma 
KTE-C19-108 (ZUMA-8) 
Brexucabtagene Autoleucel/TBD 
KTE-X19 
16675 
2018-001923-38 
Kite Phanna, Inc. 
2400 Broadway 
Santa Monica, CA 90404 
r 
e ical Director, Clinical Development 
Pho 
PD 
D 
Clinical Program Manager, Clinical Operations 
Phone: PD 
Email PD 
Original 
Amendment 1 
Amendment2 
Amendment3 
15 June 2018 
02 May 2019 
27 May2020 
01 September 2021 
CONFIDENTIALITY STATEMENT 
This document contains confidential info1mation of Kite Phaim a, Inc., a wholly owned 
subsidiaiy of Gilead Sciences Inc. This document must not be disclosed to anyone other than 
the site research staff, collaborators, and members of the Institutional Review 
Boai·d/Independent Ethics Committee, a scientific review board, or an equivalent. The 
info1mation in this document cannot be used for any pmpose other than the conduct of the 
clinical investigation without the prior written consent of Kite Phaim a, 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-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 2
01 September 2021
PROTOCOL SYNOPSIS
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
Title:
A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of 
KTE-X19 in Adult Subjects with Relapsed/Refractory Chronic 
Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Indication:
Adult subjects with relapsed or refractory (r/r) chronic lymphocytic 
leukemia (CLL) and r/r small lymphocytic lymphoma (SLL) who 
have been previously treated with at least two prior lines of therapy, at 
least one of which must have included any Bruton’s tyrosine kinase 
(BTK) inhibitor
Study Design:
ZUMA-8 is a Phase 1, multicenter, open-label study evaluating the 
safety and tolerability of KTE-X19 in adult subjects with r/r CLL and 
SLL.
During the study, approximately 15 to 27  subjects with r/r CLL and 
SLL will be assessed to evaluate the safety of KTE-X19. A safety 
review team (SRT) that is internal to the study sponsor, in 
collaboration with at least 1 study investigator, will review all data 
available, including safety and efficacy data and make 
recommendations regarding further enrollment based on the incidence 
of dose-limiting toxicities (DLTs) and overall safety profile and cell 
expansion of KTE-X19. See Section 9.7.
The trial will separated into two different stages:
In the first stage, subjects with r/r CLL will be enrolled using a 6+3 
study design into cohorts described below:

Cohort 1: Up to 9 subjects will be enrolled at 1 x 106 anti-CD19 
chimeric antigen receptor (CAR) T cells/kg. Decision to enroll in 
Cohort 2 will be based on incidence of DLT in Cohort 1.

Cohort 2: Up to 9 subjects will be enrolled at 2 x 106 anti-CD19 
CAR T cells/kg. In the second stage (Amendment 2), subjects with 
r/r CLL and SLL will be enrolled into Cohort 3 and 4 as described 
below: 

Cohort 3: Three (3) subjects with r/r CLL andSLL with ≤ 1% 
malignant cells in peripheral blood or absolute lymphocyte count 
(ALC) < 5,000 cells/μL will be enrolled and dosed with KTE-X19 
at a dose of 1 x 106 anti-CD19 CAR T cells/kg. Subjects must 
have received at least 2 prior lines of treatment, one of which must 
include a BTK inhibitor. This is an exploratory cohort. No 
additional dose levels will be evaluated.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 3
01 September 2021

Cohort 4: Up to approximately 15 subjects with r/r CLL who have 
been previously treated with at least two prior lines of therapy and 
are receiving ibrutinib as a single agent, or ibrutinib in 
combination with anti-CD20 antibodies, BCL-2 inhibitors, and 
PI3k inhibitors as the last line of therapy. Subjects must have 
received ibrutinib for at least 6 months prior to screening. Ibrutinib 
administration will continue up to 30 hours prior to leukapheresis. 
In case of treatment interruption with ibrutinib, the principal 
investigator should reach out to the medical monitor to discuss. 
A 3+3 study approach will be used to evaluate two doses of 
KTE-X19.
Cohort 4A: 
■
Up to 6 subjects using 3+3 approach will be enrolled and 
dosed at 1 x 106 anti-CD19 chimeric antigen receptor 
(CAR) T cells/kg. Decision to enroll in Cohort 4B will be 
based on SRT review of Cohort 4A.
*Upon completion of Cohort 4A SRT, it was determined not to 
enroll subjects in Cohort 4B. 
Cohort 4B:  
■
Up to 12 subjects will be enrolled and dosed at 2 x 106 
anti-CD19 chimeric antigen receptor (CAR) T cells/kg.
Once a safe dose is established in Cohort 4, additional subjects will be 
enrolled and dosed for a total of up to twelve (12) subjects at the safe 
dose level. The maximum number of subjects enrolled and dosed in 
Cohort 4 will be approximately 15 subjects. 
Each subject will proceed through the following study periods:

Screening 

Enrollment/Leukapheresis 
 

Lymphodepleting/Conditioning chemotherapy 

Investigational product (IP) treatment 

Post-treatment assessment 

Long-term follow-up 
For study requirements assigned to each study arm, refer to the 
schedule of assessments (SOA) and Section 7 for details.
A study schema is provided at the end of the protocol synopsis 
section.
CCI


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
Study Objectives: 
Hypothesis: 
Primary Endpoints: 
Secondary 
Endpoint(s): 
Sample Size: 
Study Eligibility: 
Treatment: 
CONFIDENTIAL 
Primaiy objective of Phase 1: Evaluate the safety and tolerability of 
KTE-X19 in subjects with r/r CLL and SLL. 
Secondaiy objectives ai·e to chai·acterize the safety profile and anti-
KTE-X19 antibody, and to evaluate the efficacy of KTE-X19 as 
measured by the objective response rate (ORR) per investigator 
review in subjects with r/r CLL treated with KTE-X19. Efficacy 
analysis for ORR will be perfo1m ed only for the selected safe dose 
cohort. 
No fo1m al hypothesis testing for this phase 1 study. 
Incidence of DLTs in subjects treated with KTE-X19 (Section 9.7) 
• 
ORR (CR/CRi/PR) per investigator review as defined by 
IWCLL 2018 criteria (Appendix 3) for selected safe dose coho1i 
• 
Incidence of adverse events (AEs) 
• 
Levels of anti-CD19 CART cells in blood 
Up to approximately 27 subjects will be enrolled and treated in the 
study. 
See Section 5 for list of all eligibility criteria. 
All subjects will receive conditionin 
investigational treatment, KTE-X19. 
Conditioning Chemotherapy 
KTE-X19 is administered after a conditioning chemotherapy regimen 
consisting of fludarabine 30 mg/m2/day and cyclophosphamide 
500 mg/m2/day administered IV over 30 minutes on Day - 5, Day - 4, 
and Day - 3 prior to KTE-X 19 infusion. Day - 2 and Day - 1 are rest 
days. 
Page4 
01 September 2021 


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
Procedures: 
CONFIDENTIAL 
KTE-X19 
KTE-X19 treatment consists of a single infusion of CAR-trnnsduced 
autologous T cells administered intrnvenously (IV) at a target dose of 
1 x 106 or 2 x 106 anti-CD19 CART cells/kg (Section 3.1). 
All subjects will be hospitalized to receive KTE-X19 infusion 
followed by a minimum 7-day observation period. 
Refer to Section 6.1.4 and Section 7.9.3.2 for ti·eatment details. 
Refer to Section 6 .1. 3 and Section 7. 9. 3 for chemotherapy ti·eatment 
details. 
At specific time points as outlined in the SOA, subjects will undergo 
the following procedmes: collection of info1med consent; general 
medical histo1y, including previous treatments for CLL and SLL; 
physical exam, including vital signs and Eastern Cooperative 
Oncology Group (ECOG) perfonnance status; local blood draws for 
complete blood count (CBC), chemistry panels, lactate dehydrogenase 
(LDH), C-reactive protein, feITitin; central blood draws for cytokines, 
lymphocyte subsets, antibodies to anti-CD19 CART cells, 
replication-competent-reti·oviI11s (RCR), and anti-CD19 CAR T cell 
analysis. Women of childbearing potential will undergo a mine or 
sernm pregnancy test. 
Page5 
01 September 2021 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 6
01 September 2021
Subjects will also undergo a baseline electrocardiogram (ECG), 
echocardiogram (ECHO/MUGA), diagnostic computed 
tomography(CT) scan (preferred) or magnetic resonance imaging 
(MRI) of the head, neck, chest, abdomen, and pelvis, bone marrow 
aspirate and biopsy, 
 and leukapheresis. 
Routinely throughout the conduct of the study, all subjects will be 
asked to report concomitant therapies, AEs, and subsequent CLL 
andSLL therapy.  Subjects will undergo neurological assessment.  
For details for all study requirements, refer to Section 7 and the SOAs.
Statistical 
Considerations:
The primary endpoint for the Phase 1 portion of the study is incidence 
of DLTs in subjects treated with KTE-X19.  A 6 + 3 dose 
escalation/de-escalation plan was used in the Cohort 1 and Cohort 2 
DLT evaluation period.  Amendment 2 will use a 3 + 3 dose escalation 
plan for Cohort 4.  Cohort 3 is an exploratory cohort. 
For the selected safe dose cohort, the ORR (CR/CRi/PR) will be 
calculated for mITT analysis set. A 95% confidence interval will be 
provided by Clopper-Pearson method. The mITT set is defined as all 
subjects treated with KTE-X19 and with radiographically measurable 
disease 
 prior 
to administration of conditioning chemotherapy.
CCI
CCI


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
Figure 1. 
Study Schema 
Investii:ational Treatment 
KTE-X19 Treatment Pel'iod 
f/l 
illll.fil 
"' 
..0 
• ;;j 
.... 
-0 
Conditionin& Chemothern)!v 
s::: 
0 
Cl) 
Subject is hospitalized prior to 
Cl) 
·c:: 
(Day -5 to -3) 
s 
Cl) 
...c: 
tl'eatment with KTE-X19 and 
"' 
p... 
0. 
"' 
0., 
remains hospitalized for 
Cl) 
on 
Fludarabine 30 mg/m2/day 
"' 
;::, 
"' 
I 
.!: 
:::l 
Cyclophosphamide 
observation for a minimum of 
<I:'. 
5 
Cl) 
7 days after tl'eatment 
.... 
..9 
__,. 
__,. 
500mg/m2/day 
__,. 
s::: __,. 
0 
Cl) 
----
X 3 days 
Cl) 
!3 
.... 
KTE-X19 at the defined dose per 
.s 
µ.. 
r/) 
C: 
(Day -5 to Day -3; 
§ 
Cl) 
the specific Coho1t 
ro 
Cl) 
.§ 
Day -2 and Day-I are rest 
Cl) 
0 
days) 
I 
r' 
.... 
00 
"' 
s::: 
0 
p... 
0 
p:,l 
....:l 
b 
After the end of KTE-C 19-108, subjects who received an infusion of KTE-X19 will complete the remainder of the 15-year follow-up assessments in a separate long-te1m 
follow-up study, KT-US-982-5968. 
CONFIDENTIAL 
Page7 
01 September 2021 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 8
01 September 2021
TABLE OF CONTENTS
PROTOCOL SYNOPSIS................................................................................................................................................2
TABLE OF CONTENTS................................................................................................................................................8
LIST OF TABLES........................................................................................................................................................10
LIST OF FIGURES ......................................................................................................................................................10
LIST OF ABBREVIATIONS.......................................................................................................................................11
1.
OBJECTIVES.......................................................................................................................................................13
1.1.
Primary Objective....................................................................................................................................13
1.2.
Secondary Objectives ..............................................................................................................................13
2.
DISEASE BACKGROUND ................................................................................................................................14
2.1.
CLL and SLL Disease Background.........................................................................................................14
2.2.
KTE-X19 .................................................................................................................................................17
2.3.
Prior Anti-CD19 CAR T-cell Study Designs and Results.......................................................................17
3.
STUDY DESIGN AND RATIONALE................................................................................................................18
3.1.
General Study Design..............................................................................................................................18
3.2.
Study Rationale For Cohort 1 and Cohort 2............................................................................................20
3.2.1.
Rationale for Cohort 3...........................................................................................................20
3.2.2.
Rationale for Cohort 4 {Geyer 2019} ...................................................................................21
3.2.3.
Rationale for Conditioning Chemotherapy ...........................................................................23
3.2.4.
Rationale for KTE-X19 Dose................................................................................................23
3.3.
Overall Risk and Benefit Assessment .....................................................................................................23
3.4.
Participating Sites....................................................................................................................................24
3.5.
Number of Subjects .................................................................................................................................24
3.6.
Replacement of Subjects .........................................................................................................................25
3.7.
Study Duration.........................................................................................................................................25
3.7.1.
Study Duration for Individual Subjects.................................................................................25
3.7.2.
Completion of Study..............................................................................................................25
3.7.3.
Long-term Follow-up ............................................................................................................25
4.
SUBJECT IDENTIFICATION ASSIGNMENT .................................................................................................26
5.
SUBJECT ELIGIBILITY.....................................................................................................................................27
5.1.
Inclusion Criteria.....................................................................................................................................27
5.2.
Exclusion Criteria....................................................................................................................................28
6.
PROTOCOL TREATMENT................................................................................................................................31
6.1.
Study Treatment ......................................................................................................................................31
6.1.1.
Leukapheresis........................................................................................................................31
6.1.3.
Conditioning Chemotherapy .................................................................................................31
6.1.4.
KTE-X19 ...............................................................................................................................32
6.2.
Concomitant Therapy ..............................................................................................................................33
6.3.
Excluded Medications .............................................................................................................................33
6.4.
Subsequent Therapy ................................................................................................................................34
7.
STUDY PROCEDURES......................................................................................................................................35
7.1.
Informed Consent ....................................................................................................................................35
7.2.
Screening .................................................................................................................................................35
CCI
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7.2.1. 
Rescreening ........................................................................................................................... 36 
7.3. 
De1nographic Data ................................................................................................................................... 36 
7.4. 
Medical and Treatment Histoiy ............................................................................................................... 36 
7.5. 
Physical Exam, Vital Signs, and Pe1formance Status ............................................................................. 36 
7.6. 
Cardiac Function ..................................................................................................................................... 37 
7.7. 
Neurological Exainination ....................................................................................................................... 37 
7.8. 
Disease Assessment ................................................................................................................................. 37 
7 .8.1. 
Radiology Assessment. .......................................................................................................... 37 
7.8.2. 
Bone Mall'ow Assessment ..................................................................................................... 38 
7.9. 
Cell Collection and Study Treatment Schedule and Administration ....................................................... 39 
7.9.1. 
Leuka heresis ........................................................................................................................ 39 
-
7.9.3. 
Conditioning Chemotherapy and KTE-Xl9 Infusion .......................................................... .40 
7.9.4. 
Requirements to Work-up Potential Infectious and/or Inflammato1y States ........................ 44 
7 .10. 
Toxicity Manage1nent ............................................................................................................................. .45 
7 .11. 
Laborato1y .............................................................................................................................................. .45 
7 .11.1. 
Local Lab Analysis ............................................................................................................... .45 
7.11.2. 
Central Laborato1y Analyses ................................................................................................ .46 
7 .12. 
Post-treatment Assessment Period ......................................................................................................... .48 
7.13. 
Long-te1m Follow-up Period .................................................................................................................. .49 
7.14. 
Schedule of Assessinents ......................................................................................................................... 51 
8. 
SUBJECT WITHDRAW AL ................................................................................................................................ 56 
8.1. 
Reasons for Re1noval from Treatinent .................................................................................................... 56 
8.2. 
Reasons for Re1noval from Study ............................................................................................................ 57 
9. 
SAFETY REPORTING ........................................................................................................................................ 58 
9.1. 
Definition of Adverse Events .................................................................................................................. 58 
9.1.1. 
Diagnosis Versus Signs and Symptoms ................................................................................ 58 
9.1.2. 
Abno1mal Vital Sign Values ................................................................................................. 59 
9 .1.3. 
Reporting Abno1mal Laborat01y Findings ............................................................................ 59 
9.2. 
Reporting of Adverse Events ................................................................................................................... 59 
9.3. 
Definition of Serious Adverse Events ..................................................................................................... 61 
9 .3 .1. 
Hospitalization and Prolonged Hospitalization ..................................................................... 61 
9.4. 
Reporting of Serious Adverse Events ...................................................................................................... 62 
9.5. 
Reporting Deaths ..................................................................................................................................... 63 
9.6. 
Pregnancy and Lactation ......................................................................................................................... 63 
9.7. 
Safety Review Team and Dose-limiting Toxicity ................................................................................... 64 
9.8. 
Criteria to Pause Enroll1nent ................................................................................................................... 67 
10. STATISTICAL CONSIDERATIONS ................................................................................................................. 68 
10.1. 
Hypothesis ............................................................................................................................................... 68 
10.2. 
Study Endpoints ....................................................................................................................................... 68 
10.2.1. 
Pri1naiy Endpoints ................................................................................................................. 68 
10.2.2. 
Secondai End oints ............................................................................................................. 68 
1111 
10.3. 
Sample Size Considerations .................................................................................................................... 69 
10.4. 
Access to Individual Subject Treatment Assignments ............................................................................ 69 
10.5. 
Interim Analysis and Early Stopping Guidelines .................................................................................... 70 
10.6. 
Analysis Subsets ...................................................................................................................................... 70 
10.7. 
Planned Method of Analysis ................................................................................................................... 70 
10.7.1. 
ORR ....................................................................................................................................... 70 
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10.7.8. 
Safety ..................................................................................................................................... 71 
11. REGULATORY OBLIGATIONS ....................................................................................................................... 72 
11.1. 
Independent Review Board/Independent Ethics Committee ................................................................... 72 
11.2. 
Subject Confidentiality ............................................................................................................................ 72 
11.3. 
Investigator Signato1y Obligations .......................................................................................................... 73 
12. PROTOCOL AMENDMENTS AND TERMINATION ..................................................................................... 74 
13. STUDY DOCUMENTATION AND ARCHIVING ............................................................................................ 75 
14. STUDY MONITORING AND DATA COLLECTION ...................................................................................... 76 
15. PUBLICATION ................................................................................................................................................... 77 
16. COMPENSATION ............................................................................................................................................... 78 
17. REFERENCES ..................................................................................................................................................... 79 
18. APPENDICES ...................................................................................................................................................... 85 
Appendix 1. 
Appendix 2. 
Appendix 3. 
Appendix 4. 
Appendix 5. 
Table 1. 
Table 2. 
Table 3. 
Table 4. 
Table 5. 
Table 6. 
Table 7. 
Table 8. 
Table 9. 
Figure 1. 
CONFIDENTIAL 
Sponsor and Investigator Signature Page ................................................................................ 86 
Binet and Rai Staging Systems for the Classification of CLL ................................................ 87 
IWCLL 2018 Response Criteria and Disease Response Assessment.. .................................... 88 
Countiy specific regulato1y agency requirements ................................................................... 90 
Birth control methods which may be considered as highly effective1 ..................................... 91 
LIST OF TABLES 
Repo1t ing Requirements for Concomitant Medications .......................................................... 33 
Clinical Laborato1y Paraineters .............................................................................................. .45 
Schedule of Assessments ......................................................................................................... 51 
Long-tenn Follow-up Assessments ......................................................................................... 53 
Repo1t ing Requirements for Adverse Events .......................................................................... 60 
Repo1t ing Requirements for Serious Adverse Events ............................................................. 62 
DLT Criteria ............................................................................................................................ 65 
DLT Evaluation Cohort 1 and Coho11 2 .................................................................................. 66 
DLT Evaluation Cohort 4 ........................................................................................................ 66 
LIST OF FIGURES 
Study Schema ............................................................................................................................ 7 
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LIST OF ABBREVIATIONS 
AE
Adverse event
ALC
Absolute lymphocyte count
BCL-2
B-cell lymphoma 2 
BR
Bendamustine and rituximab
BTK
Bruton’s tryrosine kinase 
CAR
Chimeric antigen receptor 
CBC
Complete blood count
CLL
Chronic lymphocytic leukemia
CNS
Central nervous system
CR
Complete response
CRF
Case report form
CRi
Complete response with incomplete hematopoetic recovery
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
DLT
Dose-limiting toxicity
ECHO
Echocardiogram
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EU
European Union
FAS
Full analysis set
FCR
Fludarabine cyclophosphamide, and rituximab
GCP
Good Clinical Practice
GVHD
Graft-versus-host disease
HEENT
Head, ears, eyes, nose, and throat
HLH
Hemophagocytic lymphohistiocytosis
HIV
Human immunodeficiency virus
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Hamonisation of Technical Requirements for 
Pharmaceuticals for Human Use
IP
Investigational product
IPM
Investigational Product Manual
IRB/IEC
Institutional Review Board/Endependent Ethics Committee
ITK
IL-2-inducible T-cell kinase
IV
Intravenous


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IWCLL
International Workshop on Chronic Lymphocytic Leukemia
KI
Kinase inhibitor
LP
Lumbar puncture
LVEF
Left ventricular ejection fraction
LTFU
mITT
Long-term Follow-up 
Modified intend to treat
MRI
Magnetic resonance imaging
MRD
Minimal residual disease
NCI
National Cancer Institute
OS
Overall survival
ORR
Objective response rate
PBMC
Peripheral blood mononuclear cells
PD
Progressive disease
PFS
Progression-free survival
PI-3K
Phosphoinositide 3-kinase inhibitor
PK
Pharmacokinetic(s)
PR
Partial response
r/r
Relapsed/refractory
RCR
Replication-competent retrovirus
SAE
Serious adverse event
scFv
Single chain variable fragment
SCT
Stem cell transplant
SLL
Small lymphocytic lymphoma
SOA
Schedule of assessments
SOC
Standard of care
SRT
Safety review team
TEAEs
Treatment emergent adverse events
Tcm
Central memory T cells
Treg
Regulatory T cells
WBC
White blood cell


