Clinical trial NCT02614066
Conditions: Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Sponsor: Kite, A Gilead Company
Start date: 2016-03-07; Completion date: 2023-11-03
Enrollment: 125 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objectives of this study are to determine the safety and efficacy of brexucabtagene autoleucel (KTE-X19) in adult participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL).

Detailed description:
Bridging therapy could be administered at the discretion of the investigator and is recommended for participants with high disease burden at baseline (M3 marrow \[\> 25% leukemic blasts\] or ≥ 1,000 blasts/mm\^3 in the peripheral circulation) to control participant's disease prior to conditioning chemotherapy. Bridging therapy includes:

Attenuated VAD: Vincristine non-liposomal (1-2 mg IV weekly) or liposomal (2.25 mg/m\^2 IV weekly), and dexamethasone 20-40 mg IV or oral administration (PO) daily x 3-4 days per week. Optional doxorubicin 50 mg/m\^2 IV x 1 (first week only).

Mercaptopurine (6-MP): 50-75 mg/m\^2/day by mouth (administer at bedtime on an empty stomach to improve absorption).

Hydroxyurea: Doses titrated between 15-50 mg/kg/day (rounded to the nearest 500 mg capsule and given as a single daily oral dose on a continuous basis).

DOMP: Dexamethasone 6 mg/m\^2/day PO (or IV) divided twice daily (BID) Days 1-5, vincristine 1.5 mg/m\^2 (maximum dose 2 mg) IV on Day 1, methotrexate 20 mg/m\^2 PO weekly, 6-MP 50- 75mg/m\^2/day PO daily.

Attenuated FLAG/FLAG-IDA: fludarabine 30 mg/m\^2 IV days 1-2, cytarabine 2 g/m\^2 IV days 1-2, G-CSF 5 μg/kg subcutaneously (SC) or IV starts on Day 3 and can continue until day before the start of conditioning chemotherapy. With or without idarubicin 6 mg/m\^2 IV Days 1-2.

Mini-hyper CVAD (courses A and/or B):

* Course A: Cyclophosphamide 150 mg/m\^2 every 12 hours x 3 days, dexamethasone 20 mg/d IV or PO daily Days 1-4 and 11-14, vincristine 2 mg IV x 1
* Course B: Methotrexate 250 mg/m\^2 IV over 24 hours on Day 1,cytarabine 0.5 g/m\^2 IV every 12 hours x 4 doses on Days 2 and 3.

After completion of the Month 24 visit, 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, KT-US-982-5968

Arms: arm 1: Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 intravenously \[IV\] over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel (KTE-X19) chimeric antigen receptor (CAR) transduced autologous T cells at a target dose of 2 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered. arm 2: Participants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 1 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered. arm 3: Participants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 0.5 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 0.5 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered. arm 4: Participants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m\^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m\^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 1 x 10\^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing \> 100 kg, a maximum flat dose of 1 x 10\^8 anti-CD19 CAR T cells/kg of body weight will be administered.
Interventions: intervention 1: brexucabtagene autoleucel intervention 2: Cyclophosphamide intervention 3: Fludarabine
Intervention descriptions: intervention 1: A single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered intravenously. intervention 2: Administered intravenously. intervention 3: Administered intravenously.

Protocol documents:
Prot_002.pdf: 
 
CLINICAL STUDY PROTOCOL
Protocol Title:
A Phase 1/2 Multi-Center Study Evaluating the Safety and 
Efficacy of KTE-X19 in Adult Subjects with Relapsed/Refractory 
B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)
Protocol Number:
KTE-C19-103 (ZUMA-3)
Kite Investigational 
Product: 
USAN:
KTE-X19 
Brexucabtagene Autoleucel
IND Number:
EudraCT Number:
ClinicalTrials.gov 
Identifier:
016675
2015-005009-35
NCT02614066
Clinical Study Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Key Sponsor Contacts:
The medical monitor name and contact information is included on 
the Study Contact Lists distributed by the CRO.
Protocol Version/Date:
Original: 
07 May 2015
Amendment 7: 
14 December 2021
Confidentiality Statement
This document contains confidential information of Kite Pharma Inc., a wholly owned 
subsidiary of Gilead Sciences, Inc.  This document must not be disclosed to anyone other than 
study site research staff, collaborators and members of the Institutional Review 
Board/Independent Ethics Committee, a scientific review board, or an equivalent. The 
information in this document cannot be used for any purpose other than the conduct of the 
clinical investigation without the prior written consent of Kite Pharma, Inc.


KTE-X19 
Kite Pharma, Inc. 
Protocol KTE-C19-103 
Amendment 7 
CONFIDENTIAL 
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SPONSOR AND INVESTIGATOR SIGNATURE PAGE 
KITE PHARMA, INC. 
2400 BROADWAY 
SANTA MONICA, CA 90404 
STUDY ACKNOWLEDGEMENT 
A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-X19 in Adult 
Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) 
(ZUMA-3) 
Amendment 7.0, 14 December 2021 
This protocol has been approved by Kite Pharma, Inc. The following signature documents this 
approval. 
Kite Medical Monitor Name (Printed) 
Sig
Date 
INVESTIGATOR STATEMENT 
I have read the attached protocol, including all appendices, and I agree that it contains all 
necessary details for me and my staff to conduct this study as described. I will conduct this study 
as outlined herein and will make a reasonable effort to complete this study within the time 
designated.  
I agree to comply with the International Council for Harmonisation of Technical Requirements 
for Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline on Good Clinical 
Practice and applicable national or regional regulations and guidelines. I will provide all study 
personnel under my supervision copies of the protocol and access to all information provided by 
Kite Pharma, Inc. I will discuss this material with them to ensure that they are fully informed 
about the investigational product and study. 
I agree and will ensure that financial disclosure statements will be completed by: 
x
Me (including, if applicable, my spouse, legal partner and dependent children)
x
Sub-Investigators (including, if applicable their spouse, legal partner and dependent children)
at the start of the study and for up to 1 year after the study is completed.
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the clinical investigation without prior written consent 
from Kite Pharma Inc. 
Principal Investigator Name (Printed) 
Signature 
Date 
Site Number 
PPD
PPD
PPD


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STUDY GLOSSARY
AE
adverse event
ALL
acute lymphoblastic leukemia
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
CAR
chimeric antigen receptor 
CAR+
chimeric antigen receptor positive
CBC
complete blood count
CLL
chronic lymphocytic leukemia
CNS
central nervous system
CPF
cell processing facility
CR
complete remission
CRh
complete remission response with partial hematologic recovery
CRi
complete remission response with incomplete hematologic recovery
CRF
case report form
CRS
cytokine release syndrome
CSF
cerebrospinal fluid
CTCAE
common terminology criteria for adverse events
ddPCR
droplet digital polymerase chain reaction
DLBCL
diffuse large B-cell lymphoma
DLT
dose-limiting toxicity
DOR
duration of remission
DSMB
data safety monitoring board
DVT
deep vein thrombosis
eACT™
engineered autologous cell therapy 
ECHO
echocardiogram
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EEG
electroencephalogram
End of Study for individual 
subject
Defined as when the last day that protocol specified assessments are conducted 
for an individual subject
End of Study (primary 
completion)
Defined as when the last subject is assessed or received an intervention for the 
purposes of final collection of data for the primary endpoint at Week 8 
End of Study (end of trial)
Defined as when the last subject is assessed or received an intervention for 
evaluation in the study, including survival assessments 
High Burden Disease
M3 marrow (>25% leukemic blasts) or ≥ 1000 blasts/mm3 in the peripheral 
circulation
HLH
Hemophagocytic lymphohistiocytosis
ICF
informed consent form
IHC
immunohistochemistry


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IL
interleukin
IL-2R
interleukin-2 receptor
IP
investigational product
IPM
Investigational product manual
IRB/IEC
institutional review board/independent ethics committee
KTE-X19
autologous T cells transduced with retroviral vector containing anti-CD19 
CD28/CD3-zeta chimeric antigen receptor
LMWH
low-molecular weight heparin
LTFU
long term follow-up
LVEF
left ventricular ejection fraction
mITT
modified intend to treat
MTD
maximum tolerated dose
MRD
minimal residual disease
MTD
maximum tolerated dose
NCI
National Cancer Institute
NHL
non-Hodgkin lymphoma
OS
overall survival
PBMC
peripheral blood mononuclear cells
PET
positron emission tomography
Ph+
Philadelphia chromosome positive
PMBCL
primary mediastinal B-cell lymphoma 
PD
progressive disease
PR
partial response
qPCR
quantitative polymerase chain reaction
RCR 
replication competent retrovirus
RFS
relapse-free survival
r/r
relapsed/refractory
SAE
serious adverse event
scFv
single chain variable fragment
SMZL
splenic marginal zone lymphoma
SOA
schedule of assessments
SOC
standard of care
SCT
stem cell transplant
Study day 0
Defined as the first day that KTE-X19 is administered to the subject
TEAEs
treatment-emergent adverse events 
TKI
tyrosine kinase inhibitor
TLS
tumor lysis syndrome
TNF
tumor necrosis factor
ULN
upper limit normal
WBC
white blood cell


KTE-X19
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PROTOCOL SYNOPSIS
Title:
A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of 
KTE-X19 in Adult Subjects with Relapsed/Refractory B-precursor 
Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)
Indication:
The indication is for the treatment of adult subjects with B-precursor r/r 
ALL.
Study Design:
ZUMA-3 is a Phase 1/2, multicenter, open-label study evaluating the 
safety and efficacy of KTE-X19 in adult subjects with relapsed or 
refractory B-precursor ALL.  In this study, relapsed or refractory is 
defined as one of the following: primary refractory; first relapse 
following a remission lasting ≤ 12 months; relapsed or refractory after 
second-line or higher therapy;  relapsed or refractory after allogenic 
SCT (provided the transplant occurred ≥ 100 days prior to enrollment 
and that no immunosuppressive medications were taken ≤ 4 weeks 
prior to enrollment). 
Phase 1 Study
During Phase 1, approximately 3-12 subjects with high burden [M3 
marrow (>25% leukemic blasts) or ≥1000 blasts/mm3 in the peripheral 
circulation] r/r ALL disease who are evaluable for DLT 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 in Phase 1 or 
proceeding to Phase 2 based on the incidence of DLTs and overall 
safety profile of KTE-X19.  Up to approximately 40 additional subjects 
with high or low burden disease may be enrolled to further assess 
safety (see Figure 1, Section 3.1 and Section 9.6).  
Phase 2 Study
During Phase 2, approximately 50 subjects in the modified-intention to 
treat (mITT) set will be assessed to evaluate the efficacy and safety of 
KTE-X19.   
An independent Data Safety Monitoring Board (DSMB) will review 
safety data through one interim analysis during the Phase 2 portion of 
the study.  In this interim analysis, the DSMB will review safety data 
after 20 Phase 2 subjects have been treated with KTE-X19 and had the 
opportunity to be followed for 30 days after the KTE-X19 infusion.  
Each subject will provide consent and be evaluated for study 
participation.  Once deemed eligible and enrolled into the study, each 
subject will follow the same study treatment schedule and procedural 
requirements, independent of the phase of the study, and proceed 
through the following study periods:


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
Screening period 

Enrollment/Leukapheresis period

Bridging chemotherapy and cerebrospinal fluid (CSF) prophylaxis 
period

Conditioning chemotherapy period

Investigational Product (IP) treatment period

Post treatment assessment period

Long term follow-up period
For study requirements assigned to each study period, refer to the 
schedule of assessments and Section 7 for details.
Study Objectives:
Phase 1 Study
The primary objective of Phase 1 is to evaluate the safety of KTE-X19.  
Phase 2 Study
The primary objective of Phase 2 is to evaluate the efficacy of 
KTE-X19, as measured by the overall complete remission rate defined 
as complete remission (CR) and complete remission with incomplete 
hematologic recovery (CRi) in adult subjects with r/r ALL 
(Appendix 1).  Secondary objectives will include assessing the safety 
and tolerability of KTE-X19 and additional efficacy endpoints.
Hypothesis: 
This study is designed to differentiate between a treatment that has a 
true overall complete remission rate of 40% or less and a treatment 
with a true overall complete remission rate of 65% or more.  The 
hypothesis is that the overall complete remission rate to KTE-X19 is 
significantly greater than 40%.
Primary 
Endpoints:

Phase 1: Incidence of adverse events (AEs) defined as dose-
limiting toxicities (DLTs) in the DLT evaluable set

Phase 2:  Overall complete remission rate (CR + CRi) per 
independent review (Appendix 1)
Secondary 
Endpoints:

Overall complete remission rate (CR + CRi) per investigator 
assessment (Appendix 1)

Duration of Remission (DOR)

Minimal Residual Disease (MRD) negative rate

Allogeneic stem cell transplant (Allogeneic SCT) rate

Overall survival (OS)

Relapse-free Survival (RFS)


KTE-X19 
Protocol KTE-Cl9-103 
Sample Size 
Study Eligibility 
Treatment 
CONFIDENTIAL 
Kite Pha1ma, Inc. 
Amendment 7 
• 
Incidence of AEs and common tenninology criteria for adverse 
events (CTCAE) grade changes in safety laborato1y values 
• 
Incidence of anti-KTE-X19 antibodies 
• 
Changes over time in the EQ-5D score and VAS score (phase 2 
only) 
In total, up to approximately 100 subjects may be emolled and treated 
with KTE-X19 in the study in Phase 1 and 2 combined (see 
Sections 9.6 and 10.3). 
• 
Phase 1: Approximately 3-12 subjects evaluable for DLT and up to 
approximately 40 additional subjects 
• 
Phase 2: Approximately 50 subjects in the mITT set 
Please refer to Section 5 for a complete and detailed list of inclusion 
and exclusion criteria for both phases of the study. 
Bridging chemotherapy: 
• 
Bridging chemotherapy is recommended for all subjects 
particularly for those subjects with high disease burden at screening 
[M3 maITow (>25% leukemic blasts) or ~1000 blasts/mm3 in the 
peripheral circulation] 
• 
If prescribed, bridging chemotherapy must be administered after 
leukapheresis and completed at least 7 days or 5 half-lives, 
whichever is shorter, prior to initiating conditioning chemotherapy. 
• 
Allowed bridging chemotherapy regimens are listed in Section 6.3, 
Table 2. Doses listed are recommended and can be adjusted for 
age/comorbidities or per local or institutional guidelines. 
• 
Refer to Sections 6.3 and 7.11.4 for fmi her details. 
Page7 
14 December 2021 


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CSF Prophylaxis:

All subjects will receive CSF prophylaxis consisting of an 
intrathecal regimen according to institutional or national guidelines 
(eg, methotrexate 12 to 15 mg, cytosine arabinoside 40 mg, or 
dexamethasone 4 mg or equivalent steroid dose).  

CSF prophylaxis will be administered any time during screening 
(eg, at time of screening lumbar puncture) through 7 days prior to 
KTE-X19 infusion.  

Subjects who are enrolled with CNS-2 disease at baseline must 
receive CSF prophylaxis after leukapheresis and at least 7 days 
prior to KTE-X19 infusion, unless otherwise approved by the Kite 
Medical Monitor.   

Multiple doses of CSF prophylaxis can be given per investigator 
discretion in accordance with institutional guidelines, but at least 
7 days must pass between the last dose of CSF prophylaxis and 
KTE-X19 infusion.  

Additional CSF prophylaxis may be given post-KTE-X19 infusion 
per investigator discretion in accordance with institutional 
guidelines, but should be avoided for at least 8 weeks after 
KTE-X19 infusion if possible.  

Refer to Sections 6.4 and 7.11.5 for further details.
Conditioning Chemotherapy:

All subjects will receive conditioning chemotherapy consisting of 
fludarabine and cyclophosphamide.

Fludarabine will be given at a dose of 25 mg/m2/day intravenously 
(IV) over 30 minutes on Day-4, Day -3, and Day 2 prior to 
KTE-X19 infusion.

Cyclophosphamide will be given at a dose of 900 mg/m2/day IV 
over 60 minutes on Day -2 prior to KTE-X19 infusion. 

Refer to Sections 6.5 and 7.11.6 for further details. 
Investigational Product:

The day of KTE-X19 infusion is considered Day 0.

KTE-X19 infusion will be administered at a target dose of 2 x 106 
anti-CD19 CAR T cells/kg, 1 x 106 anti-CD19 CAR T cells/kg, or 
0.5 x 106 anti-CD19 CAR T cells/kg (see Figure 1, Section 3.1 and 
Section 9.6). 

All subjects will be hospitalized to receive KTE-X19 infusion 
followed by a minimum 7 day observation period unless otherwise 
required by country regulatory agencies (refer to Appendix 3 for 
details). 

Refer to Sections 6.6 and 7.11.7 for further details.


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Procedures
At specific time points as outlined in the schedule of assessments, 
subjects will undergo the following procedures: 

Collection of informed consent, general medical history including 
previous treatments for ALL, physical exam including height and 
weight, vital signs, ECOG performance status, and neurological 
assessments.

Lumbar punctures for collection of cerebral spinal fluid (CSF).

Bone marrow biopsies/aspirates. 

If applicable, imaging modality appropriate for the anatomical site 
and clinical scenario (eg, positron emission tomography [PET], 
magnetic resonance imaging [MRI] for central nervous system 
[CNS] lesion, ultrasound for testicular lesion, computed 
tomography [CT] for intra-abdominal or thoracic lesions), will be 
performed to assess extramedullary disease status. 

Blood will be drawn and assessed locally for complete blood count 
(CBC) with differential, chemistry panels, C-reactive protein, and 
CD3 count.  CD19 expression will be assessed locally in subjects 
with prior blinatumomab treatment by flow cytometry or 
immunohistochemistry (IHC) on blasts obtained from peripheral 
blood or bone marrow.

Women of child-bearing potential will undergo a urine or serum 
pregnancy test. 

Blood will be drawn and submitted to the central lab for: cytokines, 
lymphocyte subsets, anti-KTE-X19 antibodies, replication 
competent retrovirus (RCR) and anti-CD19 CAR T cell analysis. 

Subjects will also undergo a baseline electrocardiogram (ECG) and 
echocardiogram (ECHO)

Leukapheresis. 

Routinely throughout the conduct of the study, subjects will be 
asked to report concomitant medications and adverse events.  