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
L 
OBJECTIVES 
1.1. 
Primary Objective 
The prima1y objective of the study is to evaluate the safety and tolerability of KTE-X19 in 
subjects with relapsed or refracto1y (r/r) chronic lymphocytic leukemia (CLL) and small 
lymphocytic lymphoma (SLL). 
1.2. 
Secondary Objectives 
Secondaiy objectives ai·e to characterize the safety profile and anti-KTE-X19 antibodies, and to 
evaluate the efficacy of KTE-X19 as measmed by the objective response rate (ORR) per 
investigator review in subjects with r/r CLL treated with KTE-X19. Efficacy analysis for ORR 
will be perfo1med only for the selected safe dose cohort. 
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2.
DISEASE BACKGROUND 
2.1.
CLL and SLL Disease Background
CLL is the most commonly occurring leukemia in Europe and the United States (US) with an 
estimated lifetime risk of 1:167 {Sant 2010, Surveillance Epidemiology and End Results (SEER) 
Program 2011}. CLL is marked by the progressive accumulation of functionally impaired 
monoclonal B lymphocytes in blood, bone marrow, lymph nodes, spleen, and liver {Hallek 2018, 
Rozman 1995}. Symptoms include fever, night sweats, and weight loss, and disease progression 
is often accompanied by lymphadenopathy, splenomegaly, or hepatomegaly. CLL is most 
commonly a disease of the elderly, as 70% of patients are ≥ 65 years at diagnosis, and the 
median age is 72 years {Surveillance Epidemiology and End Results (SEER) Program 2011}. 
Patients harboring a deletion of the short arm of chromosome 17 (del17p) or an inactivating 
mutation in the TP53 gene (TP53mut) are considered to be high-risk and have worse survival 
outcomes than patients who do not harbor these mutations {Hallek 2019}.
CLL and small lymphocytic lymphoma (SLL) are different manifestations of the same disease. 
SLL are the less frequent nonleukemic cases of CLL, where lymph node involvement is 
prevalent, in the absence of cytopenias caused by a clonal bone marrow infiltrate, and with 
< 5 x 109/L B lymphocytes in the peripheral blood {Tsimberidou 2007}. The diagnosis of SLL 
requires the presence of lymphadenopathy and/or splenomegaly with < 5 x 109/L B lymphocytes 
in the peripheral blood. In SLL, the diagnosis should be confirmed by histopathology evaluation 
of a lymph node biopsy. SLL follows the same management guidelines as CLL {Scarfo 2016}. 
The indolent clinical behavior of SLL has often led to the approach of deferring treatment in 
asymptomatic patients until progressive disease (PD) becomes evident.
For the treatment of CLL and SLL, chemoimmunotherapy remains an option, particularly as an 
initial treatment, for those who are considered to be fit and of favorable-risk.  The CLL8 and 
CLL10 studies of the German CLL group established the benefit of adding an anti-CD20 
monoclonal antibody to chemotherapy and the value of the fludarabine, cyclophosphamide, and 
rituximab (FCR) and bendamustine and rituximab (BR) regimens for the treatment of CLL 
{Eichhorst 2016, Hallek 2010}. The CLL11 study subsequently demonstrated improved 
outcomes with the third generation anti-CD20 antibody obinutuzumab in combination with 
chlorambucil compared with rituximab-chlorambucil and chlorambucil monotherapy {Goede 
2014}. For the overwhelming majority of patients, these treatments are not curative; the disease 
eventually relapses, necessitating further intervention to establish and maintain tumor control. 
While chemoimmunotherapy can be pursued at the time of relapse, it is associated with toxicity, 
including myelosuppression and fatigue. Patients who relapse after an initial remission duration 
≥ 3 years after frontline FCR are considered suitable to receive FCR again as the first salvage 
therapy. Salvage treatment offers limited benefit for patients with a limited depth of response to 
initial therapy or those who have recurrent disease within 3 years {Tam 2014}. Patients with 
del17p or TP53mut are particularly poorly served by chemoimmunotherapy irrespective of 
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Small molecule targeted agents have transformed the treatment landscape for CLL, largely 
supplanting chemoimmunotherapy, but these agents require chronic administration. One such 
agent is ibrutinib, a first-in-class irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that is 
approved for the treatment of both previously untreated and r/r CLL. In the r/r setting, it results 
in a high objective response rate (ORR) (> 80%) when used in combination with a BR regimen, 
but a limited depth of response (< 22% CR/CRi) {Chanan-Khan 2016}. Among those who 
progress on ibrutinib, a significant proportion of patients develop high-risk disease and have poor 
OS ranging from 3 to 6 months following relapse {Jain 2015, Parikh 2015, Sandoval-Sus 2015}.
A second BTK inhibitor, acalabrutinib, was shown to be efficacious in a Phase 1/2 study of 
132 subjects with r/r CLL (2 additional subjects had SLL). After a median follow-up of 
19.8 months, the ORR was 85% (93% when including partial response [PR] with 
lymphocytosis), but the CR rate was 2%. The median PFS and OS were not reached {Byrd 
2017}. Acalabrutinib has also shown some promise as a treatment for patients with CLL who are 
intolerant to ibrutinib and have not yet progressed {Awan 2016}. This treatment would not be 
suitable for patients who have progressed on ibrutinib or developed BTK mutations. 
Acalabrutinib has been approved for the treatment of adults with CLL as first line therapy as well 
as in the r/r setting, based on 2 randomized, actively controlled trials (ELEVATE-TN and 
ASCEND trials) {CALQUENCE 2019}.
Venetoclax is a first-in-class inhibitor of BCL-2 that is approved for patients with r/r CLL who 
have del17p and at least 1 prior therapy in the US. Venetoclax was also approved by the FDA in 
May 2019 for first line treatment for adult patients with CLL or SLL {VENCLEXTA 2019}. 
Approval was based on CLL14 (NCT02242942), a randomized (1:1), multicenter, open label, 
actively controlled trial of venetoclax in combination with obinutuzumab (VEN +G) versus 
obinutuzumab in combination with chlorambucil (GClb) in 432 patients with previously 
untreated CLL with coexisting medical condition. The major efficacy outcome was progression-
free survival (PFS) assessed by an independent review committee. The trial demonstrated a 
statistically significant improvement in PFS for patients who received VEN+G compared with 
those who received GClb (HR 0.33; 95% CI: 0.22, 0.51; p<0.0001). Median PFS was not 
reached in either arm after a median follow-up duration of 28 months. The overall response rate 
was 85% in VEN+G arm compared to 71% in GClb arm, p=0.0007. The trial also demonstrated 
statistically significant improvements in rates of minimal residual disease negativity (less than 
one CLL cell per 104 leukocytes) in bone marrow and peripheral blood. Overall survival data 
were not mature at this analysis. In the European Union (EU), venetoclax is approved for use in 
combination with rituximab for patients with CLL who have received at least 1 prior therapy, 
and as a monotherapy in those patients with CLL with del17p or TP53mut who are unsuitable for 
or have not responded to a B-cell receptor pathway inhibitor and those without del17p/TP53mut 
who have not responded to both chemoimmunotherapy and a B-cell receptor pathway inhibitor. 
Approvals for venetoclax monotherapy in the r/r setting were based on 2 single-arm Phase 2 
trials that demonstrated high ORRs of 60% to 80% but low CR/CRi rates of < 10% {Jones 2018, 
Stilgenbauer 2016}. A recent study suggests a high rate of Richter’s transformation 
accompanying progression on venetoclax; in an evaluation of 67 subjects across 3 early phase 
trials, 17 of 25 subjects who progressed manifested Richter’s transformation {Anderson 2017}. 
Even in the era of targeted agents, outcomes for patients with Richter’s transformation remain 
extremely poor with a median OS of 3.3 months in a recent study of 71 subjects following 
treatments targeting B-cell receptor kinases or BCL-2 {Davids 2017}. Furthermore, venetoclax 


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has a significant risk of tumor lysis, particularly for patients with a high disease burden, 
necessitating careful monitoring during intrapatient dose escalation over the course of 5 weeks at 
the time of initiation of therapy; patients at a high risk and some at an intermediate risk for tumor 
lysis may require hospitalization during the initial steps of dose escalation for intensive 
monitoring.
Idelalisib, a first-in-class inhibitor of the p110δ catalytic subunit of the phosphatidylinositol-
4,5-bisphosphate 3-kinase (PI3K) signaling enzyme, is also approved for use in combination 
with rituximab for the treatment of patients with relapsed CLL. The results that led to its 
approval demonstrated a high ORR of 83.6% in subjects previously treated exclusively with 
chemoimmunotherapy but a limited depth of response (0 CRs) {ZYDELIG 2016}. Idelalisib has 
not been studied systematically in CLL following treatment with ibrutinib but the results 
available suggest significantly decreased efficacy, with an estimated ORR to idelalisib of 28% in 
1 retrospective study {Mato 2016}. In a larger multicenter study, a retrospective analysis of 
683 CLL patients treated with kinase inhibitors (KIs) or venetoclax was conducted {Mato 2017}. 
Patients treated with ibrutinib (versus idelalisib) as first KI had a significantly better PFS in all 
settings (frontline, r/r, del17p, complex karyotype). When these patients failed the initial KI and 
were treated with an alternate KI or venetoclax, they had superior PFS compared with 
chemoimmunotherapy. In patients who discontinued ibrutinib due to disease progression or 
toxicity, outcomes were improved if they received venetoclax (ORR of 79%) compared to 
idelalisib (ORR of 46%).
Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment option for 
CLL but is used rarely in the era of targeted therapy, as few patients are good candidates due to 
age and comorbidities. Further, it is accompanied by a significant non-relapse mortality risk from 
acute and chronic graft-versus-host disease (GVHD) in the first 2 years following transplant for 
CLL, approaching 30% in some studies, as well as significant morbidity in at least a quarter of 
patients who do survive {Dreger 2014}. Thus, allogeneic transplant is an unsuitable option for 
most patients.
CAR-modified autologous T cells offer the possibility of yielding high response rates and 
long-term durable responses in CLL without the accompanying morbidity and mortality 
associated with the conditioning treatment or GVHD that accompanies allogeneic transplant. 
CD19 is a 95 kDa transmembrane protein expressed exclusively in the B-cell lineage from 
pro-B cells through mature B cells but not on hematopoietic stem cells or plasma cells 
{Anderson 1984, Gupta 2009, Lin 2004, Nadler 1983, Uckun 1990, Uckun 1988}. CD19 is 
expressed in a number of B-cell malignancies, including non-Hodgkin lymphoma, CLL, and 
B-cell acute lymphocytic leukemia {Anderson 1984, Johnson 2009b, Leonard 2001, Nadler 
1983, Olejniczak 2006, Rodriguez 1994, Uckun 1988}. Anti-CD19 CAR T cells have 
demonstrated high rates of durable responses in patients with r/r acute lymphoblastic lymphoma 
and diffuse large B-cell lymphoma, and clinical trials are currently underway evaluating the 
benefit in other non-Hodgkin lymphomas. Although the treatment experience to date for CLL 
has been more limited, the early experience shows high ORRs (55 to 90%) even in patients 
previously treated with ibrutinib {Kochenderfer 2012, Kochenderfer 2015, Porter 2015, Siddiqi 
2019, Siddiqi 2018, Turtle 2017}. Consistent with a marked depth of response in response to 
anti-CD19 CAR T cells, a subset of patients demonstrate an absence of disease relapse years 
following a single treatment.


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2.2.
KTE-X19
Kite Pharma, Inc. (hereafter referred to as the sponsor), is focused on the development and 
commercialization of engineered autologous cell therapy products that harness the power of a 
patient’s own immune system to selectively target and eradicate cancer cells. Kite is developing 
an anti-CD19 CAR T-cell product for treatment of patients with r/r B-cell malignancies that 
express CD19. CD19 is expressed by most B-cell malignancies {Johnson 2009a, Leonard 2001, 
Olejniczak 2006, Rodriguez 1994, Uckun 1988} as well as all normal B lymphocytes in 
peripheral blood and spleen, but not by granulocytes, monocytes, platelets, erythrocytes, and 
T lymphocytes {Uckun 1988}. Briefly, the anti-CD19 CAR comprises the following domains: an 
extracellular anti-human CD19 single-chain variable region fragment (scFv); the partial 
extracellular domain and complete transmembrane and intracellular signaling domains of human 
CD28, a lymphocyte costimulatory receptor that plays an important role in optimizing T-cell 
survival and function; and the cytoplasmic portion, including the signaling domain, of human 
CD3ζ, a component of the T-cell receptor complex {Nicholson 1997}.  Following CAR 
engagement with CD19+ target cells, the CD3ζ domain activates the downstream signaling 
cascade that leads to T-cell activation, proliferation, and acquisition of effector functions, such as 
cytotoxicity. Additional details regarding the mechanism of action of KTE-X19 can be found in 
the Investigator’s Brochure (IB).  
The manufacture of KTE-X19 begins with collection of the patient’s own T cells via 
leukapheresis. For subjects with high numbers of circulating tumor cells (eg, those with 
B-lineage acute lymphoblastic leukemia, CLL, or mantle cell lymphoma), the T cells in the 
harvested leukocytes undergo a T-cell enrichment step (referred to as the XLP process) that 
removes circulating tumor cells from the leukapheresis material. Additional details regarding the 
manufacture of KTE-X19 are provided in the Investigator’s Brochure.
2.3.
Prior Anti-CD19 CAR T-cell Study Designs and Results
Refer to the current KTE-X19 Investigator’s Brochure (IB) for the most current anti-CD19 
CAR T-cell nonclinical and clinical information. 


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Protocol KTE-C19-108 (ZUMA-8)
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3.
STUDY DESIGN AND RATIONALE
3.1.
General Study Design
KTE-C19-108 (ZUMA-8) is a Phase 1, multicenter, open-label study evaluating the safety and 
tolerability of KTE-X19 in adult subjects with r/r CLL and SLL will be assessed to evaluate the 
safety of KTE-X19. The study will enroll up to approximately 27 subjects with r/r CLL and 
SLLwill be assessed to evaluate the safety of KTE-X19. Two dose levels may be evaluated in the 
study. 
Dose Level
Total anti-CD19 CAR T cells/kg
Starting Dose
1 x 106 
Escalating Dose
2 x 106 
During the study, approximately 15 to 27 subjects with r/r CLL and SLL will be assessed to 
evaluate the safety of KTE-X19. A safety review team (SRT) that is internal to the study 
sponsor, in collaboration with at least 1 study investigator, will review all data available, 
including safety and efficacy data and make recommendations regarding further enrollment 
based on the incidence of DLTs and overall safety profile and cell expansion of KTE-X19. See 
Section 9.7.
The trial will be separated into two different stages:
In the first stage, subjects with r/r CLL will be enrolled using a 6+3 study design into cohorts 
described below:

Cohort 1: Up to 9 subjects will be enrolled at 1 x 106 anti-CD19 chimeric antigen receptor 
(CAR) T cells/kg. Decision to enroll in Cohort 2 will be based on incidence of DLT in 
Cohort 1.

Cohort 2: Up to 9 subjects will be enrolled at 2 x 106 anti-CD19 CAR T cells/kg. 
In the second stage (Amendment 2), subjects with r/r CLL and SLL will be enrolled into 
Cohort 3 and 4 as described below: 

Cohort 3: Three (3) subjects with r/r CLL and SLL with ≤ 1% malignant cells in peripheral 
blood or absolute lymphocyte count (ALC) < 5,000 cells/μL will be enrolled and dosed 
KTE-X19 at a dose of 1 x 106 anti-CD19 CAR T cells/kg. This is an exploratory cohort. No 
additional dose levels will be evaluated.

Cohort 4: Up to approximately 15 subjects with r/r CLL who have been previously treated 
with at least two prior lines of therapy and are receiving ibrutinib as a single agent,  or 
ibrutinib in combination with anti-CD20 antibodies, BCL-2 inhibitors, and PI3k inhibitors as 
the last line of therapy. Subjects must have received ibrutinib for at least 6 months prior to 


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Protocol KTE-C19-108 (ZUMA-8)
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screening. Ibrutinib administration will continue up to 30 hours prior to leukapheresis. In 
case of treatment interruption with ibrutinib, the principal investigator should reach out to the 
medical monitor to discuss. A 3+3 study approach will be used to evaluate two doses of 
KTE-X19.
Cohort 4A: 
■
Up to 6 subjects using 3+3 approach will be enrolled and dosed at 1 x 106 anti-CD19 
chimeric antigen receptor (CAR) T cells/kg. Decision to enroll in Cohort 4B will be 
based on incidence of DLT in Cohort 4A.
■
*Upon completion of Cohort 4A SRT, it was determined not to enroll subjects in 
Cohort 4B.
Cohort 4B: 
■
Up to 6 subjects will be enrolled and dosed at 2 x 106 anti-CD19 chimeric antigen 
receptor (CAR) T cells/kg (escalating dose)
Once a safe dose is established in Cohort 4, additional subjects will be enrolled and dosed for a 
total of up to twelve (12) subjects at the safe dose level (including those who were enrolled 
during the SRT evaluation phase). The maximum number of enrolled and dosed in Cohort 4 will 
be approximately 15 subjects. 
Each subject will proceed through the following study periods:

Screening 

Enrollment/Leukapheresis 
 

Lymphodepleting/conditioning chemotherapy 

Investigational product (IP) treatment 

Post-treatment assessment 

Long-term follow-up. After the end of KTE-C19-108, subjects who received an infusion of 
KTE-X19 will complete the remainder of the 15-year follow-up assessments in a separate 
Long-term Follow-up study (LTFU), KT-US-982-5968.
For study requirements, refer to the schedule of assessments (SOA), Table 3 and Table 4, and 
Section 7 for details.
A study schema is included at the end of the protocol synopsis (Figure 1).
CCI


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
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3.2.
Study Rationale For Cohort 1 and Cohort 2
While chemoimmunotherapy and targeted therapy represent efficacious treatment options for 
CLL, very few patients are cured by currently available treatment short of allogeneic stem cell 
transplant, which is itself limited by treatment-associated morbidity and mortality. Since its 
approval, ibrutinib has become widely used in both previously untreated patients with CLL as 
well as those with r/r disease.   
Second generation BTK inhibitors, such as acalabrutinib, have demonstrated activity in r/r CLL 
patients who have not progressed with prior ibrutinib treatment or in patients who have become 
intolerant to ibrutinib{Awan 2016}. Acalabrutinib has been approved for the treatment of adults 
with CLL as first line therapy as well as in the r/r setting, based on 2 randomized, actively 
controlled trials (ELEVATE-TN and ASCEND trials) {CALQUENCE 2019}. 
Patients who have progressed or are ineligible to receive a BTK inhibitor due to toxicity may 
have limited options that can offer deeper responses. While venetoclax is approved for 
previously treated CLL, it shows limited depth of response in this setting with an accompanying 
significant risk of tumor lysis syndrome and a high rate of progression with Richter’s syndrome. 
Idelalisib has not been studied systematically following ibrutinib treatment though some 
retrospective analyses suggest limited efficacy. Furthermore, chronic treatment with these 
approved targeted agents is necessitated by the absence of deep responses or significant rates of 
MRD−. As treatment with these agents has become more prevalent, the limitations of their 
accompanying toxicity have also become more evident; treatment discontinuations due to AEs 
occur in a significant subset of patients {Maddocks 2015, Mato 2018}.
Engineered autologous cell therapy has the potential to yield long lasting durable responses 
following a single administration. Autologous CAR T cells targeted to CD19 have transformed 
the treatment landscape for r/r diffuse large B-cell lymphoma and acute lymphocytic leukemia 
and are under evaluation for a number of additional B-cell malignancies. Early results with 
anti-CD19 CAR T cells from the National Cancer Institute, University of Pennsylvania, and the 
Fred Hutchinson Cancer Research Center have demonstrated efficacy in CLL with a tolerable 
safety profile.
This study will evaluate the safety and tolerability of KTE-X19 in subjects with r/r CLL and SLL 
who have failed or have become intolerant to a BTK inhibitor.
3.2.1.
Rationale for Cohort 3 
In this cohort, the sponsor will explore if enrollment of subjects with a diagnosis of r/r SLL or 
r/r CLL who present with ≤ 1% circulating tumor cells (low tumor burden) in peripheral blood 
demonstrate meaningful CAR T-cell expansion. One subject enrolled in ZUMA-8 Cohort 1 who 
presented with a low circulating tumor burden achieved meaningful expansion of CAR T cells 
and a PR (Data on File). The published experience from the NCI of 8 subjects with r/r CLL 
treated with anti-CD19 CAR-transduced T cells (using the same construct used in this study) 
demonstrated a robust expansion of CAR T cells in subjects who had low circulating CLL 
burden with a median pre-apheresis ALC of 0.54 x 103 cells/uL.


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Protocol KTE-C19-108 (ZUMA-8)
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A phase 1 study conducted at Memorial Sloan Kettering Cancer Center, investigated 
CD-19-targeted CAR T-cells incorporating a CD28 costimulatory domain {Geyer 2019}. The 
study included 16 patients with r/r CLL. The analysis of disease burden (absolute lymphocyte 
counts) of these patients at the time of CAR T-cell infusion, showed a median value of 2.35 x 103 
cells/uL, which is lower compared with the median value of 7.2 x 103 cells/uL found in 
10 subjects dosed with KTE-X19 in ZUMA-8 study, cohorts 1 and 2.
3.2.2.
Rationale for Cohort 4 {Geyer 2019}
3.2.2.1.
Introduction
Only 10 to 30% of CLL patients treated with chemoimmunotherapy or targeted therapies achieve 
CR or MRD−, and 50% of these patients relapse within 3 to 4 years {Bottcher 2012, Strati 2014}. 
Patients who progress on targeted agents have limited options and shortened OS {Anderson 
2017, Mato 2016}. 
Initial clinical trials with CAR T cells in r/r CLL aimed to address the feasibility and proof of 
concept of monotherapy with CAR T cells targeting the pan-B-cell marker CD19. Early clinical 
results showed ORR of 71% in this heavily pretreated patient population {Turtle 2017}. The 
immune dysregulation observed in patients with CLL is well characterized, and intrinsic T-cell 
defects impose a significant barrier to both the feasibility of generating CAR T cells and the 
responsiveness of the disease to CAR T-cell-based therapy. One of the most critical determining 
factors for the success of CAR T cells is the expansion and persistence of antigen-specific T cells 
{Robbins 2004}. Additionally, the response of CLL to CAR T-cell therapy is influenced by the 
composition of the cellular product and/or T-cell fitness {Fraietta 2018}. 
The following preclinical and clinical data are intended to support the rationale of including 
Cohort 4 in this study, in which subjects must have been exposed to ibrutinib for at least 6 
months prior to screening, to test if this exposure prior to leukapheresis has a positive impact on 
T-cell fitness, with the goal of increasing expansion of CAR T cells through ibrutinib’s 
modulatory effect on T-cell function. 
3.2.2.2.
Preclinical Data
Ibrutinib exerts its immunomodulatory effects by inhibiting BTK and IL-2 inducible T cell 
kinase (ITK) signaling. Peripheral blood mononuclear cells (PBMC) from 19 subjects with CLL 
treated with ibrutinib were evaluated for T-cell phenotype, immune function, and CLL cell 
immunosuppressive capacity. Results showed that ibrutinib treatment increased in vivo 
persistence of activated T cells, decreased the Treg/CD4+ T-cell ratio, and diminished the 
immune-suppressive properties of CLL cells through BTK-dependent and independent 
mechanisms {Long 2017}. It was demonstrated that the influence of ibrutinib in subjects with 
CLL also has a direct positive influence on the immunosuppressive capacity of the primary 
tumor cells, reducing the expression of the immunosuppressive molecules CD200 and BTLA as 
well as IL-10 production by CLL cells {Long 2017}. 


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Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
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In addition, ibrutinib, through ITK inhibition, enables pleotropic effects on the various T-cell 
subsets including enhancing expansion of activated T cells, while having no deleterious effects 
on the central memory T cells (Tcm) or naïve T cells; no collateral expansion of the regulatory 
T cells (Treg cells); and partially reversing the exhausted T-cell phenotype by reducing the 
expression of PD-1 and CTLA4 {Long 2017}. Preclinical evidence demonstrated that ibrutinib, 
when administered concurrently with CAR T cells, improves CAR T-cell engraftment, tumor 
clearance, and survival in human xenograft models of acute lymphocytic leukemia and CLL 
{Fraietta 2016}. Specifically, treatment with ibrutinib for ≥ 5 cycles (28 days of treatment was 
considered 1 cycle) had a positive impact on the impaired T-cell function in patients with CLL 
through its modulation of T-cell function. In summary, ibrutinib improved expansion of 
CD19-directed CAR T cells (CTL019) in association with decreased expression of PD-1 on 
T cells {Fraietta 2016}.
3.2.2.3.
Clinical Data
Evidence showed that T cells collected from subjects exposed to ibrutinib had greater ex vivo 
expansion and a greater fraction of T cells with a Tcm phenotype compared to T cells from 
subjects with CLL who were not receiving ibrutinib. The ORR for subjects who had received 
concurrent ibrutinib was 80%, whereas the ORR for all subjects was only 38% {Geyer 2019}.
In a prospective trial combining a humanized CD19-targeted CAR T cell (CTL119) with 
ibrutinib, the ORR at 3 months in 14 evaluable subjects was 71% with 6 CRs (43%) {Gill 2018}. 
At 3 months, 17 of 18 subjects (94%) demonstrated a morphologic CR within the marrow and 
15 of 17 subjects were MRD− by high resolution flow cytometry. Fourteen of 18 subjects were 
MRD− by IgH sequencing.
In a Phase 1/2 study, it was observed that subjects who received concurrent treatment with 
ibrutinib (420 mg/day) from at least 2 weeks before leukapheresis until at least 3 months after 
JCAR014 CAR T-cell infusion had a higher proportion of responders (CR and PR) by 
International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria in the ibrutinib 
cohort (14 of 16 evaluable subjects, 88%) compared to the non-ibrutinib cohort (10 of 
18 evaluable subjects, 56%) {Gauthier 2018}. 
In a Phase 1 clinical trial investigating CD19-targeted CAR T cells incorporating a CD28 
costimulatory domain (19-28z), ex vivo expansion of T cells and proportions of CD4+/CD8+ 
CAR T cells with a CD62L+ CD127+ immunophenotype were significantly greater in subjects 
who were receiving ongoing therapy with  ibrutinib at leukapheresis {Geyer 2019}. Three of 
12 evaluable subjects with CLL receiving conditioning chemotherapy with 
cyclophosphamide/bendamustine or fludarabine/cyclophosphamide achieved CR (2 had 
MRD− CR). All subjects achieving CR remained progression-free with a median follow-up of 
53 months. 
A recent pilot study  reported the treatment of 19 subjects with CLL with anti-CD19 
CAR T-(4-1BB and CD3z signaling domains) These patients were treated after ibrutinib failure. 
{Gauthier 2020}. Patients were heavily pretreated ( median number of prior therapies was 5), 
and 17 subjects (89%) had high-risk cytogenetics (del17p and/or complex karyotype). The 
minimal time to exposure to ibrutinib was  2 weeks prior to leukapheresis and ibrutinib was 


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
continued for at least 3 months after CAR T-cell infusion. Thiiteen subjects ( 68%) received 
ibrntinib as planned in the protocol without dose reduction. The ORR by IWCLL criteria 
assessed at 4 weeks after the infusion was 83%, and 61 % achieved MRD-. The I-year OS and 
PFS probabilities were 86% and 59%, respectively. Compared to subjects with CLL who were 
treated with CAR T cells without ibrntinib, Subjects ti·eated with CAR T cells with concunent 
ibrntinib, compared to subjects ti·eated with CAR T cells without ibrntinib, showed was lower 
severity of cytokine release syndrome (CRS) and lower sernm concenti·ations of CRS-associated 
cytokines despite equivalent in vivo CAR T-cell expansion. 
Other non-randomized studies to prospectively evaluate the combination of ibrntinib and CAR T 
cells are cunently ongoing (NCT03331198, NCT02640209). 
In summa1y, in order to improve the acquired T-cell dysfunction in r/r CLL, prior exposure to 
ibrntinib, before leukapheresis may lead to improved T-cell fitness and thereby enhance the 
ability of CAR T cells to expand in vivo and exe1t anti tumor effects. 
3.2.3. 
Rationale for Conditioning Chemotherapy 
Increasing levels of conditioning chemotherapy con elates with clinical responses to adoptive cell 
therapy {Dudley 2008}. Specifically, there appears to be a link between adequate 
lymphodepletion and adoptively u-ansfened T-cell expansion and function in preclinical models, 
which demonsti·ate that the depth and duration of lymphodepletion conelates with anti-tumor 
activity of the adoptively u-ansfened tumor-specific CD8+ T cells { Gattinoni 2005}. 
Lymphodepletion may function by eradicating cytokine sinks for the transfened cells, 
eliminating T regulato1y cells, or enhancing antigen-presenting cell activation {Klebanoff 2005}. 
Cyclophosphamide and fludarabine combination is a potent lymphodepleting regimen. 
Cyclophosphamide (500 mg/m2/day) and fludarabine (30 mg/m2/day) are both given for 
3 consecutive days. This combination has been studied in subjects with B-cell malignancies and 
was tolerated by this population {O'Brien 2001} and was also used in the ZUMA-I ti·ial 
{Neelapu 2017}. 
3.2.4. 
Rationale for KTE-X19 Dose 
The initial dose level of 1 x 106 anti-CD19 CART cells/kg has been previously shown to be safe 
and tolerable for subjects with r/r acute lymphocytic leukeinia (KTE-C19-103/ZUMA-3) and 
mantle cell lymphoma (KTE-C19-102/ZUMA-2). The 2 dose levels of KTE--X19 proposed for 
this study have been previously evaluated in the KTE-C19-103 study, with only 1 DLT at the 
2 x 106 anti-CD19 CART cells/kg dose level; this dose level has also been deemed to be safe and 
tolerable for sub'ects with mantle cell l 
homa in KTE-C19-102. KTE-X19 is 
approved by the FDA at a dose of2 x 10 anti-CD19 
or t e ti·eatment of patients with r/r large B cell lymphoma. 
3.3. 
Overall Risk and Benefit Assessment 
Kite is developing KTE-X19, an anti-CD19 CAR T-cell product for ti·eatment of patients with r/r 
B-cell malignancies that express CD 19. 
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Protocol KTE-C19-108 (ZUMA-8)
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While chemoimmunotherapy and targeted therapy represent efficacious treatment options for 
CLL, the limited depth of response from currently approved targeted agents for CLL underlies 
the ongoing inability to yield durable responses with finite therapy or to result in a cure for 
patients with CLL. Also, while allogeneic hematopoietic stem cell transplantation is a potentially 
curative treatment option for CLL, it is now rarely used as few patients are appropriate 
candidates due to age and comorbidities.
CAR T-cell therapy offers the possibility of yielding deep MRD− responses and long-term 
durable responses in CLL without the morbidity and mortality associated with the conditioning 
treatment or the GVHD of allogeneic transplant. Although the treatment experience to date for 
CLL has been limited, the early experience shows high rates of response (55 to 90%), with up to 
88% MRD−, even in subjects previously treated with ibrutinib {Kochenderfer 2012, 
Kochenderfer 2015, Porter 2015, Siddiqi 2019, Siddiqi 2018, Turtle 2017}. A subset of subjects 
remain relapse-free years following a single treatment, evincing a marked depth of response due 
to anti-CD19 CAR T cells.
KTE-X19 is administered as a single dose following conditioning chemotherapy, and the 
majority of AEs occur within 30 days of infusion. AEs, which can be severe or even fatal, are 
well defined, generally reversible, and manageable with no apparent long-term consequences 
other than B-cell aplasia. The most common events were cytopenias, which are expected from 
the conditioning chemotherapy, as well as infections, CRS, and neurologic events. Guidelines for 
management of these AEs are described in the Investigator’s Brochure (IB), Section 6.5.
The IB also contains the current understanding of the pathophysiology of CRS/neurotoxicity, and 
clinical trials experience across KTE-X19 studies to provide context and rationale for 
management. Furthermore, all sites are trained by the Kite medical monitor on toxicity 
management including CRS and neurological toxicity at the site initiation visit, and new sites are 
retrained at first dosing of KTE-X19. Kite provides regular Investigator calls and meetings as 
well as a toxicity management tool so that sites have quick access to relevant information.
In summary, the rates and durations of high quality clinical responses anticipated within the 
KTE-X19 study design, the demonstrated safety profile of KTE-X19 to date in other malignant 
B-cell diseases, and the planned safety monitoring plan (SRT) in this study suggest that the 
benefits of study participation will outweigh the risks for these subjects with r/r CLL and SLL.
3.4.
Participating Sites
Approximately 22 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.
3.5.
Number of Subjects
Participants in this trial will be referred to as “subjects.” It is anticipated that up to approximately 
27 subjects will be enrolled and dosed in this study.


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Protocol KTE-C19-108 (ZUMA-8)
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3.6.
Replacement of Subjects
Subjects may continue to be enrolled until the specified approximate number of subjects are 
dosed with KTE-X19 in Phase 1 for safety evaluation (see Section 10.6). 
3.7.
Study Duration
3.7.1.
Study Duration for Individual Subjects 
The duration of the study 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 3.7.3). 
3.7.2.
Completion of Study
Completion of the study is defined as the time at which the last subject completes at least 
3 months of assessments (the post-treatment follow-up period), is considered lost to follow-up, 
withdraws consent, or dies. Upon activation of KT-US-982-5968 at subject study site, the subject 
will be offered the opportunity to complete long-term follow-up assessments under the KT-US-
982-5968 protocol. 
3.7.3.
Long-term Follow-up 
All subjects who received an infusion of KTE-X19 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/SAEs suspected to be possibly related to KTE-X19, presence of 
replication-competent retrovirus (RCR), and/or insertional mutagenesis for up to 15 years from 
the time of KTE-X19 infusion (also refer to Section 7.13).
In KT-US-982-5968, subjects will continue assessments at timepoints contiguous with the LTFU 
timepoints in this study. 


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Protocol KTE-C19-108 (ZUMA-8)
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4.
SUBJECT IDENTIFICATION ASSIGNMENT
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 number will never be changed even if the subject is 
rescreened.


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Protocol KTE-C19-108 (ZUMA-8)
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5.
SUBJECT ELIGIBILITY
5.1.
Inclusion Criteria
Subjects must meet all of the following criteria to be eligible for enrollment:
101. Documentation of relapsed or refractory CLL and SLL; subjects must have received at 
least 2 prior lines of treatment, one of which must include a BTK inhibitor 
a.
Cohort 1 and 2: Subjects with r/r CLL who have received at least 2 prior lines of 
treatment, one of which must include a BTK inhibitor
b. Cohort 3: Subjects with r/r CLL and SLL must present with ≤ 1% circulating tumor 
cells in peripheral blood or ALC < 5000 cells/μL. Subjects must have received at least 
2 prior lines of treatment, one of which must include a BTK inhibitor.
c.
Cohort 4: Subjects with r/r CLL who have received at least 2 prior lines of treatment 
and must have received ibrutinib as a single agent or in combination with anti-CD20 
antibodies, BCL-2 inhibitors, and PI3k inhibitors for at least 6 months as the last line of 
therapy prior to screening. Ibrutinib administration will continue up to 30 hours prior to 
leukapheresis. In case of treatment interruption with ibrutinib, the principal investigator 
should reach out to the medical monitor to discuss. 
102. An indication for treatment per IWCLL 2018 criteria {Hallek 2018} and radiographically 
measurable disease (at least 1 lesion > 1.5 cm in diameter)
103. Adequate hematologic function as indicated by:
a.
Platelet count ≥ 50 × 109/L
b. Neutrophil count ≥ 0.5 × 109/L
c.
Hemoglobin ≥ 8 g/dL 
Unless lower values are attributable to CLL
104. Adequate renal, hepatic, cardiac and pulmonary function defined as:
a.
Creatinine clearance (as estimated by Cockroft-Gault) ≥ 60 mL/min
b. Serum ALT/AST ≤ 2.5 x upper limit of normal (ULN)
c.
Total bilirubin ≤ 1.5 mg/dL unless subject has Gilbert’s syndrome
d. Left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial effusion, 
no NYHA class III or IV functional classification, no clinically significant arrhythmias


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Protocol KTE-C19-108 (ZUMA-8)
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e.
No clinically significant pleural effusion
f.
Baseline oxygen saturation > 92% on room air
105. Age 18 or older
106. ECOG performance status of 0 or 1
107. 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)
108. 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)
5.2.
Exclusion Criteria
Subjects meeting any of the following exclusion criteria are not eligible for enrollment:
201. A history of treatment including any of the following:
a.
Prior CD19 directed therapy
b. Treatment with alemtuzumab within 6 months before enrollment
c.
Allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte infusion 
(DLI) within 6 months prior to enrollment
d. Live vaccine administration within 4 weeks before enrollment
e.
Systemic immunosuppression or systemic treatment for any autoimmune disease not 
related to CLL in the 2 years before enrollment
202. Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index
203. History of autoimmune disease resulting in end-organ injury unless attributable to CLL 
(eg, ITP, AIHA)
204. Diagnosis of Richter’s transformation or a history of malignancy.  Exceptions include: 
a.
Non-melanoma skin cancer or carcinoma in situ (eg, skin, cervix, bladder, breast) 
b. Superficial bladder cancer 


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c.
Asymptomatic localized low grade prostate cancer for which watch-and-wait approach 
is standard of care 
d. Any other cancer that has been in remission for > 3 years prior to enrollment
205. History of severe hypersensitivity reaction attributed to aminoglycosides or any of the 
agents required for treatment in this study
206. CNS disease including:
a.
Known presence of involvement by CLL/SLL
b. History of any CNS disorder such as seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS 
involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema 
with confirmed structural defects (eg, by whole-neuroaxis magnetic resonance imaging 
[MRI])
Note: Subjects with a history of seizures requiring antiseizure therapy are excluded. 
207. History of concomitant genetic syndrome associated with bone marrow failure such as 
Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome
208. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other 
clinically significant cardiac disease within 12 months before enrollment
209. History of symptomatic deep vein thrombosis or pulmonary embolism requiring systemic 
anticoagulation within 6 months before enrollment. Subjects taking prophylactic 
anticoagulation are eligible. 
210. Primary immunodeficiency
211. History of human immunodeficiency virus (HIV) infection or acute or chronic active 
hepatitis B or C infection.  Subjects with history of hepatitis infection must have cleared 
their infection as determined by standard serological and genetic testing per current 
Infectious Disease Society of America (IDSA) guidelines or applicable country guidelines. 
212. Presence of active fungal, bacterial, viral infection or any infection requiring antimicrobial 
treatment for management. Simple UTI and uncomplicated bacterial pharyngitis are 
permitted if responding to active treatment and after consultation with the Kite medical 
monitor
213. Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling 
Foley catheter, biliary drain, pleural/peritoneal/pericardial catheter). Ommaya reservoirs 
and dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are 
permitted


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214. Women of childbearing potential who are pregnant or breastfeeding because of the 
potentially dangerous effects of the preparative chemotherapy on the fetus or infant.  
Females who have undergone surgical sterilization or who have been postmenopausal for 
at least 2 years are not considered to be of childbearing potential.
215. Subjects of childbearing potential who are not willing to practice birth control from the 
time of consent through 6 months after the administration of conditioning chemotherapy or 
KTE-X19, whichever is longer. 
216. In the investigator’s judgment, subject is unlikely to complete all protocol-required study 
visits or procedures including follow-up visits or comply with requirements for participation
217. Any medical condition likely to interfere with assessment of safety or efficacy of study 
treatment


KTE-X19 
Protocol KTE-Cl9-108 (ZUMA-8) 
6_ 
6.1. 
6.1.1. 
PROTOCOL TREATMENT 
Study Treatment 
Leukapheresis 
Kite Pha1ma, Inc. 
Amendment3 
Leukapheresis refers to the procedure for collecting PBMCs that are used to manufacture the 
subject-specific KTE-X19. 
Subjects will undergo leukapheresis to obtain T cells for the manufacturing of KTE-X19. 
Leukapheresed cells obtained at paiticipating centers will be shipped to the sponsor's 
manufacturing facility as described in the Investigational Product Manual (1PM). 
-
I 
I 
6.1.3. 
Conditioning Chemotherapy 
Conditioning chemotherapy refers to fludarabine and cyclophosphamide used for 
lymphodepletion prior to administration of KTE-X19. 
Conditioning chemotherapy will be supplied by the investigative site unless othe1w ise noted. 
Refer to the cmTent product label for guidance on packaging, storage, prepai·ation, 
administration, and toxicity management associated with the administration of chemotherapy 
agents. 
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The investigational medicinal product (KTE-X19) must be available before initiation of 
conditioning chemotherapy.
6.1.3.1.
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.
6.1.3.2.
Cyclophosphamide
Cyclophosphamide is a nitrogen mustard-derivative that acts as an alkylating agent following 
conversion to active metabolites in the liver and has potent immunosuppressive activity. The 
serum half-life after intravenous (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.
6.1.3.3.
Mesna
Mesna is a detoxifying agent used to inhibit the hemorrhagic cystitis induced by chemotherapy. 
The active ingredient in mesna is a synthetic sulfhydryl compound designated as sodium-2-
mercaptoethane sulfonate with a molecular formula of C2H5NaO3S2. 
Mesna should be administered per institutional guidelines.  Refer to the most recent version of 
the package insert for specific details surrounding the administration of mesna.
6.1.4.
KTE-X19 
KTE-X19 is the IP for this study. 
KTE-X19 is supplied cryopreserved in cryostorage bags.  The product in the bag is slightly 
cloudy and cream to yellow color.  The cryostorage bag containing KTE-X19 arrives frozen in a 
liquid nitrogen dry shipper.  The bag must be stored in vapor phase of liquid nitrogen and remain 
frozen until the subject is ready for treatment to assure that 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.  The product is labelled per local regulations with the 
subject’s unique subject ID number assigned at the time of screening.  Upon receipt, verification 
that the product and subject-specific labels match the subject’s information (eg, 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. 


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The product must not be thawed until the subject is ready for the infusion. Refer to the IPM for 
details and instruction on storage, thawing, and administration of KTE-X19. 
There have been no instances of accidental overdose of subjects in this program to date.  In case 
of accidental overdose, treatment should be supportive. Corticosteroid therapy may be 
considered if any dose is associated with severe toxicity.
If any problems related to the use of KTE-X19 or any products that support the management of 
KTE-X19 (eg, cryostorage bags, subject ID labels) are identified, research staff should report the 
problem per the instructions in the IPM. 
6.2.
Concomitant Therapy
Concomitant therapy refers to treatment that subjects receive during the conduct of the study.
Investigators may prescribe any concomitant therapies deemed necessary to provide adequate 
supportive care except those medications listed in Section 6.3.
The investigator is responsible for reporting all concomitant medications as follows:
Table 1.
Reporting Requirements for Concomitant Medications
Subjects who screen-fail
Subjects who are enrolled, but do 
not receive KTE-X19 infusion
Subjects who are enrolled and receive 
KTE-X19 infusion
Concomitant therapies 
related to serious adverse 
event(s) will be recorded.
Concomitant therapies will be 
recorded from the date of the 
informed consent until 30 days after 
the last study-specific procedure has 
occurred (eg, leukapheresis, 
conditioning chemotherapy) or until 
the initiation of new anticancer 
therapy, whichever occurs first.