Subjects in phase 2 will complete the EQ-5D questionnaire.
Safety Review 
Team and Data 
Safety Monitoring 
Board
During Phase 1, approximately 3-12 subjects with high burden [M3 
marrow (>25% leukemic blasts) or ≥1000 blasts/mm3 in the peripheral 
circulation] r/r ALL disease who are evaluable for DLT 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 in Phase 1 or 
proceeding to Phase 2 based on the incidence of DLTs and overall 


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safety profile of KTE-X19.  Up to approximately 40 additional subjects 
with high or low burden disease may be enrolled to further assess 
safety (see Figure 1, Section 3.1 and Section 9.6).  
During Phase 2, approximately 50 subjects in the modified-intention to 
treat (mITT) set will be assessed to evaluate the efficacy and safety of 
KTE-X19.   
An independent Data Safety Monitoring Board (DSMB) will review 
safety data through one interim analysis during the Phase 2 portion of 
the study.  In this interim analysis, the DSMB will review safety data 
after 20 Phase 2 subjects have been treated with KTE-X19 and had the 
opportunity to be followed for 30 days after the KTE-X19 infusion.  
Statistical 
Considerations
The primary endpoint for the Phase 2 study is the overall complete 
remission rate (CR and CRi) per independent review (Appendix 1).  
This endpoint will be based on a mITT population consisting of all 
Phase 2 subjects who receive KTE-X19 dose (see Section 10.5).  
This study uses a single-arm design to test for an improvement in 
overall complete remission rate.  For the test of efficacy this study has 
approximately 93% power to distinguish between an active therapy 
with a 65% true overall complete remission rate from a therapy with an 
overall complete remission rate of 40% or less with a 1-sided alpha 
level of 0.025.  
During Phase 1, the SRT will review safety data after 3 subjects in the 
DLT evaluable set (see Section 10.5) have had the opportunity to be 
followed for 28 days after the KTE-X19 infusion (see Section 9.6).  
During Phase 2, one interim and one primary analysis will be 
performed.  The interim analysis is for safety only and will be 
performed by the DSMB after 20 Phase 2 subjects have been treated 
with KTE-X19 and had the opportunity to be followed for 30 days after 
the KTE-X19 infusion.  Additional interim analyses for safety may be 
requested by the DSMB.  
The primary analysis will occur when the overall study enrollment is 
complete and the last treated subject in the mITT set has had the 
opportunity to complete the month 6 disease assessment.  
A secondary endpoint, MRD-negative rate, will be tested against an 
MRD-negative rate of 30% if the testing of the primary endpoint is 
significant.


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Study Schema
Conditioning Chemotherapy 
Period 
Fludarabine 25 mg/m2/day 
IV over 30 minutes on Day -
4, Day -3 and Day -2. 
Cyclophosphamide 900 
mg/m2/day IV over 60 
minutes on Day -2 only
Day -1: Rest
Investigational Product (IP) 
Treatment Period 
Subject is hospitalized prior 
to KTE-X19 infusion
KTE-X19 is infused 
intravenously on Day 0
Post Treatment Assessment Period 
Long Term Follow-up Period$
Enrollment / Leukapheresis
Screening
† CSF Prophylaxis (administered any time during screening through 7 days prior to KTE-X19 infusion):
All subjects will receive CSF prophylaxis consisting of an intrathecal regimen according to institutional or national guidelines must be administered.  CSF prophylaxis 
may be administered with the screening lumbar puncture.  See Section 6.4 for additional details.
* Bridging Chemotherapy (administered after leukapheresis and completed at least 7 days or 5 half-lives, whichever is shorter, prior to initiating 
conditioning chemotherapy)
Bridging chemotherapy is recommended for all subjects particularly those subjects with high disease burden at screening [M3 marrow (>25% leukemic blasts) or 
≥1000 blasts/mm3 in the peripheral circulation].  See Section 6.3 for details.
$   After completion of the Month 24 visit, 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, KT-US-982-5968. 
CSF Prophylaxis †
&
Bridging 
Chemotherapy* 
t 
t 
t 
t 
t 


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TABLE OF CONTENTS
SPONSOR AND INVESTIGATOR SIGNATURE PAGE............................................................................................2
STUDY GLOSSARY .....................................................................................................................................................3
PROTOCOL SYNOPSIS................................................................................................................................................5
TABLE OF CONTENTS..............................................................................................................................................12
LIST OF IN-TEXT TABLES .......................................................................................................................................14
LIST OF IN-TEXT FIGURES......................................................................................................................................14
1.
OBJECTIVES.......................................................................................................................................................15
2.
DISEASE BACKGROUND AND RATIONALE...............................................................................................16
2.1.
Overview of ALL and Epidemiology......................................................................................................16
2.2.
Diagnosis and Subtyping of ALL............................................................................................................16
2.3.
Philadelphia Positive vs. Negative ALL .................................................................................................16
2.4.
Treatment and Prognosis .........................................................................................................................16
2.4.1.
First-line Treatment...............................................................................................................17
2.4.2.
Second-line and Beyond Treatment ......................................................................................17
2.4.3.
Minimal Residual Disease (MRD) ........................................................................................19
2.5.
Study Rationale .......................................................................................................................................19
2.5.1.
CD19 and Expression............................................................................................................19
2.5.2.
Anti-CD19 CAR T-cell Product............................................................................................20
2.6.
Clinical Experience with Anti-CD19 CAR T Cells in Studies Conducted at the National 
Cancer Institute (NCI) .............................................................................................................................20
2.7.
KTE-C19-101 ZUMA-1 Experience.......................................................................................................20
2.8.
KTE-X19-103 ZUMA-3 Phase 1 Experience .........................................................................................21
3.
KTE-X19-103 STUDY DESIGN.........................................................................................................................22
3.1.
General Study Design..............................................................................................................................22
3.2.
Participating Sites....................................................................................................................................23
3.3.
Number of Subjects .................................................................................................................................23
3.4.
Replacement of Subjects .........................................................................................................................24
3.5.
Study Duration.........................................................................................................................................24
3.5.1.
Study Duration for Individual Subjects.................................................................................24
3.5.2.
Completion of Study..............................................................................................................24
3.5.3.
Long-term Follow-up Period.................................................................................................24
4.
SUBJECT SCREENING AND ENROLLMENT................................................................................................25
5.
SUBJECT ELIGIBILITY.....................................................................................................................................26
5.1.
Inclusion Criteria.....................................................................................................................................26
5.2.
Exclusion Criteria....................................................................................................................................27
6.
PROTOCOL TREATMENT................................................................................................................................30
6.1.
Treatment Terminology...........................................................................................................................30
6.2.
Leukapheresis (within approximately 5 days of eligibility confirmation) ..............................................30
6.3.
Bridging Chemotherapy ..........................................................................................................................30
6.4.
CSF Prophylaxis......................................................................................................................................31
6.5.
Conditioning Chemotherapy ...................................................................................................................32
6.5.1.
Fludarabine............................................................................................................................32
6.5.2.
Cyclophosphamide ................................................................................................................32
6.5.3.
Mesna ....................................................................................................................................32
6.5.4.
Rationale for Conditioning Chemotherapy Choice and Dose ...............................................33
6.6.
KTE-X19 .................................................................................................................................................33