Concomitant therapies including 
medications, intubation, dialysis, 
oxygen, and blood products will be 
recorded from the date of the informed 
consent until 3 months after 
completing treatment with KTE-X19.  

After this 3-month follow-up period, 
targeted concomitant therapies will be 
recorded for either 24 months after 
KTE-X19 infusion or until disease 
progression, whichever occurs first.  
o
Targeted concomitant therapies 
include gammaglobulin, 
immunosuppressive drugs, anti-
infective drugs, and vaccinations.  
Specific concomitant therapy collection requirements and instructions are included in the case 
report form (CRF) completion guidelines.
6.3.
Excluded Medications
Excluded medications refer to treatment that is not to be administered, unless otherwise 
specified, during the conduct of the study.


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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 KTE-X19 administration. 
Systemic corticosteroids may not be administered as premedication to subjects for whom CT 
scans with contrast are contraindicated (ie, subjects with contrast allergy or impaired renal 
clearance).  Such subjects should undergo non-contrast CT scans instead. 
Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months after 
KTE-X19 administration unless used to manage severe KTE-X19-related toxicities. Other 
medications that might interfere with the evaluation of KTE-X19, such as nonsteroidal 
anti-inflammatory agents, should also be avoided for the same period unless medically 
necessary. 
Therapeutic doses of systemic anticoagulants, such as unfractionated heparin and low-molecular 
weight heparin, should be avoided anytime subjects are at risk of bleeding due to 
thrombocytopenia when possible.
Non-study treatment for CLL/SLL is prohibited prior to disease progression on study. 
If permissibility of a specific medication/treatment is in question, contact the Kite medical 
monitor. 
6.4.
Subsequent Therapy
Subsequent therapy refers to treatment administered after KTE-X19 that is necessary to treat a 
CLL/SLL.
Subsequent therapy such as non-study specified chemotherapy, immunotherapy, targeted agents, 
SCT, or radiation therapy, will be recorded for all enrolled 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 KTE-X19 infusion, any additional anticancer 
therapy will also be collected until the subject completes the participation in the current study, is 
considered lost to follow up, withdraws consent, or dies. 


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7.
STUDY PROCEDURES
Research staff should refer to the SOA Table 3 and Table 4 for an outline of the procedures 
required. Additional information related to a few study assessments/procedures is further 
described below. 
The visit schedule is calculated from KTE-X19 infusion on Day 0. 
Refer to the CRF completion guidelines for data collection requirements and best practices for 
documentation of study procedures.
7.1.
Informed Consent
Before a subject participates in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequately explaining the study design, 
anticipated benefits, and potential risks.  Subjects should sign the most current Institutional 
Review Board/Independent Ethics Committee (IRB/IEC) approved informed consent form (ICF) 
before any study-specific activity or procedure is performed.
The consent process and the subject’s agreement or refusal to participate in the study must be 
documented in the subject’s medical records.  If the subject agrees to participate, the ICF must be 
signed and dated by both the subject and the person who conducted the informed consent 
discussion.  The original signed ICF will be retained in accordance with institution policy and 
IRB/IEC requirements, and a copy of the ICF will be 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 the new version is relevant to their participation.
7.2.
Screening
Investigative sites will maintain a log of all screened subjects who were reviewed and evaluated 
for study participation.  Information collected in 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.
The screening period begins on the date the subject signs the IRB/IEC-approved ICF and 
continues through confirmation of eligibility into the study.  Informed consent must be obtained 
before completion of any non-SOC study-specific procedures.  Procedures that are part of SOC 
are not considered study-specific and, therefore, may be performed prior to obtaining consent 
and used to confirm eligibility provided they occur within the time allowance outlined below and 
in the SOA.
After written informed consent has been obtained, Kite Pharma, Inc., will assign a screening 
number to the subject, as described in Section 7.1. 
See Section 7.2.1 for the study procedures for subjects who rescreen into the study.  


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Only subjects who meet the eligibility criteria listed in Section 5 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.
Refer to the SOA for a listing of study procedures to be completed during the screening period. 
7.2.1.
Rescreening
Subjects who do not 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 assigned at the 
original screening.  If rescreening occurs within 28 days of the signing of the original informed 
consent, it is only necessary to perform the procedure(s)/assessment(s) that did not originally 
meet the eligibility criteria; 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 informed consent, subjects must be re-consented and repeat all screening 
procedures/assessments.
7.3.
Demographic Data
Demographic data will be collected as per country and local regulations and guidelines. Where 
applicable, demographic data will include sex, year of birth, race, ethnicity, and country of 
enrollment to study a possible association between these variables and subject safety and 
treatment effectiveness.
7.4.
Medical and Treatment History
Relevant medical history prior to the start of AE reporting (see Section 9.2) will be collected. 
Relevant medical history is defined as data on the subject’s current medical condition that would 
be typically shared in a referral letter.  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. All findings will be recorded in the CRFs.
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.
7.5.
Physical Exam, Vital Signs, and Performance Status 
Physical exams will be performed during screening and at times noted in the SOA. All physical 
exam changes noted in subsequent exams when compared to the baseline exam will be reported 
as AEs per Section 9.1. Subjects with new-onset symptoms related to CRS should undergo 
physical exam at least daily until symptoms resolve to baseline.  
Vital signs, including blood pressure, heart rate, respiratory rate, oxygen saturation, and 
temperature, will be monitored and recorded at screening and at times outlined in the SOA. In 
addition to the time points outlined in the SOA, it is recommended that vital signs are monitored 
during and after the KTE-X19 infusion and as clinically indicated. 


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Performance status as measured by the ECOG scale will be performed to quantify the subject’s 
general well-being and ability to perform activities of daily life.
7.6.
Cardiac Function
Each subject’s cardiac function, as measured by LVEF, will be assessed during the screening 
period to confirm study eligibility.  No evidence of pericardial effusion will also be confirmed, 
per study eligibility criteria.  LVEF may be assessed by echocardiogram (ECHO) or MUGA, and 
pericardial effusion may be assessed by ECHO or CT/MRI.  Imaging that was performed after 
the subject’s last chemotherapy treatment may also be used to confirm eligibility, provided that it 
occurred ≤ 28 days prior to signing the consent.
To establish a baseline, a 12-lead electrocardiogram (ECG) will also be performed during the 
screening period.
7.7.
Neurological Examination
Subjects neurological status should be evaluated at screening to establish a baseline. After 
enrollment, subjects should be evaluated for any neurological symptoms at each of the 
timepoints specified in the SOA. During the hospitalization period, evaluations of neurological 
status may need to be increased.  Changes in neurological status (level of consciousness, 
orientation, vision, cranial nerves and brain stem functions, pyramidal and extra pyramidal motor 
system, reflexes, muscle tone and trophic findings, coordination, sensory system, and 
neuropsychological findings (eg, speech, cognition and emotion)) should be reported as an AE 
per Section 9.
For new onset of neurologic symptoms (eg, severe headaches, neck stiffness, seizures, 
encephalopathy, cranial nerve deficits, or any focal neurologic findings on physical exam), 
neurologic assessment should be performed at least daily until symptoms resolve to baseline. In 
addition, brain imaging should be considered. 
Subjects with new onset Grade ≥ 2 neurologic symptoms post-KTE-X19 infusion will have a 
lumbar puncture (LP) performed to evaluate for potential causes. A portion of the cerebrospinal 
fluid (CSF) will be submitted to the central lab for evaluation of KTE-X19 levels and cytokines.
7.8.
Disease Assessment 
Binet and Rai staging will be assessed at screening (Appendix 1). Subjects will be evaluated for 
disease response by the site investigator at times indicated in the SOA.  Disease response 
assessments will be per IWCLL 2018 criteria {Hallek 2018}, (Appendix 3). Laboratory samples 
to assess disease response will be collected and evaluated per the SOA and are outlined in 
Section 7.14. 
7.8.1.
Radiology Assessment
Diagnostic quality contrast-enhanced (unless contraindicated) CT (preferred) or MRI of the head, 
neck, chest, abdomen and pelvis must be performed within 28 days before enrollment to confirm 
eligibility. Scans obtained as part of SOC before signing of the ICF and within 56 days before 
enrollment can be used for eligibility. 


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If the subject received treatment for CLL/ SLL after the eligibility images were obtained, then 
additional baseline images must be taken after the com letion of CLL/SLL treatment and within 
28 da s before conditionin chemothera . 
The same imaging modality should be used when possible for post-treatment response 
assessments as outlined in the SOA and in the event of suspected disease progression. See 
Section 7.7 for imaging requirements for nemological symptoms. 
7.8.2. 
Bone Marrow Assessment 
A bone manow aspirate and biopsy is required per the SOA at the following timepoints: 
• 
Screening or prior to conditioning chemotherapy (if applicable) 
• 
Day 28 
• 
Month6 
-
The Month 6 bone manow evaluation is not required if the subject is confmned to be 
MRD- per bone manow evaluation prior to Month 6. 
• 
Subsequent to any evaluation following Day 28 when the subject's hematologic and 
radiographic response becomes consistent with CR/CRi with peripheral blood MRD- in order 
to establish a CR/CRi with bone manow MRD- per IWCLL 2008 criteria (see Appendix 3). 
In addition, a bone manow evaluation (biopsy and/or aspirate) should be perfo1med at the 
following timepoints: 
• 
For persistent cytopenias and to diagnose hemophagocytic lymphohistiocytosis (HLH) if 
appropriate. Refer to the IB for additional infonnation. 
• 
At the time of progressive disease. 
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I 
Whenever obtained, a po1iion of the bone man ow aspirate and biopsy specimen must be sent to 
the central laborato1y for analysis. 
7.9. 
7.9.1. 
7.9.1.1. 
Cell Collection and Study Treatment Schedule and Administration 
Leukapheresis 
Requirements for Initiating Leukapheresis 
Before leukapheresis commences, the following criteria must be met: 
• 
Subjects must remain eligible per the eligibility criteria outlined in Section 5 prior to the start 
of leukapheresis. 
• If any screening assessments or procedures are repeated between confinnation of eligibility 
and the staii of leukapheresis and results ai·e outside the eligibility criteria listed in Section 5, 
contact Kite's medical monitor prior to proceeding with leukapheresis. 
• 
No evidence or suspicion of an infection 
• 
Co1iicosteroid therapy at a phaimacologic dose (~ 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive diugs must be avoided for 
7 days prior to leukapheresis 
• If criteria are not met, leukapheresis must be delayed until the event resolves. If 
leukapheresis is delayed more than 5 days after eligibility confmnation, baseline complete 
blood count (CBC) with differential and chemistry panel must be repeated. If results are 
outside the eligibility criteria listed in Section 5, contact the medical monitor prior to 
proceeding with leukapheresis. 
The leukapheresis visit should occur within approximately 5 days of eligibility confnmation. 
After a subject commences leukapheresis, the subject will be considered emolled into the study. 
After the above criteria ai·e met, mononucleai· cells will be obtained by leukapheresis 
(12 to 15 L) apheresis with a goal to tai·get approximately 5 to 10 x 109 mononucleai· cells. The 
leukapheresed cells ai·e then packaged for expedited shipment to the manufacturing facility as 
described in the IPM. 
Refer to the SOA Table 3 for a listing of study procedures to be completed on the leukapheresis 
collection day. 
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7.9.3.
Conditioning Chemotherapy and KTE-X19 Infusion
Administration of 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 C-reactive protein 
[CRP]) are diagnoses of exclusion that require a documented workup to establish.  Conditioning 
chemotherapy and KTE-X19 infusion should be initiated only once it is reasonably assured that 
cell infusion can safely proceed.
Refer to Section 7.9.4 for Requirements to Work-up Potential Infectious and/or Inflammatory 
States.
7.9.3.1.
Conditioning Chemotherapy Period
7.9.3.1.1.
Requirements for Initiating Conditioning Chemotherapy
If any of the following criteria are met prior to the initiation of conditioning chemotherapy, then 
the work-up listed in Section 7.9.4 must be performed to determine the potential cause if there is 
no identified source of infection.  

Temperature > 38 degrees Celsius within 72 hours of conditioning chemotherapy

CRP > 100 mg/L anytime between enrollment to start of conditioning chemotherapy

White blood cell (WBC) count or WBC differential concerning for infectious process 
between enrollment to start of conditioning chemotherapy (eg, WBC > 20,000, 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, then the condition must resolve prior to proceeding with conditioning 
chemotherapy.

Complete history and physical exam including head, ears, eyes, nose, and throat (HEENT), 
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 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.
Once the above criteria are met, then the subject can proceed with conditioning chemotherapy.
7.9.3.1.2.
Conditioning Chemotherapy Administration (Day –5 Through Day –3 Prior to 
KTE-X19 Infusion)
Subjects will receive a conditioning chemotherapy regimen consisting of cyclophosphamide and 
fludarabine.  The first dose of conditioning chemotherapy will be designated as Day –5. Subjects 
will initiate conditioning chemotherapy with cyclophosphamide and fludarabine beginning on 
Day –5 and through Day –3, with 2 rest days (Day –2 and Day –1) before receiving KTE-X19. 
The 3-day conditioning chemotherapy regimen will be administered in an outpatient setting. 
Before conditioning chemotherapy commences, the criteria outlined in Section 7.9.3.1.1 must be 
met.
Provided the criteria for conditioning chemotherapy are met, the 3-day conditioning regimen of 
fludarabine and cyclophosphamide will be administered in accordance with the following daily 
dosing instructions.

IV hydration with a balanced crystalloid according to institutional guidelines prior to 
administration of cyclophosphamide on the day of infusion

Cyclophosphamide 500mg/m2/day IV over approximately 30-60 minutes

Fludarabine 30mg/m2/day IV over approximately 30 minutes 

Additional IV hydration with a balanced crystalloid according to institutional guidelines to be 
administered upon completion of the cyclophosphamide infusion

Mesna to be administered per institutional guidelines
Subjects should be instructed to drink plenty of liquids during chemotherapy and throughout the 
24-hour period following chemotherapy (approximately 2 L/24 hours). In general, subjects 
should be kept well-hydrated but closely monitored to prevent fluid overload. 
Refer to the SOA Table 3 for a listing of study procedures to be completed during the KTE-X19 
conditioning chemotherapy period. 


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7.9.3.2.
KTE-X19 Treatment Period
7.9.3.2.1.
Requirements for Initiating KTE-X19 Infusion 
If any of the following criteria are met prior to the initiation of KTE-X19 infusion, then the 
work-up listed in Section 7.9.4 must be performed to determine the potential cause if there is no 
identified source of infection. 

Temperature > 38 degrees Celsius within 72 hours of KTE-X19 infusion

CRP > 100 mg/L anytime between enrollment to start of KTE-X19 infusion

WBC count or WBC differential concerning for infectious process between enrollment to 
start of KTE-X19 infusion (eg, WBC > 20,000, 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, 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 (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.
Once the above criteria are met, then the subject can proceed with administration of KTE-X19.


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If the KTE-X19 infusion is delayed > 2 weeks, protocol guidelines should be followed regarding 
the need for repeat conditioning chemotherapy. 
7.9.3.2.2.
Hospitalization for KTE-X19 Infusion
Subjects will be hospitalized to receive KTE-X19 infusion and will remain in the hospital for at 
least 7 days to monitor for signs and symptoms of CRS and neurologic events. Post infusion 
monitoring of patients must be for a minimum of 7 days unless otherwise required by country 
regulatory agencies.  Refer to Appendix 4.   
Subjects should not be discharged from the hospital until all KTE-X19-related non-
hematological toxicities resolve to ≤ Grade 1 or return to baseline.  Subjects may be discharged 
with non-critical and clinically stable or improving toxicities (eg, renal insufficiency) even if 
> Grade 1, if deemed appropriate by the investigator.  Subjects should remain in a hospital for 
ongoing KTE-X19-related fever, hypotension, hypoxia, or ongoing neurologic events > Grade 1, 
or if deemed necessary by the investigator.
Subjects should be instructed to remain within proximity of the clinical study site for at least 
4 weeks following KTE-X19 infusion.  Subjects should be advised to refrain from driving and 
engaging in hazardous occupations or activities, such as operating heavy or potentially 
dangerous machinery, for at least 8 weeks following KTE-X19 infusion.  Subjects and their 
family members/caregivers should be educated on potential CRS and neurologic symptoms, such 
as fever, dyspnea, confusion, aphasia, dysphasia, somnolence, encephalopathy, ataxia, or tremor.  
Subjects or their family members/caregivers should be instructed to immediately contact the 
treating investigator or seek immediate medical attention if any of these symptoms develop.
7.9.3.2.3.
KTE-X19 Premedication Dosing
The following pre KTE-X19 infusion medications should be administered approximately 1 hour 
prior to infusion.  Alternatives to the recommendations below should be discussed with the 
medical monitor.   

Acetaminophen 650 mg PO or equivalent

Diphenhydramine 12.5 mg administered either orally or via IV or equivalent
7.9.3.2.4.
KTE-X19 Administration Day 0
KTE-X19 will be administered at one of the dose levels as outlined in Section 3.1.
Refer to the SOA for a listing of study procedures to be completed during the KTE-X19 
treatment period.
Central venous access, such as a port or a peripherally inserted central catheter, is required for 
the administration of KTE-X19.  Catheter care, per institutional guidelines, should be followed. 
Materials and instructions for the thawing, timing, and administering of KTE-X19 are outlined in 


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the IPM.  Vital signs should be measured during and after KTE-X19 treatment (See Section 7.5). 
The IPM must be reviewed prior to administration of KTE-X19. 
Research sites should follow institutional guidelines for the infusion of cell products.  
7.9.4.
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 applicable)

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 performed (prior to the initiation of antimicrobials if clinically 
feasible): 
Blood cultures (aerobic and anaerobic x2 bottles each, cultured for 48 hours) and 
urinalysis 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 )

If a CNS process is suspected, appropriate brain imaging and subsequent LP 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. 


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If the above workup was triggered due to CRP > 100mg/L, CRP should be repeated and if CRP 
continues to increase significantly evaluation should be performed for any other potential 
infectious or inflammatory condition not previously evaluated.  
7.10.
Toxicity Management
To date, the following important risks have been identified with KTE-X19:  CRS, neurologic 
toxicities, infections, hypogammaglobulinemia, and cytopenias.  Refer to the current KTE-X19 
IB for details regarding these events and management guidance for potential risks associated 
with KTE-X19.  Refer to the SOA (Table 3 and Table 4) for the timing of evaluations for CRS 
and neurological related symptoms. 
As the safety experience with KTE-X19 increases, the management guidance may be updated.  
Therefore, it is important to 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 possible complications 
associated with malignancy and cancer treatment.  
7.11.
Laboratory
7.11.1.
Local Lab Analysis  
Assessments listed in Table 2 will be performed at the local laboratory at the time points 
indicated in the SOA.
Table 2.
Clinical Laboratory Parameters
Serum Chemistries
Hematology
Other
Albumin
ALT/GPT
ALP
AST/GOP
Bicarbonate total
Bilirubin totala
BUN or ureaa 
Calcium total
Chloride
Creatinine
Glucose
LDH
Magnesium total
Phosphorus 
Potassium
Sodium
Uric acidb 
CBC with differentialb 
CRP
Ferritin
Pregnancy test
Viral testingc
Abbreviations:  ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea 
nitrogen; CBC, complete blood count; CRP, C-reactive protein; GOP, serum glutamic-oxaloacetic transaminase; GPT, serum 
glutamic-pyruvic transaminase; LDH, lactate dehydrogenase.