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6.6.1.
Rationale for KTE-X19 Dose................................................................................................34
6.7.
Concomitant Therapy ..............................................................................................................................34
6.8.
Excluded Medications .............................................................................................................................35
6.9.
Subsequent Therapy ................................................................................................................................36
6.10.
Toxicity Management..............................................................................................................................37
7.
STUDY PROCEDURES......................................................................................................................................38
7.1.
Informed Consent ....................................................................................................................................38
7.2.
Demographic Data...................................................................................................................................38
7.3.
Medical and Treatment History...............................................................................................................38
7.4.
Physical Exam, Vital Signs, Performance Status, and European Quality of Life-5 Dimensions 
(EQ-5D)...................................................................................................................................................39
7.5.
Neurological Assessment ........................................................................................................................39
7.6.
Cardiac Function .....................................................................................................................................39
7.7.
Lumbar Puncture .....................................................................................................................................40
7.8.
Laboratory ...............................................................................................................................................40
7.9.
Disease Assessments ...............................................................................................................................42
7.9.1.
Bone Marrow Evaluation ......................................................................................................42
7.9.2.
Imaging Requirements (Only Applies to Subjects with Known Non-CNS 
Extramedullary Disease at Baseline).....................................................................................44
7.10.
Biomarkers ..............................................................................................................................................44
7.11.
Procedures by Study Period.....................................................................................................................46
7.11.1.
Screening ...............................................................................................................................46
7.11.2.
Rescreening ...........................................................................................................................48
7.11.3.
Enrollment/Leukapheresis.....................................................................................................48
7.11.4.
Bridging Chemotherapy Period.............................................................................................50
7.11.5.
CSF Prophylaxis Period ........................................................................................................50
7.11.6.
Conditioning Chemotherapy and KTE-X19 Infusion ...........................................................51
7.11.7.
Investigational Product Treatment Period.............................................................................54
7.11.8.
Post-treatment Assessment Period ........................................................................................58
7.11.9.
Long-term Follow-up Period.................................................................................................59
8.
SUBJECT WITHDRAWAL ................................................................................................................................67
8.1.
Reasons for Removal from Treatment ....................................................................................................67
8.2.
Reasons for Removal from Study............................................................................................................68
9.
SAFETY REPORTING........................................................................................................................................69
9.1.
Adverse Events........................................................................................................................................69
9.1.1.
Diagnosis Versus Signs and Symptoms ................................................................................69
9.1.2.
Abnormal Vital Sign Values .................................................................................................70
9.1.3.
Reporting Abnormal Laboratory Findings ............................................................................70
9.2.
Reporting of Adverse Events...................................................................................................................70
9.3.
Definition of Serious Adverse Events .....................................................................................................72
9.3.1.
Hospitalization and Prolonged Hospitalization.....................................................................72
9.4.
Reporting Deaths.....................................................................................................................................73
9.5.
Reporting of Serious Adverse Events......................................................................................................73
9.6.
Pregnancy and Lactation .........................................................................................................................74
9.7.
Safety Review Team and Dose-limiting Toxicity...................................................................................75
9.8.
Data Safety Monitoring Board ................................................................................................................77
9.9.
Criteria to Pause Enrollment ...................................................................................................................77
10.
STATISTICAL CONSIDERATIONS.................................................................................................................79
10.1.
Hypothesis ...............................................................................................................................................79
10.2.
Study Endpoints.......................................................................................................................................79
10.2.1.
Primary ..................................................................................................................................79
10.2.2.
Secondary ..............................................................................................................................79


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10.2.3.
10.2.4.
Covariates..............................................................................................................................81
10.3.
Sample Size Considerations ....................................................................................................................81
10.4.
Statistical Assumptions ...........................................................................................................................82
10.5.
Analysis Subsets......................................................................................................................................82
10.6.
Access to Individual Subject Treatment Assignments ............................................................................82
10.7.
Interim Analysis ......................................................................................................................................82
10.8.
Planned Method of Analysis ...................................................................................................................83
10.8.1.
Overall Complete Remission Rate ........................................................................................83
10.8.2.
Duration of Remission...........................................................................................................83
10.8.3.
MRD-negative rate ................................................................................................................83
10.8.4.
CR Rate, CRi Rate, and DOR to Treatment Among Subjects Retreated 
with KTE-X19 for Progressive Disease after Initial Remission ...........................................83
10.8.5.
Overall Survival.....................................................................................................................84
10.8.6.
Allogeneic Stem Cell Transplant Rate ..................................................................................84
10.8.7.
Safety.....................................................................................................................................84
10.8.8.
Long-term Data Analysis ......................................................................................................84
11.
REGULATORY OBLIGATIONS.......................................................................................................................85
11.1.
Independent Review Board /Independent Ethics Committee..................................................................85
11.2.
Subject Confidentiality............................................................................................................................85
11.3.
Investigator Signatory Obligations..........................................................................................................85
12.
PROTOCOL AMENDMENTS AND TERMINATION .....................................................................................86
13.
STUDY DOCUMENTATION AND ARCHIVE ................................................................................................87
14.
STUDY MONITORING AND DATA COLLECTION......................................................................................88
15.
PUBLICATION ...................................................................................................................................................89
16.
COMPENSATION...............................................................................................................................................90
17.
REFERENCES.....................................................................................................................................................91
18.
APPENDICES......................................................................................................................................................95
Appendix 1.
OVERALL DISEASE RESPONSE CLASSIFICATION.......................................................96
Appendix 2.
EXTRAMEDULLARY DISEASE RESPONSE ....................................................................97
Appendix 3.
SCHEDULE OF ASSESSMENTS FOR GERMAN SUBJECTS FOLLOWING 
KTE-X19 INFUSION..............................................................................................................98
LIST OF IN-TEXT TABLES
Table 1.
Complete Response (CR) Rate in Adult B-Precursor Acute Lymphoblastic 
Leukemia (B-ALL) in the Relapsed/Refractory Setting..........................................................18
Table 2.
Bridging Chemotherapy Regimens .........................................................................................31
Table 3.
Reporting Requirements for Concomitant Medications..........................................................35
Table 4.
Schedule of Assessments.........................................................................................................62
Table 5.
Reporting Requirements for Adverse Events ..........................................................................71
Table 6.
Reporting Requirements for Serious Adverse Events .............................................................74
LIST OF IN-TEXT FIGURES
Figure 1.
Phase 1 Dosing ........................................................................................................................23
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1.
OBJECTIVES
The primary objective of Phase 1 is to evaluate the safety of KTE-X19.  
The primary objective of Phase 2 is to evaluate the efficacy of KTE-X19, as measured by the 
overall complete remission rate defined as complete remission (CR) and complete remission with 
incomplete hematologic recovery (CRi) in adult subjects with relapsed/refractory B-precursor 
acute lymphoblastic leukemia (r/r ALL).  Secondary objectives will include assessing the safety 
and tolerability of KTE-X19, additional efficacy endpoints, and change in EQ-5D scores.


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2.
DISEASE BACKGROUND AND RATIONALE
2.1.
Overview of ALL and Epidemiology
Acute lymphoblastic leukemia is a heterogeneous group of lymphoid disorders that results from 
the clonal proliferation of immature lymphocytes of B-cell or T-cell lineage in the blood, bone 
marrow, and other organs.  The disease occurs with a bimodal age distribution, with 60% of 
cases diagnosed in patients less than 20 years old, and 25% of cases diagnosed at age 45 years or 
greater.  In the United States there are approximately 6,000 new ALL cases diagnosed per year, 
of which 2,500 are in adults.  While 5-year survival rates are 80-90% in children, less than 25% 
of adults achieve long-term survival, and the majority of the 1,400 ALL deaths per year in the 
United States are in adults {National Comprehensive Cancer Network 2014, Siegel 2014}.  
While initial CR rates in adults are high (80-90%) and the median duration of first remission in 
most studies is 18 months or longer, most patients eventually experience relapse {Kantarjian 
2004, Kantarjian 1994, Larson 1995, Rowe 2005}.  Outcomes in the second-line and beyond 
setting with chemotherapy are poor with CR rates of approximately 20-40%, being lower in 
patients with relapse within 12 months of initial response, and overall survival (OS) being 
approximately 6 months, making the relapsed/refractory setting the area of greatest unmet need 
in ALL {Faderl 2011, Fielding 2007, Kantarjian 2003, O'Brien 2013, Tavernier 2007, Thomas 
1999}. 
2.2.
Diagnosis and Subtyping of ALL
Diagnosis of ALL requires at least 20% lymphoblasts in the bone marrow {Harris 1999}.  ALL 
is then further classified into 1 of 3 major subtypes by immunophenotyping:  B-precursor ALL 
(70%), mature B-cell ALL (Burkitt lymphoma; 5%), and T-cell ALL (25%).  B-cell ALLs are 
generally CD10+, CD19+, and CD79a+, although precursor B-cell ALLs may be CD10-.  Mature 
B-cell ALLs additionally express surface immunoglobulin (Ig).  T-cell ALLs express T-cell 
markers such as CD3, CD4, and CD8.  The 3 immunophenotypic subtypes are associated with 
non-overlapping prognoses and treatments making the classification clinically relevant {National 
Comprehensive Cancer Network 2014}.  B-precursor ALL comprises the majority of all adult 
ALL cases.
2.3.
Philadelphia Positive vs. Negative ALL
Approximately 20-30% of adults and a small percentage of children with ALL are Philadelphia 
chromosome positive (Ph+), and the majority of Ph+ cases are of B-cell lineage {Lee 2011}.  Ph+ 
status confers poor prognosis, with a 5-year event-free survival (EFS) rate of 36% vs 16% and an 
OS rate of 41% vs. 22% in Philadelphia chromosome negative (Ph-) vs. Ph+ patients {Moorman 
2007}.  Ph+ status also allows for additional treatment with Abl tyrosine kinase inhibitors (TKIs) 
such as imatinib or dasatinib.  
2.4.
Treatment and Prognosis
Several anti-neoplastic agents are given in varying doses and schedules based on regional 
preferences and patient tolerability in 3 distinct phases for 1st line treatment: induction, 
intensified consolidation, and maintenance.  Central nervous system (CNS) prophylaxis 


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accompanies induction and consolidation.  The goals of treatment are to reconstitute normal 
hematopoiesis, prevent emergence of resistant subclones, eliminate minimal residual disease, and 
provide prophylaxis to sanctuary sites.  Stem cell transplant also plays a role in the management 
of ALL, and tyrosine kinase inhibitors are added to chemotherapy and transplant regimens in 
patients with Ph+ disease.
2.4.1.
First-line Treatment
Most first-line regimens are a variation of either the Berlin-Frankfurt-Münster/Children’s 
Oncology Group (BFM/COG) regimens, which include a combination of vincristine, an 
anthracycline, a corticosteroid, and L-asparaginase, or the Cancer and Leukemia Group B 
(CALGB) regimens, which include the 4 drug classes above plus cyclophosphamide {Larson 
1995, Rowe 2005}.  A TKI such as imatinib is included in the treatment regimen for patients 
with Ph+ disease.  Dexamethasone appears to decrease the risk of CNS relapse and improve EFS 
compared to prednisone, but at the risk of increased toxicity and no OS advantage {Mitchell 
2005, Pui 2006}.  The hyper-CVAD regimen which has demonstrated efficacy in ALL is a 
variation on the CALGB regimen with alternating regimens of hyperfractionated 
cyclophosphamide, vincristine, doxorubicin, and dexamethasone with high-dose methotrexate 
and cytarabine {Kantarjian 2004}.  First-line regimens yield CR rates of 80-90% in adults.  
Despite the high CR rates and a median duration of first remission of at least 18 months, most 
patients eventually relapse.  
2.4.2.
Second-line and Beyond Treatment
The salvage setting represents the area of greatest need in adult ALL given the poor outcomes 
achieved with chemotherapy in adults who have relapsed or refractory ALL.  Second-line 
chemotherapy yields remissions in about 20-40% of patients, with the remission rate being lower 
in patients who relapse within 12 months of an initial response (Table 1).  
In the third line and beyond setting, complete remissions with chemotherapy are seen in at most 
20% of patients, and the majority of remissions are short lived {Faderl 2011, Fielding 2007, 
Kantarjian 2003, O'Brien 2013, Tavernier 2007, Thomas 1999}.  Although long-term disease 
free survival (DFS) rates of autologous stem cell transplantation (ASCT) are superior to 
chemotherapy in the salvage setting (approximately 40% vs 20%), only 30-40% of patients who 
achieve a second CR are eligible for SCT, and fewer than half of the patients who achieve a 
second CR have enough time prior to relapse to make it to transplant {Herzig 1987, Kolb 2009, 
Terwey 2009}, with rates as low as 5% in adults being reported in some series {Thomas 1999}.  
In December 2014, the bispecific CD19-directed CD3 T-cell engaging agent blinatumomab was 
granted accelerated approval in the US for the treatment of Ph- relapsed or refractory B-cell 
precursor ALL {BLINCYTO 2017}.  The approval was granted based primarily on findings 
from a single-arm study of 185 evaluable patients with r/r B-precursor ALL (relapsed with first 
remission duration of ≤12 months in first salvage or relapsed or refractory after first salvage 
therapy or relapsed within 12 months of SCT).  CR was achieved in 32% of patients, and an 
additional 9% had CRh.  The majority of responses (81%) occurred within cycle 1 of treatment, 
75% of those with CR/CRh had an minimum residual disease (MRD)-negative response, and the 
SCT rate among those who achieved CR/CRh was 39%.  Duration of response/relapse-free 
survival in patients who had CR/CRh was 5.9 months.  Results from a second study of 
blinatumomab, a Phase 3 trial which randomized adults with r/r ALL 2:1 to blinatumomab 