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Protocol KTE-Cl9-108 (ZUMA-8) 
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a 
If BUN test cannot be analyzed by the local lab, urea should be analyzed. If total bilimbin is elevated, then direct bilimbin 
should be obtained. 
b 
Per institutional guidelines but must include WBC, neutrophils or ANC, lymphocytes or ALC, hemoglobin, platelets. 
c 
In European Union (EU) sites, viral serologic tests (eg, HIV, Hep B, Hep C) will be can-ied out per institution guidelines and 
EU regulations, unless otherwise required by country regulato1y agencies (refer to Appendix 4 for details), to evaluate for 
active infection (see SOA) 
7.11.2. 
Central Laboratory Analyses 
The following biospecimens will be sent to the centrnl laborato1y(ies) for sample processing, 
accessioning, and distribution to specialty laboratories or Kite: 
• 
Bone manow biopsy and aspirate, nodal biopsy and/or peripheral blood sample for CLL/SLL 
irmnunophenotyping, confinnation of diagnosis and genetic analyses related to CLL/SLL 
prognostic factors 
• 
Peripheral blood for PK (levels of anti-CD19 CART cells), replication-competent retrovirns 
(RCR) testing, and assessment of B-cell aplasia and irmnune reconstitution 
• 
Sennn for phannacodynamics (cytokine levels) and irmnunogenicity testing (development of 
antibodies against KTE-X19) 
• 
CSF or other bodily fluids to monitor for the presence of anti-CD19 CART cells, other 
irmnune cell subsets and for the pm-pose of understanding the mechanism of action and safety 
profile ofKTE-X19 
Samples are obtained at the times indicated in the SOA. Complete instructions regarding sample 
processing and submission to centr·al laborato1y(ies) are provided in the Centi-al Laborato1y 
Manual. 
Eac su ~ect w1 
ave t e ng t to ave t e samp e matena 
estr·oyed at 
any time by contacting the investigator who, in tum, can contact the sponsor. The investigator 
should provide the sponsor with the study and subject number so that the sample can be located 
and desu-oyed. For subjects who withdraw consent, any samples that were not requested to be 
returned or destr·oyed will remain with the sponsor, and any data that may be generated from 
these samples will be entered in the study database. 
Multiple specialty laboratories may be employed for specific analyses, such as baseline/archival 
tumor assessments, confinnation of diagnosis, PK, phannacodynamics, and special safety 
analyses (irmnunogenicity and RCR testing). Refer to the Centr·al Laborato1y Manual for 
instructions regarding submitting such samples to the appropriate laborato1y. 
Centi-al lab irmnunophenotyping of peripheral blood obtained at screening will confmn the 
diagnosis of CLL/SLL. 
CONFIDENTIAL 
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01 September 2021 


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
7.11.2.3. 
Product Characteristics 
Samples of apheresis material or final product will be retained and tested by the sponsor or 
specialty laborato1y for the pmpose of understanding the mechanism of action and safety profile 
ofKTE-X19. 
7.11.2.4. 
Irnmunogenicity 
Irnmunogenicity will be evaluated utilizing a screening enzyme-linked imrnunosorbent assay 
(ELISA) designed to detect antibodies present in sernm that react against the mmine monoclonal 
antibody FMC63, the parent antibody from which the scFv utilized in the KTE-X19 product is 
derived. 
Blood draws for detennination of the presence of anti-FMC63 antibodies using the screening 
assay will be perfo1med at intervals outlined in the SOA or as clinically indicated. 
In the event of a positive result, a qualified confinnato1y assay will be utilized to validate 
positive results observed in the screening assay. Analysis of PK profiles and clinical outcomes in 
CONFIDENTIAL 
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01 September 2021 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 48
01 September 2021
subjects with a positive screening or confirmatory result at baseline or after treatment with 
KTE-X19 will also be conducted to determine the impact of anti-FMC63 antibodies on the 
efficacy and safety of KTE-X19 therapy.
Immunogenicity will also be addressed by a manual review of AE terms indicative of infusion-
related events and anaphylactic reactions among subjects who test positive for these antibodies.
7.11.2.5.
RCR Testing
KTE-X19 comprises T cells transduced with a γ-retroviral vector; hence, there is a theoretical 
risk for RCR developing in exposed subjects.  Additional information is provided in the IB. 
RCR testing will occur at baseline, Month 3, Month 6, and Month 12. Thereafter, samples will 
be collected yearly and held for up to 15 years.  If a subject tests positive for RCR at any time 
point within the first year, samples will continue to be collected and tested yearly for up to 
15 years or as clinically indicated.  Samples for RCR testing are collected as part of the blood 
draw for PBMCs as noted in the SOA.
7.12.
Post-treatment Assessment Period 
After completing KTE-X19 infusion, all subjects will return to the clinic for post-treatment 
follow-up visits and complete the study procedures and assessments per the SOA. 
If a subject progresses before completion of the Month 3 visit, then the following procedures will 
be completed:

Labs (if not already collected at visit in which progressive disease/relapse was confirmed):
Blood draw for PBMC
A PBMC sample should be collected at time of progression and prior to starting 
subsequent anticancer therapy 
Anti-KTE-X19 antibodies 
β-HCG pregnancy test (serum or urine) on all women of childbearing potential

Proceed to the long-term follow-up period (see Section 7.14 and the SOA for details).
Following the initial hospitalization for the KTE-X19 infusion, if the subject is hospitalized with 
any KTE-X19 related AE, the following labs will be collected:

PBMCs on day of admission, then weekly, and on day of discharge

Cytokine levels on day of admission, then weekly, and on day of discharge


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 49
01 September 2021
7.13.
Long-term Follow-up Period
All enrolled subjects will be followed in the long-term follow-up period for safety, survival and 
disease status, if applicable, for up to 15 years.  Subjects will begin the long-term follow-up 
period after they complete the post-treatment assessment period.  Refer to the SOA for a listing 
of study procedures and disease assessments to be completed during the long-term follow-up 
period.  
After completion of at least 3 months of assessments in the KTE-C19-108 study (refer to 
Section 3.7.2), all subjects who received an infusion of KTE-X19 will be given the opportunity 
to transition to a separate LTFU study, KT-US-982-5968. Upon activation of KT-US-982-5968 
at each study site, subjects will be asked to provide informed consent and complete the 
remaining time of their LTFU period. 
Subjects who receive infusion of KTE-X19, but who experience disease progression, will be 
followed in the long term follow up period and undergo the following assessments at the 
timepoints outlined in the SOA:

Survival status

Serious adverse event (SAE) reporting (see Section 9)

Concomitant medications documentation (see Section 6.2)

Subsequent therapy for CLL/SLL (see Section 6.4)

Blood draw for:
PBMCs
 If applicable anti-KTE-X19 antibodies (see SOA, Section 7.14).
Subjects who are enrolled, but do not receive KTE-X19 treatment, will be followed only until 
completion of this study and will undergo the following assessments at the time points outlined 
in the SOA, unless otherwise noted:

Disease assessment per SOC 

Survival status 

Subsequent therapy for the treatment of CLL/SLL (see Section 6.4) 

AE/SAE reporting (refer to Section 9)

Concurrent therapies (see Section 6.2)


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
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Subjects may also be contacted by telephone to confirm survival status and subsequent 
anticancer therapy use.  If the subject fails to return to the clinic for a scheduled protocol-specific 
visit, sites will need to make 2 attempts, using both the telephone and either mail or email 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, then the subject will be considered lost to 
follow-up, and no additional contact will be required. However, sites will be required to continue 
to provide survival status as permitted by local regulations.


KTE-X19 
Kite Pha1m a, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
7.14. 
Schedule of Assessments 
Table 3. 
Schedule of Assessments 
KTE-X19 
Post-treatment Follow-up 
Leukapheresis 
Conditioning 
Administration 
All Post-treatment visits are calculated from 
Procedures 
Sc1·eening 
(Enrollment) 
chemotherapy 
Period • 
Day 0 
:5 approx. 5 
KTE-
:528 days 
days afte1· 
X19 
Day 14 
Day 28 
Month 3 
before 
eligibility 
Infusion 
(± 2 
(±3 
Week8 
(±2 
Day 
enrollment 
confirmation 
D-4 
D-3 
DO 
Dl to 7' 
days) 
days) 
(± 1 week) 
weeks) 
Medical history 
X 
Physical exam • 
X 
X 
x• 
x• 
X 
X 
X 
Weight (plus height at screening) 
X 
X 
Vital signs b 
Xb 
Xb 
X 
X 
X 
X 
ECOG performance status 
X 
Neurnlogical assessment c,k 
X 
X c,k 
QOOC.k 
X c,k 
Disease Assessment 
X 
X 
X 
ECG 
X 
ECHO/MUGA/Chest CT/MRI d 
Xd 
CTorMRi e 
xe 
X 
X 
Local Labs: 
Pregnancy test (senuu or urine) 
X 
xr 
X 
Chem.istiy panel 
X 
X 
X 
X 
X 
X 
X 
X 
CBC w/differential 
X 
X 
X 
X 
X 
X 
X 
X 
LDHf 
X 
x r 
xr 
CRP/fen-itin f 
X 
x r 
xr 
Lumbar puncture/CSF g 
XK 
XK 
Sernlogy (EU sites)1 
xi 
x i 
Centi·al Labs: 
X 
X 
CONFIDENTIAL 
Page 51 
01 September 2021 


KTE-X19 
Protocol KTE-Cl9-108 (ZUMA-8) 
Procedures 
Day 
Blood draw for Anti-KTE-Xl9 
antibodies i 
Blood draw for PBMCs k 
Blood draw for Cytokines k 
Lumbar puncture/CSFg 
Conditioning chemotherapy 
(Fludarabine/Cyclophospham.ide) 
KTE-Xl9 
infusion/Hospitalization 
AEISAEm I Con medsn / 
Subsequent therapy for 
CLUSLL0 / Survival statusP 
CONFIDENTIAL 
Leukapheresis 
Sc1·eening 
(Enrollment) 
:S28 days 
before 
enrollment 
X 
X 
:S approx. 5 
days afte1· 
eligibility 
confirmation 
X 
X 
Conditioning 
chemotherapy 
KTE-X19 
Administration 
Period • 
KTE-
X19 
Infusion 
D-4 
D-3 
DO 
Dl to 7r 
X 
X 
Dl ,4,7k 
xg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 52 
Kite Pha1ma, Inc. 
Amendment 3 
Post-treatment Follow-up 
All Post-treatment visits are calculated from 
Day O 
Day 14 
(± 2 
days) 
xg 
X 
Day 28 
(± 3 
days) 
X 
Week8 
(± 1 week) 
X 
Month 3 
(± 2 
weeks) 
X 
X 
X 
01 September 2021 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
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01 September 2021
Table 4.
Long-term Follow-up Assessments
Procedure 
Long-term Follow-up Periods
Each visit calculated from Day 0 (± 28 day window)
Visit frequency
Month 
6
Month
9
Month
12
Month
15
Month
18
Month
21
Month
24
Month
30
Month
36
Month
42
Month
48
Month
54
Month
60
Month 72, then 
annually 
through Year 
15
Physical exam
X
X
X
X
X
X
X
Disease Assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CT or MRIe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Bone marrow biopsy and 
aspirate h
X h
Local lab:
CBC w/differential
X
X
X
X
X
X
X
X
X
X
X
X
X
Central labs:
Blood draw for PBMC k
X
X
X
X
X
X
X
X
X
Blood draw for Anti-KTE-
X19 antibodies j
X j
Targeted / AE/SAEs m
X
X
X
X
X
X
X
KTE-X19-related SAEs n
Targeted Con Meds n
X
X
X
X
X
X
X
Subsequent therapy for 
CLL/SLLo  / Survival 
statusp
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Footnotes for Table 3 and Table 4
a
Physical exam (Section 7.5):  Subjects with new-onset symptoms related to CRS should undergo physical exam at least daily until symptoms resolve to baseline.   
b
Vital signs (Section 7.5): Includes blood pressure, heart rate, respiration rate, oxygen saturation, and temperature. Height will be collected at screening.  Vitals will be 
monitored during and after the KTE-X19 infusion and as clinically indicated. Weight should be taken on the day of leukapheresis.
c
Neurologic assessment (Section 7.7):  A neurological assessment will be performed at screening, on Day 0 prior to KTE-X19 infusion, on Day 1 and every other day during 
the KTE-X19 hospitalization/observation period, which must last a minimum of 7 days.  
o For new onset of neurologic symptoms (eg, severe headaches, neck stiffness, seizures, encephalopathy, cranial nerve deficits, or any focal neurologic findings on physical 
exam), neurologic assessment should be performed at least daily until symptoms resolve to baseline.  In addition, brain imaging should be considered.  
o Subjects with new onset Grade ≥ 2 neurologic symptoms post-KTE-X19 infusion will have a LP performed to evaluate for potential causes.
d
ECHO/MUGA/Chest CT/MRI:  See Section 7.6 for details.  
CCI


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
e 
CT or MRI disease assessment (Section 7.8.1): Diagnostic quality contrast-enhanced (unless contraindicated) CT (preferred) or MRI of the head, neck, chest, abdomen and 
pelvis must be performed within 28 days before enrollment to confom eligibility. Scans obtained as pa1t of SOC before signing of the informed consent form and within 
56 days can be used for eligibility. If the subject received treatment for CLL or SLL after the eligibili 
intaoes were obtained, then additional baseline ima es must be taken 
after the com letion of CLU SLL treatment and within 28 da s before conditionin o chemothera 
y 
. 
. 
f 
LDH/Fenitin/CRP monitoring: CRP should be collected daily while hospitalized for the KTE-X19 infusion and for subsequent hospitalization for a KTE-X19 related AE. 
If subject develops CRS or neurological symptoms, LDH and Fen-itin should be monitored. 
g 
Lumbar puncture/CSF (Section 7.7): Subjects with new onset Grade c:: 2 neurologic symptoms post-KTE-Xl9 infusion will have a LP performed to evaluate for potential 
causes. A po1t i 
· 
· . 
· 
· 
h 
r 
oo 
raw or anti-
anti odies: Baseline antibody samples to be collected p1-ior to sta1t of leukapheresis. If positive at Month 3, additional samples will be 
collected every 3 months until titers rettun to baseline, are negative, or up to 12 months post-KTE-Xl9 infusion 
k 
Blood draws for PBMCs and cytokines: Dtu-ing the observation period, PBMCs will be collected on Day 7 and cytokines will be collected on Day 1, 4, and 7. 
o 
Following the initial hospitalization for the KTE-X19 infusion, if the subject is hospitalized with any KTE-X19 related adverse events, blood samples for PBMCs and 
cytokines will be collected on day of admission, then weekly, and on day of discharge. 
o 
If the subject experiences a Grade > 3 KTE-Xl 9-related toxicity, such as Grade 3 CRS or netu·ologic event, one additional blood draw for cytokines will be taken at the 
time of the Grade c:: 3 KTE-Xl 9-related toxicity and upon resolution of the event. 
o 
If the subject experiences a Grade >/= 2 CRS (per Lee 2014 c1-ite1-ia). an additional cytokine sample should be drawn at the first onset and first reoccurrence of any c:: 
grade 2 CRS if not already collected on that day. 
o 
PBMC collection will continue after subject expe1-iences disease progression but remains on study 
Viral testing for EU sites: For EU sites, viral serologic tests (eg, HIV, Hep B, Hep C) will be can-ied out per institution guidelines and EU regulations. Testing may be done 
within the 30 days p1-ior to leukapheresis and/or on the day of leukapheresis. 
m 
AE/SAE reporting (Sections 9.2 and Section 9.4): AEs: Aft.er 3 months, only targeted adverse events will be reported in the CRF through 24 months aft.er KTE-X19 infusion or 
disease progression, whichever occtu-s first. SAEs: After 3 months, only targeted se1fous advei-se events will be reported through 24 months after KTE-X19 infusion or disease 
progression, whichevei· occtu-s first, within 24 hotu-s using the SAE Repo1t Fo1m and in the CRF. Targeted adverse events include central ne1u·ological, hematological, infections, 
GVHD, autoinumme disorde1-s, and secondaiy malignancies. Subjects who receive an allogeneic SCT w'ill only be followed for KTE-Xl 9 related sei-ious adve1-se events. 
Reporting of these SAEs will commence at the time the SCT prepai-ative regimen commences through 24 months aft.et· KTE-X19 infusion or disease progression, whichevei· 
occtU'S fo-st, w'ithin 24 h01m using the SAE Repo1t Form and in the CRF. In addition to the above SAE repo1ting requirements, anytime a KTE-Xl9 related SAE occtU'S it will be 
reported w'ithin 24 hotu-s using the SAE Repo1t Form and in the CRF. All deaths that occur from ICF through end of study will be repo1ted in the CRF. 
n 
Concomitant medications reporting (Section 6.2): After 3 months of follow-up, only targeted concomitant medications will be collected for 24 months aftei· KTE-X19 infusion 
or disease progression, whichever occtu-s first. Targeted concomitant medications include gaimuaglobulin, inuuunosuppressive dmgs, anti-infective dmgs, and vaccinations. 
o 
Subsequent therapy for CLL/SLL (Section 6.4): Doctuuentation of subsequent therapy for CLUSLL will continue to be doctuuented while the subject remains on study. 
Subjects may be contacted by telephone. 
p 
Survival Status (Section 7.14): Subjects may be contacted by telephone to confirm smvival status. 
q 
KTE-X19 Administration Pe1iod: refer to Appendix 4 for requirements by c01mtry regulato1y agencies. 
r 
Pregnancy test (sernm or mine): EU only: test to be completed within 7 days p1for to both Letikaphei-esis and Conditioning Cheiuothei-apy for f=les of childbearing potential. 
CONFIDENTIAL 
Page 54 
01 September 2021 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 55
01 September 2021
s
After completion of at least 3 months of assessments in the KTE-C19-108 study, subjects who received an infusion of KTE-X19 will be provided the opportunity to transition 
to a LTFU study (KT-US-982-5968) after providing signed informed consent, to complete the remaining time of their LTFU period.   


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 56
01 September 2021
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 while continuing 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 the IP, study treatment, or other protocol-required 
therapies and must also 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.
Withdrawal of full consent from a study means that the subject does not wish to receive further 
protocol-required therapy, undergo procedures, and continue participating in study follow-up.  
Subject data collected up until withdrawal of consent will be retained and included in the 
analysis of the study.  Publicly available data (death records) can be included after withdrawal of 
consent if local regulations permit.  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 also be asked to 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 at any time prior to 
study completion.
8.1.
Reasons for Removal from Treatment
Reasons for removal from protocol-required IP or procedures include any of the following:

AEs

Subject request

Product not available

Lost to follow-up

Death

Decision by sponsor


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
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01 September 2021
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-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 58
01 September 2021
9.
SAFETY REPORTING
9.1.
Definition of Adverse Events
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 AE(s) observed by the investigator or reported by the subject are recorded in 
the subject’s medical record.  The definition of AE 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.  When recording such 
events, provide descriptions that the pre-existing condition has changed (eg, more frequent 
headaches for a subject with pre-existing headaches or blood pressure is now more increased in a 
subject with pre-existing hypertension).
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, CLL). 
When an AE or SAE is due to the disease under investigation, it is necessary to 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 because of an AE, then the subject should undergo the procedures outlined in the 
Month 3 visit of the SOA. 
9.1.1.
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.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
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01 September 2021
9.1.2.
Abnormal Vital Sign 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 if 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.
9.1.3.
Reporting Abnormal Laboratory Findings
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, or that 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.
An abnormal laboratory test result must be reported as an AE if it is a change from baseline and 
meets any of the following criteria:

Associated with clinical symptoms

Results in a medical intervention (eg, potassium supplementation for hypokalemia or iron 
replacement therapy for anemia) or a change in concomitant therapy

Clinically significant in the investigator’s judgment 
9.2.
Reporting of Adverse Events
The investigator is responsible for reporting all AEs observed by the investigator or reported by 
the subject as follows:


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
CONFIDENTIAL
Page 60
01 September 2021
Table 5.
Reporting Requirements for Adverse Events
Subjects who are enrolled, but do not receive 
KTE-X19 infusion
Subjects who are enrolled and receive KTE-X19 
infusion
Adverse events that occur from enrollment (ie, 
commencement of leukapheresis) through 30 days 
after the last study specific procedure (eg, 
leukapheresis, 
 CSF prophylaxis, 
conditioning chemotherapy) or until initiation of a 
new anticancer therapy, whichever occurs first, will 
be reported

AEs that occur from enrollment (ie, commencement 
of leukapheresis through 3 months after treatment 
with KTE-X19 infusion will be reported

After 3 months, only targeted AEs will be reported 
through 24 months after KTE-X19 infusion or 
disease progression, whichever occurs first, will be 
reported
o
Targeted adverse events include central 
neurological events, hematological events, 
infections, GVHD, autoimmune disorders, and 
secondary malignancies.

Subjects who receive an allogeneic SCT will only be 
followed for KTE-X19-related serious adverse 
events.  See Section 9.4 for reporting requirements.  
See Section 6.2 for concomitant medication and Section 9.4 for SAE reporting requirements.
The investigator must provide the information listed below regarding the AEs being reported: 

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
The AE grading scale used will be the NCI Common Terminology Criteria for Adverse Events 
(CTCAE) version 5.0. A copy of the grading scale can be downloaded from the Cancer Therapy 
Evaluation Program (CTEP) home page (http://ctep.cancer.gov).  CRS events will be reported 
using the grading scale outlined in the IB. 
In reviewing AEs, investigators must assess whether the AE is possibly related to KTE-X19, 
 conditioning chemotherapy, any protocol-required study procedure or 
treatment, disease progression, concurrent disease, concomitant medication, or other. 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 expected to follow reported AEs until stabilization or resolution. If a subject 
begins a new anticancer therapy, the AE reporting period for non-SAEs ends at the time the new 
treatment is started.
CCI
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9.3.
Definition of Serious Adverse Events
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 and seriousness need 
to be independently assessed for each AE recorded on the eCRF.
Disease progression of the malignancy is not considered an AE.  However, signs and symptoms 
of disease progression may be recorded as AEs or SAEs and indicated as being due to disease 
progression with the CRF.  If the malignancy has a fatal outcome before the end of the SAE 
reporting period, then the event leading to the death must be recorded as a SAE with the outcome 
being fatal. 
9.3.1.
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 serious adverse events:

Hospitalization for palliative care or hospice care


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
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
9.4.
Reporting of Serious Adverse Events 
The investigator is responsible for reporting all SAEs observed by the investigator or reported by 
the subject.  Unless otherwise indicated in the table below, all SAEs will be reported within 
24 hours and recorded in the CRF.
Table 6.
Reporting Requirements for Serious Adverse Events
Subjects who screen-fail or who are enrolled, but 
do not receive KTE-X19 infusion
Subjects who are enrolled and receive KTE-X19 
infusion
SAEs that occur from signing of the informed 
consent form through 30 days after the last study 
specific procedure (eg, screening procedure, 
leukapheresis, 
 conditioning 
chemotherapy) or until initiation of a new anticancer 
therapy, whichever occurs first, will be recorded in 
the CRF   

All SAEs that occur from signing of the informed 
consent form through 3 months after the KTE-X19 
infusion or until initiation of another anticancer 
therapy, whichever occurs first

After 3 months, only targeted SAEs will be reported 
through 24 months after KTE-X19 infusion or 
disease progression, whichever occurs first
o
Targeted adverse events include central 
neurological events, hematological events, 
infections, GVHD, autoimmune disorders, and 
secondary malignancies.  