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versus 1 of 4 standard of care (SOC) chemotherapy regiments, have also recently been reported.  
A total of 405 patients were randomized, and a prespecified interim analysis occurred after 
248 deaths.  Median OS was 7.8 months (95% CI: 5.7, 10.0) for blinatumomab and 4.0 months 
(95% CI: 2.9, 5.4) for SOC (p=.011; hazard ratio=0.71), surpassing the prespecified boundary p 
value of 0.0183.  Based on these results, this study was terminated early upon the 
recommendation of the study’s Data Safety Monitoring Board {Topp 2016}.  No studies have 
yet reported the outcomes of patients in the post-blinatumomab setting.
Table 1 below summarizes representative data in the salvage setting for adult ALL.  Given the 
promising early data for chimeric antigen receptor (CAR) T-cell therapy in r/r ALL (see 
Section 2.6), this trial evaluates KTE-X19 in this difficult setting.  
Table 1.
Complete Response (CR) Rate in Adult B-Precursor Acute 
Lymphoblastic Leukemia (B-ALL) in the Relapsed/Refractory Setting
Trial/Reference 
Treatment
Criteria
N
CR rate
Second line chemotherapy (relapsed or refractory after initial therapy for de novo disease)
Thomas Cancer 1999
Various 
chemotherapy or 
SCT regimens
Primary refractory (24%) 
or primary relapsed (76%) 
disease
314
31% overall 
22% for patients with 1st CR of 
duration 1-11.9 months (n=146)
41% for patients with first CR of 
duration >12 months (n=93)
20% for Ph+ (n=55)
34% for primary refractory (n=75)
Tavernier Leukemia 
2007
Various systemic 
or SCT regimens
Relapsed or refractory 
after initial therapy, Ph-
Relapsed or refractory 
after initial therapy, Ph+
340
81 
46% 
37%  
Welborn Am J Hema 
1994
Various 
chemotherapy 
regimens
Relapsed or refractory 
ALL (primarily second 
line patients)
609
34%
Faderl Clin 
Lymphoma Myeloma 
Leuk 2011
hCVAD
Refractory (11%) or 
relapsed (89%; 76% of all 
patients in 1st relapse) 
90
46% (median CR1 of responders = 
16 months)
Third line or beyond chemotherapy
Kantarjian Blood 
2003
Clofarabine
2nd or subsequent salvage
8
13%
Advani Br J 
Haematol 2010
Clofarabine+ 
cytarabine
Patients in ≥ 2nd relapse
16
19% (CR/CRi)A
O’Brien JCO 2013
Liposomal 
vincristine sulfate
Ph- ALL in 2nd or greater 
relapse
65
20% (CR/CRi)A
Novel targeted agents
Blinatumomab USPI
Blinatumomab
Relapsed/refractory 
B-precursor ALL
185
32% CR
9% CRhB
Kantarjian NEJM 
2016
Anti-CD22-
calecheamicin 
(inotuzumab 
oogamicin)
Relapsed and refractory 
ALL
49 (46 
adults)
36% CR
45%CRiA
OS HR 0.77 (97.5% CI, 0.58-1.03) 
inotuzumab vs. chemotherapy 
A
Complete remission with incomplete hematologic recovery (CRi)
B
Complete remission with partial hematologic recovery (CRh)
C
Complete marrow response (CMR)