Subjects who receive an allogeneic SCT will only be 
followed for KTE-X19-related serious adverse 
events from the time the SCT preparative regimen 
commences through 24 months after KTE-X19 
infusion or disease progression, whichever occurs 
first 

All SAEs deemed related to KTE-X19 infusion 
regardless of time period

All deaths that occur from signing of the ICF through 
the end of study will be recorded in the CRF
See Section 6.2 for concomitant medication and Section 9.2 for targeted AE reporting requirements.
All SAEs must be submitted to Kite via the eSAE system within 24 hours of the investigator’s 
knowledge of the event.  If the eSAE system is unavailable (eg, system outage), then the SAE 
must be submitted using the SAE Report Form and emailed to the SAE Reporting mailbox: 
. 
Subsequently, all SAEs will be reported in accordance with the EU guidelines, or if applicable, 
as per local reporting guidelines. 
PPD
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Following completion of KTE-C19-108, any relevant information regarding ongoing SAEs must 
be submitted to Kite Pharma within 24 hours of the investigator’s knowledge of the event using 
the hardcopy format SAE Report Form and sent via e-mail to the SAE Reporting mailbox: 
.
9.5.
Reporting Deaths
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 KTE-X19 infusion, regardless of attribution to treatment, requires 
expedited reporting within 24 hours.  Any death occurring after the SAE reporting period 
requires expedited reporting within 24 hours only if it is considered related to treatment. Deaths 
that occur during the protocol-specified AE reporting period that are attributed by the 
investigator solely to progression of underlying leukemia should be recorded as SAEs with the 
preferred term “chronic lymphocytic leukemia” 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 on (eg, after 
autopsy).  Deaths during the post-study survival follow-up due to underlying cancer should be 
recorded only on the Survival Status CRF. 
9.6.
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 or the administration of KTE-X19, whichever is longer. Male 
subjects are recommended to not father a child for 6 months after the conditioning chemotherapy 
dosing or the administration of KTE-X19, whichever is longer.  Refer to Appendix 5 for 
complete list of highly effective contraception methods.
Any pregnancy in a female subject enrolled into the study must be reported, regardless of the 
time after KTE-X19 infusion.  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.  All such pregnancies must be reported to Kite Patient Safety and Pharmacovigilance 
using the Pregnancy Report Form within 24 hours after becoming aware of the pregnancy. 
Information regarding the pregnancy and/or the outcome will be requested by the sponsor. 
PPD


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Pregnancy Report Forms should be reported to Kite Patient Safety and Pharmacovigilance at 
 or fax: 
.
The pregnancy itself is not considered an AE nor is an induced elective abortion to terminate a 
pregnancy without medical reasons. Any premature termination of pregnancy (eg, a spontaneous 
abortion, an induced therapeutic abortion due to complications or other medical reasons) must be 
reported within 24 hours as an SAE. The underlying medical reason for this procedure should be 
recorded as the AE term. Any SAE occurring as an adverse pregnancy outcome after the study 
has been completed must be reported to Kite Patient Safety and Pharmacovigilance.
The pregnant subject or subject partner should receive appropriate monitoring and care until the 
conclusion of the pregnancy. The outcome should be reported to Kite Patient Safety and 
Pharmacovigilance using the Pregnancy Outcome Report Form. If the end of the pregnancy 
occurs after the study has been completed, the outcome should be reported directly to 
Kite Patient Safety and Pharmacovigilance.
Pregnancies of female partners of male study subjects exposed to KTE-X19 or other study drugs 
must also be reported, and relevant information should be submitted to Kite Patient Safety and 
Pharmacovigilance using the pregnancy and Pregnancy Outcome Report Form within 24 hours. 
If the end of the pregnancy occurs after the study has been completed, the outcome should be 
reported directly to Kite Patient Safety and Pharmacovigilance. 
If a lactation case occurs while the female subject is taking protocol-required therapies, the 
lactation case must be reported to Kite Patient Safety and Pharmacovigilance within 24 hours 
after the investigator’s awareness of the event using the Special Situations Reporting Form. In 
addition to reporting a lactation case during the study, investigators should monitor for 
pregnancy and lactation cases throughout the long-term follow-up period. Report the lactation 
case and Special Situations Reporting Forms to Kite Patient Safety and Pharmacovigilance at 
 or fax: 
.
Any lactation case should be reported to the key sponsor contact within 24 hours of the 
investigator’s knowledge of the event.
9.7.
Safety Review Team and Dose-limiting Toxicity
The SRT, that is internal to the study sponsor and in collaboration with at least one study 
investigator, will be specifically chartered to review safety data during the Phase 1 component of 
the study and make recommendations on further study conduct and progression of the study 
based on all data available, including the incidence of KTE-X19 DLT, review of SAEs, and cell 
expansion of KTE-X19.  The SRT safety review outcome will be communicated to the active 
clinical study sites after the SRT safety review meeting.  
DLT is defined as the following KTE-X19-related events with onset within the first 28 days 
following KTE-X19 infusion:
PPD
PPD
PPD
PPD


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Table 7.
DLT Criteria
DLT
Exceptions
All KTE-X19-related Grade 3 
non-hematologic toxicities lasting 
for > 7 days 
All KTE-X19-related Grade 4 
non-hematologic toxicities 
regardless of duration 

Aphasia/dysphasia or confusion/cognitive disturbance which resolves to 
at least Grade 1 or baseline within 2 weeks and to at least baseline 
within 4 weeks.

Fever Grade 3 or 4

Immediate hypersensitivity reactions occurring within 2 hours of 
KTE-X19 infusion (related to KTE-X19 infusion) that are reversible to a 
Grade 2 or less within 24 hours of KTE-X19 infusion with standard 
therapy

Renal toxicity which requires dialysis for ≤ 7 days 

Intubation for airway protection if ≤ 7 days

Tumor lysis syndrome (TLS) including associated manifestations 
attributable to TLS (eg, electrolyte abnormalities, renal function, 
hyperuricemia)

Grade 3 transaminase, alkaline phosphatase, bilirubin or other liver 
function test elevation, provided there is resolution to ≤ Grade 2 within 
14 days

Grade 4 transient serum hepatic enzyme abnormalities provided there is 
resolution to ≤ Grade 3 within < 72 hours

Hypogammaglobulinemia Grade 3 or 4

Grade 3 nausea and/or anorexia
Grade 4 hematologic toxicity 
lasting more than 30 days if not 
attributable to underlying disease
Lymphopenia
CRS will be graded according to a revised grading system {Lee 2014}. AEs attributed to CRS 
will be mapped to the overall CRS grading assessment for the determination of DLT. Consistent 
with non-CRS toxicities, all occurrences of Grade 3 CRS of duration > 7 days and all 
occurrences of Grade 4 CRS are considered DLTs, other than occurrences of CRS due to the 
exceptions listed above.
A 6 + 3 dose escalation/de-escalation plan was used in the initial Phase 1 DLT evaluation period, 
Cohort 1 and Cohort 2. Cohort 3 will enroll and dose 3 subjects at a dose of 1x106 anti-CD19 
CAR T cells/kg. This is an exploratory cohort. No additional dose levels will be evaluated. 
A 3 + 3 design will be used for Cohort 4 SRT evaluation. The initial target dose to be evaluated 
will be 1 x 106 anti-CD19 CAR T cells/kg (Starting Dose).  An additional target dose that may be 
evaluated in Cohort 4 is 2 x 106 anti-CD19 CAR T cells/kg (Escalation Dose).  Escalation to a 
dose cohort will depend on review of all data available including the number of DLTs within a 
dose cohort among DLT-evaluable subjects (see Section 10.6).  Three to 12 subjects will be 
enrolled and dosed in Cohort 4.  If ≤1 subjects develops a DLT, enrollment will continue to 
Cohort 4 Escalation Dose. The following table provides details for the dose escalation/de-
escalation plan based on the incidences of DLTs for Cohort 1 and Cohort 2.


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Table 8.
DLT Evaluation Cohort 1 and Cohort 2
Dose Cohort 1 and 2
If incidence of DLT*
Then
< 2 out of 6
Proceed to Dose Level 1 (2 x 106 
anti-CD19 CAR T cells/kg) 
= 2 out of 6
enroll 3 more subjects at current dose 
(Dose Level 0)
< 3 out of 9
Proceed to Dose Level 1 (2 x 106 
anti-CD19 CAR T cells/kg) 
1 x 106 anti-CD19 CAR T cells/kg 
(initial dose) 
(Dose Level 0)
≥ 3
Proceed to Dose Level -1 (0.5 x 106 
anti-CD19 CAR T cells/kg) 
< 2 out of 6
Dose Level -1 is the MTD
= 2 out of 6
Enroll 3 more subjects at current 
dose (Dose Level -1)
< 3 out of 9
Dose Level -1 is the MTD
0.5 x 106 anti-CD19 CAR T cells/kg 
(Dose Level -1)
≥ 3
Additional dose levels lower than 
Dose Level -1 may be explored
< 2 out of 6
Dose Level 1 is the MTD
= 2 out of 6
Enroll 3 more subjects at current 
dose (Dose Level 1)
< 3 out of 9
Dose Level 1 is the MTD
2 x 106 anti-CD19 CAR T cells/kg 
(Dose Level 1)
≥ 3
Dose Level 0 is the MTD
The following table provides details for the dose escalation plan based on the incidences of 
DLTs for Cohort 4.
Table 9.
DLT Evaluation Cohort 4
Dose Cohort 4
If incidence of DLT*
Then
0 out of 3
Proceed to Dose Level 1
1 out of 3
Enroll 3 more subjects at current 
dose (Dose Level 0)
> 1 out of 3 or > 1 out of 6
No MTD is found for cohort 4
1 x 106 anti-CD19 CAR T cells/kg 
(initial dose) 
(Dose Level 0)
1 out of 6
Proceed to Dose Level 1
0 out of 3
Dose Level 1 is the MTD
1 out of 3
Enroll 3 more subjects at the current 
dose level (Dose Level 1)
> 1 out of 3 or >1 out of 6
Dose Level 0 is the MTD
2 x 106 anti-CD19 CAR T cells/kg 
(Dose Level 1)
1 out of 6
Dose Level 1 is the MTD
Abbreviations: DLT, dose limiting toxicities; MTD, maximum tolerated dose  
*DLT evaluable subjects


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For the safe dose level identified, additional subjects will be enrolled and dosed so that the 
cohort will have up to 9-12 subjects to further evaluate the safety profile.  
9.8.
Criteria to Pause Enrollment
Study enrollment will be paused in Phase 1 following any grade 5 adverse event that occurs 
within 30 days of KTE-X19 infusion regardless of attributions. 
In the event that the enrollment is paused after the pausing criteria have been met, overall 
assessment of the benefit/risk ratio will be conducted. If the overall assessment of the benefit/risk 
ratio is favorable, the study can resume enrollment. Restart of the study may require prior 
approval if required by applicable regulatory requirements or mandated by in country Regulatory 
Agency (see Appendix 4).


KTE-X19 
Protocol KTE-Cl9-108 (ZUMA-8) 
10-
STATISTICAL CONSIDERATIONS 
10.1. 
Hypothesis 
No fonnal hypothesis testing for this phase 1 study. 
10.2. 
10.2.1. 
Study Endpoints 
Primary Endpoints 
Incidence ofDLTs in subjects ti·eated with KTE-X19 (Section 9.7) 
10.2.2. 
Secondary Endpoints 
• 
Incidence of AEs 
• 
Levels of anti-CD19 CART cells in blood 
Kite Pha1m a, Inc. 
Amendment 3 
• 
Overall Response Rate (ORR): The incidence of a CR, CRi, or PR per investigator review as 
defined by IWCLL 2018 criteria (Appendix 3). 
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Protocol KTE-Cl9-108 (ZUMA-8) 
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10.3. 
Sample Size Considerations 
For Cohort 1 and Coho1i 2, the study enrolled and dosed a total of 9 subjects with no DLT 
observed. The anticipated enrollment for Coho1i 3 and Coho1i 4 is up to approximately 
18 subjects, leaving the total up to 27 subjects enrolled and dosed in this study. 
Coho1i 3 will enroll and dose 3 subjects in an explorato1y coho1i . No additional subjects will be 
enrolled or dose levels evaluated. 
Coho1i 4, the SRT will review all data available including safety and efficacy data after 3 to 6 
subjects enrolled and dosed at each dose level (see Section 10.6) have had the oppo1iunity to be 
followed for 28 days after the KTE--X19 infusion. If the lymphodepleting regimen and one or 
more KTE-X19 doses evaluated in Phase 1 are detennined to be safe based on all data available, 
including overall safety profile, the incidence of DLT, and cell expansion ofKTE-X19, up to 
approximately total of 12 subjects may be enrolled and dosed in the dose cohort to fuiiher 
evaluate safety. The maximum number of subjects, including those enrolled and dosed in 
Coho1i 4 will be approximately 15 subjects. 
10.4. 
Access to Individual Subject Treatment Assignments 
This is a single-aim, open-label 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 plan, SRT chaii er, and Trial Integrity Document. 
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Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
10.5. 
Interim Analysis and Early Stopping Guidelines 
During the study, SRT meetings will review the safety and PK data after 3-6 subjects had been 
dosed at the level of 1 x or 2 x 106 anti-CD19 CAR T cells/kg and followed for 28 days. 
The SRT will review the safety data and make recommendations on fmiher study conduct and 
progression of the study as outlined in Section 9. 7. 
The sponsor reserves the right to conduct additional analyses of safety and efficacy for 
regulato1y interaction pmposes. If conducted, no fonnal hypothesis testing will be perfonned in 
such analyses. 
10.6. 
Analysis Subsets 
DLT-evaluable set: All subjects treated with the target KTE-X19 dose and followed for at least 
28 days, or who received a dose ofKTE-X19 lower than the target dose but experienced a DLT 
during the 28-day post infusion period, up to the time at which a dose level has been evaluated 
for DLT and deemed safe. Additional Phase 1 subjects enrolled and treated subsequently for the 
pmpose of assessment of the overall safety in the same dose level or a lower dose level will not 
be considered as part of the DLT-evaluable set, and DLT will not be assessed for such subjects. 
Safety analysis set: The safety analysis set is defined as all subjects treated with any dose of 
KTE-X19. 
Full analysis set (FAS): The full analysis set will consist of all enrolled subjects and may be 
used for the sllllllnaiy of subject disposition and subject listings of deaths. 
Modified intent-to-treat (mITT) set: The modified intent-to-treat set will consist of subjects 
enrolled and treated with KTE-X19 and with radiographically measurable disease-
rior to administration of conditionin 
10.7. 
Planned Method of Analysis 
All the analyses will be descriptive. The final analysis will occur when all subjects have 
completed the study. 
10.7.1. 
ORR 
The incidence of objective response and exact 2-sided 95% confidence intervals will be 
generated. - -
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Protocol KTE-Cl9-108 (ZUMA-8) 
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10.7.8. 
Safety 
Subject incidence rates of ti·eatment-emergent adverse events (TEAEs), defined as adverse 
events with onset on or after the KTE-X19 infusion, will be summarized. TEAEs including all, 
serious, fatal, CTCAE version 5.0 Grade 3 or higher and u-eatment-related AEs will be tabulated 
by prefened tenn and/or system organ class. CTCAE grade changes in safety laborato1y values 
will be summarized with descriptive statistics. The incidence of concomitant medications will be 
summarized. 
Tables and/or nairntives of deaths and ti·eatment related SAEs will be provided. 
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11.
REGULATORY OBLIGATIONS 
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki

Applicable International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) 
Guidelines

Applicable laws and regulations
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 sites respective Independent Review Board 
/Independent Ethics Committee (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 within all material that is submitted to the key 
sponsor contact.  The following rules are to be applied.

Subjects will be identified by a unique identification number.

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 identification 
number, initials, and year of birth (as per their local reporting requirements for both initials and 
year of birth).


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Protocol KTE-C19-108 (ZUMA-8)
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Per country-specific regulations and 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 Pharma, Inc. under the following criteria:

Is a recognized expert in the disease setting

Provided significant contributions to the design or analysis of study data

Participate in the study and enrolled a high number of eligible subjects


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Protocol KTE-C19-108 (ZUMA-8)
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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 are to be submitted to the key sponsor contact.
Both Kite Pharma, Inc. 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 regarding either the trial completion or early 
termination and provide the CRO with a copy of the correspondence.
Kite Pharma, Inc. reserves the unilateral right, at its sole discretion, to determine whether to 
manufacture KTE-X19 and provide it to sites and subjects after the completion of the study.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
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13.
STUDY DOCUMENTATION AND ARCHIVING
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated.  The 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.  Examples of such source documents may include, but are not limited to, 
hospital records and patient charts, laboratory, pharmacy, radiology records, subject diaries, 
microfiches, correspondence, and death registries.  Case report form entries may be considered 
as source data if the site of the original data collection is not available.  However, the use of the 
CRFs as source documentation is not recommended as a routine practice.
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, health authorities, and IRB/IECs.  The filing system will 
include at minimum:

Subject content including ICFs and subject identification lists

Protocols and protocol amendments, Investigator’s Brochure, 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 Pharma, Inc. and the investigator.  If storage is no longer available to 
archive source documents, or if source documents must be moved to an alternative location, the 
research staff should notify the key sponsor contact prior to shipping the documents.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
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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 must also assure that subject confidentially is respected.
The monitor is responsible for source document verification of CRF data at regular intervals 
during the study. Protocol adherence and 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 (Study Documentation and Archive).
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 therapies should be identified by tradenames.  For further details surrounding 
the completion of CRFs, please refer to the CRF completion guidelines.


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Protocol KTE-C19-108 (ZUMA-8)
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15.
PUBLICATION
Authorship of publications from data generated in ZUMA-8 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 that 
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 Pharma, 
Inc. for review and approval.  The study contract among the institution, principal investigator, 
and Kite Pharma, Inc. or its delegate will outline the requirements for publication review.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
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16.
COMPENSATION
Kite Pharma, Inc. will provide compensation for study-related illness or injury pursuant to the 
information outlined in the injury section of the ICF. 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
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17.
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Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
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Kite Pharma, Inc.
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Amendment 3
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B-cell lymphoma: reduced CD20 expression is associated with an inferior 
survival. Blood 2009b;113 (16):3773-80.
Jones JA, Mato AR, Wierda WG, Davids MS, Choi M, Cheson BD, et al. Venetoclax for chronic 
lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a 
multicentre, open-label, phase 2 trial. Lancet Oncol 2018;19 (1):65-75.
Klebanoff CA, Khong HT, Antony PA, Palmer DC, Restifo NP. Sinks, suppressors and antigen 
presenters: how lymphodepletion enhances T cell-mediated tumor 
immunotherapy. Trends Immunol 2005;26 (2):111-7.
Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, et al. B-cell 
depletion and remissions of malignancy along with cytokine-associated toxicity in 
a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 
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et al. Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma and Indolent B-
Cell Malignancies Can Be Effectively Treated With Autologous T Cells 
Expressing an Anti-CD19 Chimeric Antigen Receptor. J Clin Oncol 2015;33 
(6):540-9.


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Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
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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.
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of multiple myeloma. Am J Clin Pathol 2004;121 (4):482-8.
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Improves T Cell Number and Function in CLL Patients. J Clin Invest 2017;127 
(8):3052-64.
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Ibrutinib Therapy Discontinuation and Outcomes in Patients With Chronic 
Lymphocytic Leukemia. JAMA Oncol 2015;1 (1):80-7.
Mato AR, Hill BT, Lamanna N, Barr PM, Ujjani CS, Brander DM, et al. Optimal Sequencing of 
Ibrutinib, Idelalisib, and Venetoclax in Chronic Lymphocytic Leukemia: Results 
from a Multicenter Study of 683 Patients. Ann Oncol 2017;28:1050-6.
Mato AR, Nabhan C, Barr PM, Ujjani CS, Hill BT, Lamanna N, et al. Outcomes of CLL patients 
treated with sequential kinase inhibitor therapy: a real world experience. Blood 
2016;128 (18):2199-205.
Mato AR, Nabhan C, Thompson MC, Lamanna N, Brander DM, Hill B, et al. Toxicities and 
outcomes of 616 ibrutinib-treated patients in the United States: a real-world 
analysis. Haematologica 2018;103 (5):874-9.
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lymphocyte-associated antigen expressed on normal, mitogen-activated, and 
malignant B lymphocytes. J Immunol 1983;131 (1):244-50.
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Med 2017;377 (26):2531-44.
Nicholson IC, Lenton KA, Little DJ, Decorso T, Lee FT, Scott AM, et al. Construction and 
characterisation of a functional CD19 specific single chain Fv fragment for 
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fludarabine and cyclophosphamide combination regimen in chronic lymphocytic 
leukemia. J Clin Oncol 2001;19 (5):1414-20.


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Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
Amendment 3
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Olejniczak SH, Stewart CC, Donohue K, Czuczman MS. A quantitative exploration of surface 
antigen expression in common B-cell malignancies using flow cytometry. 
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receptor T cells persist and induce sustained remissions in relapsed refractory 
chronic lymphocytic leukemia. Sci Transl Med 2015;7 (303):303ra139.
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with Relapsed/Refractory Chronic Lymphocytic Leukemia after Ibrutinib 
Discontinuation Outside Clinical Trials: A Single Institution Experience. Blood 
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Protocol KTE-C19-108 (ZUMA-8)
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Previously Treated with Ibrutinib [Abstract]. Blood (ASH Annual Meeting 
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KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-108 (ZUMA-8)
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18.
APPENDICES
Appendix 1.
Sponsor and Investigator Signature Page
Appendix 2.
Binet and Rai Staging Systems for the Classification of CLL
Appendix 3.
IWCLL 2018 Response Criteria and Disease Response Assessment
Appendix 4.
Country specific regulatory agency requirements
Appendix 5.
Birth control methods which may be considered as highly effective1


KTE-Xl9 
Protocol KTE-Cl9-108 (ZUMA-8) 
Appendix 1. 
Sponsor and Investigator Signature Page 
KITE PHARMA, INC. 
2400 BROADWAY 
SANTA MONICA, CA 90404 
STUDY ACKNOWLEDGMENT 
Kite Phruma, Inc. 
Amendment3 
A Phase 1 Multicenter Study Evaluating the Safety and Tolerability ofKTE-X19 in Adult Subjects 
with Relapsed/Refracto1y Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma 
Amendment 3.0, 01 September 2021 
This protocol has been approved by Kite Phanna, Inc. The following signature documents this 
app~OVal. 
- ~.._P_DP_u_Sl_o_•d_b_y, ___ __. _______ _ 
Kite Medical Monitor Name (Printed) 
September 9, 2021 I 12: 17:52 AM PDT 
Date 
Signature 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices, and I agree that it contains all necessa1y 
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 effo1i to complete the study within the time 
designated. 
I agree to comply with the International Council for Ha1monisation of Technical Requirements 
for Phaim aceuticals for Human Use (ICH) Haim onised Tripaiiite 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 info1mation provided by 
Kite Pha1ma, Inc. I will discuss this material with them to ensure that they are fully info1med 
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 pa1iner, and dependent children) 
at the sta1i of the study and for up to one year after the study is completed. 
I agree to ensure that the confidential info1mation 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 Phaim a, Inc. 
Principal Investigator Naine (Printed) 
Signature 
Date 
Site Number 
CONFIDENTIAL 
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01 September 2021 


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Appendix 2.
Binet and Rai Staging Systems for the Classification of CLL
Binet
Stage
Lymph Node Areas
Hemoglobin
< 10 g/dL
Platelet
< 100 × 109/L
A
< 3
No
No
B
≥ 3
No
No
C

Either present
Rai
Stage
Lymphocytosis
Lymph Node 
Enlargement
Spleen/Liver 
Enlargement
Hemoglobin 
< 11 g/dL
Platelet
< 100 × 109/L
0
Yes
No
No
No
No
I
Yes
Yes
No
No
No
II
Yes

Yes
No
No
III
Yes


Yes
No
IV
Yes



Yes


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Appendix 3.
IWCLL 2018 Response Criteria and Disease Response Assessment
The determination of CLL response and progression will be based on standardized 
International Workshop on CLL (IWCLL) 2018 criteria. These criteria will be used to assess 
SLL.
Appendix Table 1.
IWCLL 2018 Response Criteria
Parameter
CR
PR
PD
Group A (indicating tumor load)
Lymphadenopathy1
none ≥ 1.5 cm
decrease ≥ 50%
increase by ≥ 50% or 
new lymph nodes 
≥ 1.5 cm
Hepatomegaly
none
decrease ≥ 50%
Increase by ≥ 50 %
Splenomegaly
none
decrease ≥ 50%
Increase by ≥ 50 %
Blood lymphocytes
< 4000/µL
decrease of ≥ 50% from 
baseline
Increase by ≥ 50% over 
baseline2 to ≥ 5000/µL
Group B (indicating function of the hematopoietic system)
Platelet count
≥ 100,000/µL
≥ 100,000/µL or increase by 
≥ 50% from baseline
Decrease by ≥ 50% 
from baseline due to 
CLL
Hemoglobin
≥ 11 g/dL
≥ 11 g/dL or increase by 
≥ 50% from baseline
Decrease by ≥ 2 g/dL
Bone Marrow
Normocellular for age, no 
increase in CLL lymphocytes, 
no clonal B-lymphoid nodules3
CLL cells or clonal B-
lymphoid nodules present
Increase in CLL cells by 
≥50% on successive 
biopsies
1
Assessed as sum of the products of up to 6 lymph nodes
2
Subjects with treatment-related lymphocytosis should not be rated PD and remain on study treatment if other criteria for 
progressive disease are absent.
3
In case of B-lymphoid nodules assessment is recommended to clarify if the population is clonal—if not, subjects can be 
assessed as CR/CRi if all other criteria are fulfilled.


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-108 (ZUMA-8) 
Amendment3 
Appendix Table 2. 
Disease Response Assessment 
Overall Disease 
Criteria in Appendix Table 1 
Additional Criteria 
Response 
CR 
All criteria in Group A and B 
No disease related symptoms should be 
present, neutrophil count:?: 1500/µL 
CRi 
All criteria for CR are met except with 
platelet count < l 00,000/µl, hemoglobin < 
11 g/ dL or neutrophil count < 1500/ µL 
PR1 
At least 1 criteria from Group A and 1 
If only one criterion is abno1mal at baseline 
from Group B must be fulfilled. 
from Group A or B, only that criterion must 
improve. 
SD 
Failure to achieve a PR and absence of 
PD 
PD 
Presence of at least 1 of the criteria from 
Constitutional symptoms alone do not define 
Group A or Group B 
PD. A bone man-ow biopsy should be 
perfonned to confum progression if blood 
count changes are the only evidence of 
progression. 
Nodular PR is defined as a CR/CRi with the presence of nodules of clonal lymphocytes in the bone man-ow and will be 
considered a PR for the purposes of this study. 
CONFIDENTIAL 
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Appendix 4.
Country specific regulatory agency requirements 
France and Italy
The post-infusion monitoring of subjects, described in Section 7.9.3.2.2. of this protocol, will be 
extended by monitoring on Day 8, Day 9, and Day 10, according to procedures outlined in 
Table 3, column “KTE-X19 Administration Period, D1 to 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 7.5), blood draw for chemistry panel 
with CRP, blood draw for CBC w/differential, and neurological assessment (see Section 7.7). 
Any observed toxicity will be managed according to Section 7.10 of this protocol.
Germany
The post-infusion monitoring of subjects, described in Section 7.9.3.2.2. of this protocol, will be 
extended by monitoring on Day 8, Day 9, and Day 10, according to procedures outlined in 
Table 3, column "KTE-X19 Administration Period, D 1 to 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 7.5), blood draw for chemistry panel 
with CRP, blood draw for CBC w/differential, and neurological assessment (see Section 7.7). 
Any observed toxicity will be managed according to Section 7.10 of this protocol.


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Appendix 5.
Birth control methods which may be considered as highly effective1
For the purpose of this guidance, methods that can achieve a failure rate of less than 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 ovulation2:
oral
intravaginal
transdermal

progestogen-only hormonal contraception associated with inhibition of ovulation2:
oral 
injectable
implantable3

intrauterine device (IUD)3

intrauterine hormone-releasing system (IUS)3

bilateral tubal occlusion3

vasectomized partner 3,4

sexual abstinence5
1
2014 clinical trial facilitation and coordination group contraception guidance
2
Hormonal contraception may be susceptible to interaction with the investigational product, which may reduce the efficacy of 
the contraception method
3
Contraception methods that in the context of this guidance are considered to have low user dependency.
4
Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the woman 
of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical 
success
5
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 the preferred and usual lifestyle of the 
subject. 

SAP_001.pdf: 
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Company Code:
KTE-X19
USAN Name:
Brexucabtagene Autoleucel
Product Name:
KTE-X19
Version Number:
2.0
Release Date:
21 January 2021
Replaces Previous 
Version(s):
Version 1: dated 25 June 2019
CONFIDENTIALITY NOTICE
This document contains confidential information of Kite Pharma Inc.  This document must not be 
disclosed to anyone other than the site research staffs 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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KTE-C19-108 (ZUMA-8) Statistical Analysis Plan
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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................................................2
LIST OF TABLES..........................................................................................................................................................3
LIST OF FIGURES ........................................................................................................................................................3
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.................................................................................4
1.
INTRODUCTION..................................................................................................................................................6
2.
OBJECTIVES.........................................................................................................................................................7
3.
STUDY DESIGN...................................................................................................................................................8
3.1.
Overview ...................................................................................................................................................8
3.2.
Hypothesis ...............................................................................................................................................10
3.3.
Sample Size Consideration......................................................................................................................10
3.4.
Statistical Assumptions ...........................................................................................................................10
4.
THE INDEPENDENCE OF SUBJECT RESPONSES WILL BE ASSUMED. STUDY ENDPOINTS 
AND COVARIATES...........................................................................................................................................11
4.1.
Endpoints.................................................................................................................................................11
4.1.1.
Primary ..................................................................................................................................11
4.1.2.
Secondary ..............................................................................................................................11
4.2.
Covariates................................................................................................................................................11
4.2.1.
Baseline Covariates ...............................................................................................................12
5.
DEFINITIONS .....................................................................................................................................................13
5.1.
General ....................................................................................................................................................13
5.2.
Safety.......................................................................................................................................................13
5.3.
Efficacy....................................................................................................................................................15
6.
ANALYSIS SUBSETS ........................................................................................................................................16
6.1.
DLT Evaluable Set ..................................................................................................................................16
6.2.
All Treated Subjects ................................................................................................................................16
6.3.
Safety Analysis Set..................................................................................................................................16
6.4.
Full Analysis Set......................................................................................................................................16
6.6.
Subgroup Analysis Sets...........................................................................................................................16
7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES....................................................................17
7.1.
Safety Interim Analysis ...........................................................................................................................17
7.2.
Assessment of Criteria to Pause Enrollment ...........................................................................................17
7.3.
Access to Aggregate and Subject-level Data and Individual Subject Treatment Assignments ..............17
8.
DATA SCREENING AND ACCEPTANCE.......................................................................................................18
8.1.
General Principles ...................................................................................................................................18
8.2.
Electronic Transfer and Archiving of Data .............................................................................................18
8.3.
Handling of Missing and Incomplete Data..............................................................................................18
8.3.1.
Efficacy..................................................................................................................................18
8.3.2.
Safety.....................................................................................................................................18
8.4.
Detection of Bias .....................................................................................................................................19
8.5.
Outliers ....................................................................................................................................................19
8.6.
Distributional Characteristics ..................................................................................................................19
8.7.
Validation and Configuration Management ............................................................................................19
CCI
CCI
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KTE-X19 
Kite Pha1ma, Inc. 
KTE-C19-108 (ZUMA-8) Statistical Analysis Plan 
9. 
STATISTICAL METHODS OF ANALYSIS ...................................................................................................... 20 
9.1. 
9.2. 
9.3. 
9.4. 
9.5. 
9.6. 
9.7. I 
9.10. 
9.11. 
General Principles ................................................................................................................................... 20 
Subject Accountability ............................................................................................................................ 20 
Impo1tant Protocol Deviations ................................................................................................................ 20 
Demographic and Baseline Characteristics ............................................................................................. 20 
Efficacy Analyses .................................................................................................................................... 20 
9.5.1. 
ORR ....................................................................................................................................... 21 
Safety Analyses ....................................................................................................................................... 22 
9.6.1. 
AEs ........................................................................................................................................ 22 
9.6.2. 
Procedmes and Concomitant Medications ............................................................................ 23 
9.6.3. 
Laborato1y Test Results ......................................................................................................... 23 
9.6.4. 
Anti-KTE-Xl9 Antibodies .................................................................................................... 23 
9.6.5. 
RCR ....................................................................................................................................... 23 
9 .6.6. 
Exposme to Study Treatment ................................................................................................ 24 
9.6. 7. 
Exposme to Concomitant Medications and Procedmes ........................................................ 24 
Product Characteristics ............................................................................................................................ 24 
Subsequent Anti-Cancer Therapy ............................................................................................................ 24 
Duration Meti·ics ...................................................................................................................................... 25 
10. CHANGES FROM PROTOCOL-SPECIFIED ANALYSES .............................................................................. 26 
11. REFERENCES ..................................................................................................................................................... 27 
12. APPENDICES ...................................................................................................................................................... 28 
Appendix 1. 
Appendix 2. 
Appendix 3. 
Appendix 4. 
Table 1. 
Table 2. 
Table 3. 
Table 4. 
Table 5. 
Table 6. 
Figme 1. 
CONFIDENTIAL 
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates ........... 29 
IWCLL 2018 Response Criteria and Disease Response Assessment.. .................................... 30 
Derivation of Time to Event Endpoints and Last Date Known to Be Alive ........................... 32 
Binet and Rai Staging Systems for the Classification of CLL ................................................ 35 
LIST OF TABLES 
Imputation Rules for Pa1tial or Missing Strut Dates ................................................................ 29 
IWCLL 2018 Response Criteria .............................................................................................. 30 
Disease Response Assessment. ................................................................................................ 31 
Analysis of DOR for Treated Subjects with Objective Response ........................................... 32 
Analysis of PFS for Treated Subjects ...................................................................................... 32 
Analysis of OS for Treated Subjects ....................................................................................... 33 
LIST OF FIGURES 
Study Schema for Study KTE-C19-108 .................................................................................... 9 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
ADaM
Analysis data model
AE
Adverse event
ANC
Absolute neutrophil count
ALT
Alanine transaminase
AST
Aspartate aminotransferase
ASCT
Autologous stem cell transplant
CAR
Chimeric antigen receptor
CLL
Chronic lymphocytic leukemia
CNS
Central nervous system
CR
Complete response
CRF
Case report form
CRi
Complete response with incomplete hematopoietic recovery
CRS
Cytokine release syndrome
CTCAE
Common terminology criteria for adverse event
DLT
Dose-limiting toxicity
ECOG
Eastern Cooperative Oncology Group
EOP1
End of phase 1
FAS
Full analysis set
HLGT
High-level group term
IWCLL
International Workshop on Chronic Lymphocytic Leukemia
MedDRA
Medical Dictionary for Regulatory Activities
MRD
Minimal residual disease
MRD-
Minimum residual disease negative
MST
MedDRA search term
MTD
Maximum tolerated dose
OS
Overall survival
ORR
Objective response rate
PD
Progressive disease
PR
Partial response
RCR
Replication-competent retrovirus
R/R
Relapsed/Refractory 
r/r CLL
Relapsed/Refractory chronic lymphocytic Leukemia
SAE
Serious adverse event
SAP
Statistical analysis plan
SCT
Stem cell transplant
SD
Stable disease
SDTM
Study data tabulation model 
SLL
Small lymphocytic lymphoma
SMQ
Standardized MedDRA query 


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KTE-C19-108 (ZUMA-8) Statistical Analysis Plan
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SOC
System organ class
SRT
Safety review team
TEAE
Treatment-emergent adverse event
ULN
Upper limit of normal
WHO
World Health Organization


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1.
INTRODUCTION
This statistical analysis plan (SAP) provides the pre-specification and details for the statistical 
analyses to support the protocol KTE-C19-108 entitled “A Phase 1 Multicenter Study Evaluating 
the Safety and Tolerability of KTE-X19 in Adult Subjects with Relapsed/Refractory Chronic 
Lymphocytic Leukemia and Small Lymphocytic Lymphoma” Amendment 2 dated 27 May 2020. 
The scope of this plan includes the end of phase 1 (EOP1) and final analyses. 


KTE-X19 
Kite Pha1ma, Inc. 
KTE-C19-108 (ZUMA-8) Statistical Analysis Plan 
2_ 
OBJECTIVES 
The prirmuy objective of this study is to evaluate the safety and tolerability of KTE-X19 in 
subjects with relapsed or refracto1y (r/r) chronic lymphocytic leukemia (CLL) and small 
lymphocytic lymphoma (SLL). 
Secondaiy objectives ai·e to characterize the safety profile and anti-KTE-X19 antibodies, and to 
evaluate the efficacy ofKTE-X19 as measmed by the objective response rate (ORR) per 
investigator review in subjects with r/r CLL treated with KTE-X19. Efficacy analysis for ORR 
will be perfo1med only for the selected safe dose coho1t. 
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3.
STUDY DESIGN
3.1.
Overview
Study KTE-C19-108 is a Phase 1, multicenter, open-label study evaluating the safety and 
tolerability of KTE-X19 in adult subjects with r/r CLL and SLL. The trial will be separated into 
2 different stages (Cohort 1 and 2 in the first stage and Cohort 3 and 4 in the second stage).
The anticipated total number of enrolled and treated subjects in this study is up to approximately 
27 subjects (estimated based on actual enrollment in Cohort 1 is 6 and Cohort 2 is 3 during 
Protocol Amendment 2). 
During the first stage of the study, subjects with r/r CLL will be enrolled using a 6+3 study 
design into cohorts described below:

Cohort 1: Up to 9 subjects will be enrolled at 1x106 anti-CD19 chimeric antigen receptor 
(CAR) T cells/kg. Decision to enroll in Cohort 2 will be based on incidence of dose limiting 
toxicity (DLT) in Cohort 1. 

Cohort 2: Up to 9 subjects will be enrolled at 2x106 anti-CD19 CAR T cells/kg. 
In the second stage (Protocol Amendment 2), subjects with r/r CLL and SLL will be enrolled 
into Cohort 3 and 4 as described below:

Cohort 3: Three (3) subjects with r/r CLL and SLL with ≤ 1% malignant cells in peripheral 
blood or absolute lymphocyte count (ALC) < 5,000 cells/µL will be enrolled and dosed with 
KTE-X19 at a dose of 1x106 anti-CD19 CAR T cells/kg. Subjects must have received at least 
2 prior lines of treatment, one of which must include a BTK inhibitor. This is an exploratory 
cohort. No additional dose levels will be evaluated.

Cohort 4: Up to approximately 15 subjects with r/r CLL who have been previously treated 
with at least two prior lines of therapy and are receiving ibrutinib as a single agent, or 
ibrutinib in combination with anti-CD20 antibodies, BCL-2 inhibitors, and PI3k inhibitors as 
the last line of therapy. Subjects must have received ibrutinib for at least 6 months prior to 
screening. Ibrutinib administration will continue up to 30 hours prior to leukapheresis. In 
case of treatment interruption with ibrutinib, the principal investigator (PI) should reach out 
to the medical monitor to discuss. A 3+3 study design will be used to evaluate two doses of 
KTE-X19.
Cohort 4A: Up to 6 subjects will be enrolled and dosed at 1x106 anti-CD19 CAR T 
cells/kg. Decision to enroll in Cohort 4B will be based on SRT review of Cohort 4A.
Cohort 4B: Up to 6 subjects will be enrolled and dosed at 2x106 anti-CD19 CAR T 
cells/kg.


KTE-X19 
Kite Pha1ma, Inc. 
KTE-C19-108 (ZUMA-8) Statistical Analysis Plan 
Once a safe dose is established in Coho1t 4, additional subjects will be enrolled and dosed for a 
total of up to 12 subjects at the safe dose level. Up to 15 subjects in Coho1t 4 who are evaluable 
for dose-limiting toxicities (DLTs) will be assessed to evaluate the safety of KTE-X19. A safety 
review team (SRT) that is internal to the study sponsor, and in collaboration with at least 1 study 
investigator, will review safety data and make recommendations regarding further enrollment 
based on the incidence of DLTs and overall safety profile of KTE-X19. 
Each subject will proceed through the following study periods, as shown in the study schema 
(Figure 1): 
• 
Screening 
• 
Enrollment/Leukapheresis 
I 
• 
Lymphodepleting/Conditioning chemotherapy 
• 
Investigational product (IP) treatment 
• 
Post-treatment assessment 
• 
Long-te1m follow-up 
Fmther details on study procedures may be found in the study protocol. 
Figure 1. 
-~ 
1 
c.. 
"' 
-'< 
Study Schema for Study KTE-C19-108 
Condilioning ChNnot h('nlpV' 
(U:w -5 10 -3) 
In, estig:11 ion al ·r reatmen l 
K'TE-Xl9 -, rc:1tmen1 t'eciod 
(Q.u_fil 
Subjec.1 is hospituli.a--d prior to 
tr(":l.lmC-nl with K1'E-Xt9 and 
remarns ho:-pnah,cd ro, 
ob~cr,ation lbr a minimum or 
:::, 
<I) 
...l 
1-lu<larabin<· 30 mg/111'/da) 
Cycfophosphauudc-
500mg,'m2iday 
). J days 
_.... 
7 days arlc1 lr'C'.atmtnl 
-
E 
CONFIDENTIAL 
(l)ay-5 lO l)ay-3: 
Oa} -2anJ L>ay-1 an:~~• 
<lay,) 
Page9 
Kl C-XI 9 il the- de-finl"d dost-
(ltr 1ht spc.._~1fie Cohort 
21 Janua1y 2021 


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KTE-C19-108 (ZUMA-8) Statistical Analysis Plan
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3.2.
Hypothesis
No formal hypothesis testing is planned.
3.3.
Sample Size Consideration
For Cohort 1 and Cohort 2, the study will enroll and dose up to 9 subjects who are DLT 
evaluable in each cohort. The anticipated total enrollment for Cohort 3 and Cohort 4 is up to 
approximately 18 subjects.
Cohort 3 will enroll and dose 3 subjects in an exploratory cohort. No additional subjects will be 
enrolled or dose levels evaluated.
For Cohort 4, the SRT will review safety and PK data after 3 to 6 subjects in the DLT-evaluable 
set at each dose level have had the opportunity to be followed for 28 days after the KTE-X19 
infusion. If the lymphodepleting regimen and one or more KTE-X19 doses evaluated in the study 
are determined to be safe based on the incidence of DLT and to enable sufficient cell expansion, 
up to approximately total of 12 subjects may be enrolled in the dose cohort to further evaluate 
safety. The maximum number of subjects, including those enrolled and dosed in Cohort 4 will be 
approximately 15 subjects. 
3.4.
Statistical Assumptions
The independence of subject responses will be assumed.


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4.
THE INDEPENDENCE OF SUBJECT RESPONSES WILL BE 
ASSUMED. STUDY ENDPOINTS AND COVARIATES
4.1.
Endpoints
4.1.1.
Primary

Incidence of Dose Limiting Toxicities (DLTs) in subjects treated with KTE-X19. 
4.1.2.
Secondary

Incidence of adverse events (AEs) 

Levels of anti-CD19 CAR T-cells in blood

ORR (CR/CRi/PR) as defined by IWCLL 2018 criteria for selected safe dose cohort
 
 
4.2.
Covariates
Covariate levels that are sparse may be collapsed for purposes of statistical modeling.
CCI-
I 
I 
I 
I 
I 
I 
I 
I 
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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)

Age (in years) at baseline (< 65, ≥ 65)

Sex (male, female)

Region: US, EU, Australia

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)

Rai Disease stage (0, I-II, III-IV) 

Binet classification at time of diagnosis (A, B, C)

Number of prior chemotherapy regimens (2, 3, >3)

17p deletion (Y, N)

11q deletion (Y, N)

13q deletion (Y, N)

Trisomy 12 (Y, N)

Complex Karyotype (Y, N)

High risk feature (any of 17p deletion, 11q deletion, 13q deletion, trisomy 12, complex 
karyotype)

Beta 2 microglobulin (≤ 3.5mg/L, >3.5mg/L)

Baseline MRD (Positive, Negative)


KTE-X19 
Kite Pha1ma, Inc. 
KTE-C19-108 (ZUMA-8) Statistical Analysis Plan 
5_ 
DEFINITIONS 
5.1. 
General 
Study enrollment: Study enrollment occurs when a subject commences leukapheresis. 
Study day 0: Study day O is defined as the day the subject received the first KTE-X19 infusion. 
The day prior to study day O will be study day -1. Any days after enrollment and prior to study 
day -1 will be sequential and negative integer-valued. 
Baseline: The baseline value is defined as the last non-missing value taken prior to conditioning 
chemotherapy. For subjects without conditioning chemotherapy date, the baseline value is taken 
as the last non-missing value on the study. 
On-study: Time from enrollment to the last date of contact or death 
Actual follow-up time: Actual follow-up time among all subjects treated with KTE-X19 is 
calculated as the time from the first dose of KTE-X19 to the date of death, last date known 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 KTE-X19 
infusion to the data cutoff date for the analysis. 
5.2. 
Safety 
Primary Safety Analysis Period: The 
the first KTE-X19 infusion, 
Treatment-emergent adverse event 
EAE : An adverse event with onset on or after the 
. 
. 
. 
Deaths: All deaths that occur from the enrollment/leukapheresis up through the end of study 
will be summarized. Deaths that occur from the time of KTE-X19 infusion will also be 
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AEs of special interest:  Adverse events of special interest for KTE-X19 treatment include 
important identified risks (Cytokine release syndrome [CRS], neurologic toxicities, cytopenias, 
infections, and hypogammaglobulinemia) and important potential risks (including but may not 
limit to immunogenicity, new malignancies, Replication-competent retrovirus [RCR], graft 
versus host disease [GVHD], and tumor lysis syndrome [TLS]). 
CRS will be identified via a case report form (CRF) specifically designed to collect CRS as a 
syndrome. Specific symptoms of the CRS are collected on the AE log form and are linked to the 
CRS syndrome. CRS syndrome severity is graded according to a modification of the grading 
system proposed by Lee and colleagues {Lee 2014}.  In the modified grading scale, neurologic 
AEs are not reported as part of the CRS syndrome; rather, they are reported on the AE log form 
separately based on specific symptoms per Common Terminology Criteria for Adverse Events 
(CTCAE). 
Neurologic toxicity (Neurotoxicity) AEs will be identified by 2 search strategies:

Method 1: A Medical Dictionary for Regulatory Activities (MedDRA) search term list 
(MST) that was developed at Kite based on a modification of the search strategy described 
by Topp and colleagues {Topp 2015}.

Method 2: MedDRA System Organ Classes (SOCs) of psychiatric disorders and nervous 
system disorders, excluding the following 2 High-Level Group Terms (HLGTs): sleep 
disorders and disturbances and sleep disturbances (incl subtypes). MedDRA preferred terms 
may be added or removed based on FDA feedback.
Prolonged Cytopenias (Neutropenia or Thrombocytopenia or Anemia) will be identified as 
cytopenias present on or after Day 30 post KTE-X19 infusion. Prolonged cytopenias will be 
summarized separately by the 3 blood cell lineages.
Immunogenicity will be identified by testing for reactivity against FMC63, the parent murine 
antibody used for the development of the single-chain variable region fragment (scFv) of the 
anti-CD19 CAR construct. Positive samples will then be tested to confirm the presence of 
antibody to the extracellular portions of anti-CD19 CAR.
For other AEs of special interest, specific adverse events may be mapped to these categories 
using dictionary coded event term and SMQs or other search strategies. Specific definitions of 
these events and the coded terms to which they correspond will be provided in the Safety 
Monitoring Plan. 
Duration of an AE:  The duration of an AE of 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 resolution day of the last AE in the event class – the start day of the first AE in the 
event class + 1.  
Time to Onset of an AE: Time to onset of an AE of interest is defined as the interval from the 
date of the first infusion of KTE-X19 through the earliest onset date of the AEs in the event 
class, i.e., the start date of the first AE in the event class – the date of the first infusion of 
KTE-X19 + 1.


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5.3.
Efficacy
ORR:  ORR is the proportion of subjects with either a CR, CRi or PR while on study as defined 
by IWCLL 2018 criteria.  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 
 with KTE-X19).  Responses are defined per 
investigator review. 
Overall complete response rate (CR/CRi):  The overall complete response includes both 
complete response (CR) and complete response with incomplete hematopoietic recovery (CRi) 
per investigator review prior to the subsequent anticancer therapy and allogeneic SCT.
Minimum Residual Disease (MRD) Negative Rate:  The incidence of a minimal residual 
disease response (MRD-).  MRD- is defined as MRD < 10-4 per the standard assessment 
conducted in a central lab, ie one CLL cell per 10,000 leukocytes. MRD negative rate will be 
estimated for all dosed subjects, and for subjects with CR/CRi. 
DOR:  DOR is defined only for subjects who experience an objective response (CR/CRi/PR) and 
is the time from the first objective response to disease progression (PD) per IWCLL 2018 or 
death. 
 Subjects not meeting the 
criteria for PD or death by the analysis data cutoff date will be censored at their last evaluable 
disease assessment date before data cutoff.  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 new anti-cancer therapy including SCT 
 
will be censored at the last evaluable disease assessment date prior to the 
subsequent therapy. Additional details on the derivation of DOR are provided in Appendix 3. 
PFS:  PFS is defined as the time from the KTE-X19 infusion date to the date of disease 
progression or death from any cause. 
 
 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 before data cutoff.  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 new anti-cancer therapies including 
SCT while in response will be censored at the last evaluable disease assessment date prior to the 
subsequent therapy. Additional details on the derivation of PFS are provided in Appendix 3. 
OS:  OS is defined as the time from the KTE-X19 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.  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.  
CCI
CCI
CCI
CCI
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KTE-X19 
Kite Pha1ma, Inc. 
KTE-C19-108 (ZUMA-8) Statistical Analysis Plan 
6_ 
ANALYSIS SUBSETS 
6.1. 
DLT Evaluable Set 
All subjects treated with the target KTE-X19 dose and followed for at least 28 days, or received 
a dose of KTE-X19 lower than the target dose but experienced a DLT during the 28 day post 
infusion period, up to the time at which the maximum toxicity dose (MTD) is identified. 
Additional subjects enrolled and ti·eated subsequently for the pmpose of assessment of the 
overall safety in the same dose level or a lower dose level will not be considered as pali of the 
DLT evaluable set, and DLT will not be assessed for such subjects. 
6.2. 
All Treated Subjects 
All subjects ti·eated with any dose of KTE-X19 are included in the analysis set. 
6.3. 
Safety Analysis Set 
The safety analysis set is defined as all subjects ti·eated with any dose of KTE-X19. 
6.4. 
Full Analysis Set 
The full analysis set will consist of all enrolled subjects and may be used for the summaiy of 
subject disposition and subject listings of deaths. 
6.6. 
Subgroup Analysis Sets 
Subgroup analyses of selected efficacy and safety endpoints may be perfo1med for subgroups 
defined by the baseline covai·iates defined in Section 4.2. 
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7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES
7.1.
Safety Interim Analysis 
No formal interim analysis is planned for this phase 1 study. During the study, the SRT will 
review safety data after 3-9 DLT evaluable subjects at each dose level have had the opportunity 
to be followed for 28 days after the KTE-X19 infusion. The SRT will review the safety data and 
make recommendations on further study conduct and progression of the study. For details on the 
dose escalation/de-escalation plan based on the incidences of DLTs, please refer to the protocol. 
Please refer to SRT charter for details on safety data review.
7.2.
Assessment of Criteria to Pause Enrollment
Study enrollment will be paused following any grade 5 adverse event that occurs within 30 days 
of KTE-X19 infusion regardless of attributions.  
In the event that the enrollment is paused after the pausing criteria have been met, overall 
assessment of the benefit/risk ratio will be conducted. If the overall assessment of the benefit/risk 
ratio is favorable, the study can resume enrollment. Restart of the study may require prior 
approval if required by applicable regulatory requirements or mandated by in country Regulatory 
Agency. 
Enrollment will be paused if any of the following criteria is met:

Incidence of the following Grade 4 KTE-X19-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)
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. 


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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 Archiving 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 
partial missing 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.
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
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 Kite Standard Operating 
Procedures (SOPs). 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 timing of the EOP1 analyses will be based on subject accrual and safety or disease 
assessment milestones. The final analysis will occur when all subjects have completed the study.
All the analyses will be descriptive.
9.2.
Subject Accountability
The number of subjects enrolled/leukapheresed, treated with bridging therapy, treated with 
conditioning chemotherapy, treated with KTE-X19, and retreated with KTE-X19 (if applicable) 
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 KTE-X19 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 will be 
tabulated.
9.5.
Efficacy Analyses
The primary efficacy analyses will be conducted on the all treated subjects for the selected safe 
dose cohort. The investigators will assess the disease response based on the IWCLL 2018 
criteria. The investigators will provide the determination of disease status (CR, CRi, PR, SD, PD, 
not evaluable [NE]) at each time point. These assessments will be used to derive the best overall 
response (BOR), ORR, CR/CRi rate, MRD- rate, MRD- rate among CR/CRi subjects, DOR, and 
PFS. These efficacy analyses will also be performed only for the selected safe dose cohort.


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In the event any subject undergoes an SCT or any additional anti-cancer therapy while on study, 
the subject's best response will be derived only based on disease responses assessed prior to SCT 
or initiation of new therapy, whichever is earlier. (See details in Appendix 3). 
When the estimates are not generated due to small sample size, only descriptive statistics (mean, 
median, standard deviation, minimum and maximum, or percentages), as well as data listings by 
subject and visit, for each efficacy endpoint will be provided. 
9.5.1. 
9.5.1.1. 
ORR 
Analyses of ORR and Overall Complete Response Rate per Investigator 
Assessment 
The subject incidence of objective response rate (CR/CRi/PR) will be calculated. 95% 
confidence intervals will be provided about the ORR, calculated with the Clopper-Pearson (an 
exact interval). 
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9.6. 
Safety Analyses 
Safety analyses will be conducted on the safety analysis set. The primaiy analysis of safety data 
will sUII1Inai·ize TEAEs death and laborato1 values with onset on or after the KTE-X19 
AEs will be coded with the MedDRA at the time of each analysis. The version of the MedDRA 
may vaiy over time as the cunent version in use is updated. The severity of AEs will be graded 
using the National Cancer Institute CTCAE version 5.0. 
CRS will be graded using a revised CRS grading scale developed by Lee et al {Lee 2014}. 
Individual symptoms associated with CRS will be graded per CTCAE version 5.0. 
Fatal AEs that ai·e attributed to disease progression may be included in the death summa1y with a 
primaiy death reason of "chronic lymphocytic leukemia" regai·dless of the coded prefened te1m. 
Subjects emolled, but not dosed with KTE-X19, will be followed for AEs for 30 days after the 
last study-specific procedure, or until initiation of a new anti-cancer therapy, whichever occurs 
first. AEs repo1ied in these subjects will be ai·chived in the study database and available in 
SDTM and ADaM datasets, but will not be tabulated in AE summaries. 
Safety sUII1Inaries will be presented by coho1is. 
9.6.1. 
AEs 
The subject incidence of the following TEAEs will be tabulated: 
• 
Summa1y of AEs (any, worst severity, serious, treatment-related) 
• 
All AEs 
• 
All SAEs 
• 
All KTE-X19-related AEs 
• 
All KTE-X19-related SAEs 
• 
All Grade 3 or higher AEs 
• 
All Grade 3 or higher KTE-X19-related AEs 
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
Fatal AEs

AEs of special interest, including important identified risks and important potential risks 
The subject incidence summary of deaths and a subject listing of deaths will be provided. The 
primary reasons of death will also be summarized.
Subgroup analyses of AEs may be generated for selected covariates from the list in Section 4.2.1.  
The time to onset 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 the duration of neurologic events will be summarized. 
Cytopenias will be summarized by categories of neutropenia, anemia, and thrombocytopenia; 
cytopenias present on or after 30 days from KTE-X19 infusion will also be summarized.
Infections will be summarized by categories (bacterial infections, viral infections, opportunistic 
infections, and other infections).
New malignancies are based on search criteria of SOC Neoplasms benign, malignant, and 
unspecified (including cysts and polyps), excluding benign neoplasms and those events related to 
the primary malignancy. New non-melanoma skin cancers are not included in the summary. New 
malignancies will be listed.
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 5.0. 
The incidence of post-infusion worst-grade lab toxicities for all analytes will be summarized. 
Additional summaries for the shift from before infusion to the worst toxicity grade after KTE-
X19 infusion may also be generated. 
9.6.4.
Anti-KTE-X19 Antibodies
The subject incidence of any anti-KTE-X19 antibodies will be tabulated.  For subjects testing 
positive for antibodies, the persistence of the antibody over time will be listed. 
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 listed.


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9.6.6. 
Exposure to Study Treatment 
Summa1y 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 ofKTE-X19 
• 
Total CART cells of the KTE-X19 infusion 
• 
Total T cells of the KTE-X19 infusion 
• 
Transduction ratio 
9.6.7. 
Exposure to Concomitant Medications and Procedures 
The subject incidence of concomitant medications will be summarized by medication catego1y 
and WHO Dmg coded te1m, according to the version in use at analysis. The subject incidence of 
procedures will be tabulated. The indication of concomitant medications of interest for systemic 
steroids, tocilizumab, vasopressors, nonsteroidal immunosuppressants other than tocilizumab, 
and IV immunoglobulins defined by Kite, may be summarized. 
9.7. 
Product Characteristics 
A subject listing of product characteristics will be provided. Please refer to the Translational 
SAP for details. 
9.10. 
Subsequent Anti-Cancer Therapy 
The incidence of subsequent anti-cancer therapy (by WHO Dmg coded te1m) will be 
summarized. 
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9.11.
Duration Metrics 
Summary statistics will be provided for the following durations:

Days from leukapheresis to commencement of conditioning chemotherapy

Days from leukapheresis to KTE-X19 product release

Days from leukapheresis to delivery of KTE-X19 at study site

Days from leukapheresis to administration of KTE-X19

Days from conditioning chemotherapy to administration of KTE-X19

Duration of hospitalization for the KTE-X19 infusion


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10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES
None.


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11.
REFERENCES
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. Guidelines 
for diagnosis, indications for treatment, response assessment and supportive 
management of chronic lymphocytic leukemia. Blood 2018.
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.
APPENDICES
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or Missing Dates
Appendix 2.
IWCLL 2018 Response Criteria and Disease Response Assessment
Appendix 3.
Derivation of Time to Event Endpoints and Last Date Known to Be Alive
Appendix 4.
Binet and Rai Staging Systems for the Classification of CLL


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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
< 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.
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.
IWCLL 2018 Response Criteria and Disease Response Assessment
The determination of CLL response and progression will be based on standardized International Workshop on CLL (IWCLL) 2018 
criteria.
Table 2.
IWCLL 2018 Response Criteria
Parameter
CR
PR
PD
Group A (indicating tumor load)
Lymphadenopathy1
none ≥ 1.5 cm
decrease ≥ 50%
increase by ≥ 50% or new lymph 
nodes ≥ 1.5 cm
Hepatomegaly
none
decrease ≥ 50%
Increase by ≥ 50 %
Splenomegaly
none
decrease ≥ 50%
Increase by ≥ 50 %
Blood lymphocytes
< 4000/µL
decrease of ≥ 50% from baseline
Increase by ≥ 50% over baseline2 to 
≥ 5000/µL
Group B (indicating function of the hematopoietic system)
Platelet count
≥ 100,000/µL
≥ 100,000/µL or increase by ≥ 50% 
from baseline
Decrease by ≥ 50% from baseline 
due to CLL
Hemoglobin
≥ 11 g/dL
≥ 11 g/dL or increase by ≥ 50% from 
baseline
Decrease by ≥ 2 g/dL
Bone Marrow
Normocellular for age, no increase in 
CLL lymphocytes, no clonal 
B-lymphoid nodules3
CLL cells or clonal B-lymphoid 
nodules present
Increase in CLL cells by ≥50% on 
successive biopsies
1
Assessed as sum of the products of up to 6 lymph nodes
2
Subjects with treatment-related lymphocytosis should not be rated PD and remain on study treatment if other criteria for progressive disease are absent.
3
In case of B-lymphoid nodules assessment is recommended to clarify if the population is clonal—if not, subjects can be assessed as CR/CRi if all other criteria are fulfilled.


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Table 3.
Disease Response Assessment
Overall Disease 
Response
IWCLL Criteria 2018 
Additional Criteria
CR
All criteria for CR in Group A and B
No disease related symptoms should be present, neutrophil count 
≥ 1500/µL
CRi
All criteria for CR are met except with platelet count <100,000/µl, 
hemoglobin < 11 g/dL or neutrophil count < 1500/µL
 
PR
At least 1 criterion from Group A and 1 from Group B must be 
fulfilled.
If only one criterion is abnormal at baseline from Group A or B, 
only that criterion must improve.
SD
Failure to achieve a PR and absence of PD
 
PD
Presence of at least 1 of the criteria from Group A or Group B
Constitutional symptoms alone do not define PD. A bone marrow 
biopsy should be performed to confirm progression if blood count 
changes are the only evidence of progression.


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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), progression-free survival 
(PFS), and overall survival (OS) is provided below.
1) DOR
Table 4.
Analysis of DOR for Treated Subjects with Objective Response
Earliest Scenario since First Objective 
Response among PD, Death, New Therapy,  
Study W/D and Lost to Follow Up
Event/Censored
Date of Event/Censoring
Disease progression 
Event
First progression date 
Death 
Event
Death date 
New anti-cancer therapy (including SCT 
 
)
Censored
Last evaluable disease assessment date 
prior to the first new therapy (including 
SCT 
)
Withdrawal of consent or lost to follow-up
Censored
Last evaluable disease assessment date 
prior to data cutoff date
Remain in response by data cutoff
Censored
Last evaluable disease assessment date 
prior to data cutoff date
Abbreviations:  DOR, duration of response; SCT, stem cell transplant. 
Note: Time to event = Event / Censoring date - First response date + 1.
2) PFS
PFS is defined as the time from the KTE-X19 infusion date to the date of disease progression or 
death from any cause.  
 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 response 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. 
Table 5.
Analysis of PFS for Treated Subjects 
Earliest Scenario since Infusion among PD, 
Death, New Therapy, Study W/D and Lost to 
Follow Up
Event/Censored
Date of Event/Censoring
Disease progression 
Event
First progression date 
Death 
Event
Death date
New anti-cancer therapy (including SCT 
 
)
Censored
Last evaluable disease assessment date 
prior to the first new therapy (including 
SCT 
)
Withdrawal of consent or lost to follow-up
Censored
Last evaluable disease assessment date 
prior to data cutoff date
CCI
CCI
CCI
CCI
CCI
CCI
CCI
-
-


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Earliest Scenario since Infusion among PD, 
Death, New Therapy, Study W/D and Lost to 
Follow Up
Event/Censored
Date of Event/Censoring
Progression-free and alive by data cutoff
Censored
Last evaluable disease assessment date 
prior to data cutoff date
Disease response yet to be assessed
Censored
KTE-X19 infusion date
Abbreviations:  PFS, progression-free survival; SCT, stem cell transplant.
Note: Time to event = Event / Censoring date - First infusion date + 1
3) OS
OS is defined as the time from the KTE-X19 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.
Table 6.
Analysis of OS for Treated Subjects
Circumstance
Event/Censored
Date of Event/Censoring
Death (non-missing death date ≤ cutoff date)
Event
Death date
Alive (either death date or last known alive date 
> cutoff date)
Censored
Data cutoff date
Alive (death date is missing and last known 
alive date ≤ cutoff date)*
Censored
Last known alive date
Abbreviation:  OS, overall survival.
Note: Time to event = Event / Censoring date - First infusion date + 1
*
If the subject withdrew full consent or was lost to follow up prior to data cutoff date, then such information will be indicated 
in the summaries of OS.
4) 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

KTE-X19 infusion dates

Computerized tomography (CT) scan dates

Positron emission tomography (PET) scan dates


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
Index lesion assessment

Non-index lesion assessment

New lesion assessment

Other tumor assessment dates (Bone marrow, liver and spleen assessments)

Disease response assessment

Long-term follow-up subject status date where status = alive or death

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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Appendix 4.
Binet and Rai Staging Systems for the Classification of CLL
Binet
Stage
Lymph Node Areas
Hemoglobin
< 10 g/dL
Platelet
< 100 × 109/L
A
< 3
No
No
B
≥ 3
No
No
C
±
Either present
Rai
Stage
Lymphocytosis
Lymph Node 
Enlargement
Spleen/Liver 
Enlargement
Hemoglobin 
< 11 g/dL
Platelet
< 100 × 109/L
0
Yes
No
No
No
No
I
Yes
Yes
No
No
No
II
Yes
±
Yes
No
No
III
Yes
±
±
Yes
No
IV
Yes
±
±
±
Yes