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2.4.3.
Minimal Residual Disease (MRD)
Several studies have shown that the achievement of a minimum residual disease (MRD)-negative 
response (<0.01% lymphoblasts in the bone marrow) with ALL treatment is associated with 
prolonged leukemia remission in both pediatric and adult ALL patients {Campana 2010, 
Cazzaniga 2011}.  However, not all subjects who achieve a morphological complete remission 
achieve a MRD-negative remission.  In a large study by the Children’s Oncology Group 
randomizing patients to different induction and maintenance regimens, 1788 of 2422 (74%) of 
subjects who had a remission (<10% bone marrow blasts) achieved MRD-negative status 
{Borowitz 2015}.  Treatment with the bispecific T cell engager blinatumomab produces a 
similar proportion of MRD-negative responses, 8 of 14 (53%) pediatric patients with a CR had 
an MRD-negative response {von Stackelberg 2016}.  Minimum residual disease-negative rates 
are similar in adults.  With blinatumomab, 60 of 73 (82%) adult patients who achieved a CR or 
CRh had an MRD-negative response.
2.5.
Study Rationale
Most advanced cancers eventually become refractory to conventional therapies and new 
treatment modalities are needed.  Immunotherapy, which is based on the enhancement of an 
immune response against the tumor, is a promising approach to treating many cancer types.  
T cells play an important role in destroying diseased cells throughout the body.  Studies with 
immune checkpoint inhibitors and tumor infiltrating lymphocytes have demonstrated the 
potential of T cells to treat cancer.  T cells need to possess the appropriate specificity for a tumor, 
be present in sufficient numbers, and overcome any local immunosuppressive factors to be 
effective.  Engineered T cells are a promising approach for cancer therapy {Kershaw 2013}.
Engineered Autologous Cell Therapy (eACT™) is a process by which a patient’s own T cells are 
collected and subsequently genetically altered to recognize and target antigens expressed on the 
cell surface of specific malignancies {Kochenderfer 2013}.  The ability to genetically engineer 
human T cells and use them to mediate cancer regression in patients has been demonstrated in a 
number of studies {Davila 2014, Lee 2015, Maude 2014} and has opened possibilities for the 
treatment of patients with a wide variety of cancer types including B-cell malignancies 
expressing the CD19 antigen.
Given the poor outcomes which have been achieved to date in adults with r/r ALL (Table 1), this 
trial will enroll adult subjects with r/r B-precursor ALL as evidenced by failure to achieve or 
maintain a response to prior systemic therapy, or by recurrence after allogeneic SCT.  Patients 
with T-cell lineage ALL will not be enrolled since their malignancies are CD19- and will likely 
not respond to a CD19 directed agent.  
2.5.1.
CD19 and Expression
CD19 is a 95 kD transmembrane protein expressed only in the B-cell lineage. It is expressed in 
all normal B cells starting at the pre-B cell stage until the final differentiation stage and is not 
expressed in pluripotent hematopoietic stem cells or most plasma cells.  The pattern of CD19 
expression is maintained in B-cell malignancies including all subtypes of B-cell non-Hodgkin 
lymphoma (NHL), chronic lymphocytic leukemia (CLL), and non T-cell acute lymphoblastic 
leukemia (ALL) {Blanc 2011} with the exception of multiple myeloma.


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2.5.2. 
Anti-CD19 CART-cell Product 
Anti-CD19 CART cells are autologous human T cells that have been engineered to express an 
extracellular single chain variable :fragment (scFv) with specificity for CD19 linked to an 
intracellular signaling paii comprised of signaling domains from CD28 and CD3s molecules 
atTanged in tandem. KTE-X19 is an anti-CD19 CART cell product being developed by Kite 
Phaim a under ZUMA-3. 
The CAR vector constmct utilized in KTE-X19 is identical to the one used in National Cancer 
Institute (NCI) protocols (Smge1y Branch protocol 09-C-0082; IND 13871; Pediatric Branch 
(Protocol 12-C-0112G; IND: 14985). Refer to the cmTent KTE-X19 1B for additional 
description of the T-cell product. 
2.6. 
Clinical Experience with Anti-CD19 CART Cells in Studies Conducted at 
the National Cancer Institute (NCI) 
The same CAR construct used in KTE-X19-103 was previously evaluated at the NCI in children 
and young adults with r/r ALL {Lee 2015}; (clinicalti·ials.gov number NCT01593696), and in 
adults with r/r B-cell malignancies {Kochenderfer 2015}; ( clinicalti·ials.gov number 
NCT00924326). 
Refer to the cmTent KTE-X19 IB and publications cited for details on the study design and the 
safety and efficacy outcomes observed in these studies. 
2.7. 
KTE-C19-101 ZUMA-1 Experience 
ZUMA-I is a Phase 1-2 multicenter, open-label study evaluating the safety and efficacy of 
KTE-C19 in adult subjects with refracto1y DLBCL, PMBCL, and transfonned folliculai· 
lymphoma (TFL). The primaiy analysis for the study, which has been completed, was based on 
analysis of the data from 92 subjects in the phase 2 po1i ion of the study who had the oppo1iunity 
to be followed for at least 6 months after infusion of KTE-C19. The study met its primaiy 
endpoint: the objective response rate per International Working Group 2007 criteria { Cheson 
2007} in these 92 subjects was 82% (95% CI: 72%, 89%), which was significantly higher than 
the pre-specified conti·ol rate of 20% (p < 0.0001; {Locke 2017} ). 
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Refer to the current KTE-C19 IB for a summary of the safety and efficacy findings from this 
study.  
2.8.
KTE-X19-103 ZUMA-3 Phase 1 Experience
ZUMA-3 is a study of KTE-X19 in adults with r/r ALL (see Section 3).  The DLT evaluation 
period of the study was completed with no DLTs observed in the 2 x 106 anti-CD19 CAR T 
cells/kg dose cohort.  Additional subjects have been enrolled and treated in the phase 1 portion of 
the study at 1 x 106 anti-CD19 CAR T cells/kg and 0.5 x 106 anti-CD19 CAR T cells/kg.  
Forty-five patients were dosed in the Phase 1 portion of study across the 3 dose levels. Based on 
the risk-benefit ratio observed, the dose of 1 x 106 anti-CD19 CAR T cells/kg was considered the 
recommended Phase 2 dose.
Refer to the current KTE-X19 IB for a summary of the safety.  


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3.
KTE-X19-103 STUDY DESIGN
3.1.
General Study Design
ZUMA-3 is a Phase 1/2, multicenter, open-label study evaluating the safety and efficacy of 
KTE-X19 in adult subjects with relapsed or refractory B-precursor ALL. In this study, relapsed 
or refractory is defined as one of the following:  primary refractory; first relapse following a 
remission lasting ≤ 12 months; relapsed or refractory after second-line or higher 
therapy;  relapsed or refractory after allogenic SCT (provided the transplant occurred ≥ 100 days 
prior to enrollment and that no immunosuppressive medications were taken ≤ 4 weeks prior to 
enrollment). 
During Phase 1, approximately 3-12 subjects with high burden [M3 marrow (>25% leukemic 
blasts) or ≥1000 blasts/mm3 in the peripheral circulation] r/r ALL disease who are evaluable for 
DLT will be assessed to evaluate the safety of KTE-X19.  A 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 in Phase 1 or proceeding to Phase 2 based on the 
incidence of DLTs and overall safety profile of KTE-X19.  Additionally, approximately 
40 subjects with high or low burden disease may be enrolled to further assess safety (see 
Figure 1 and Section 9.6).  
During Phase 2, approximately 50 subjects in the mITT set will be assessed to evaluate the 
efficacy and safety of KTE-X19.  
In total, up to approximately 100 subjects may be enrolled and treated with KTE-X19 in the 
study in Phase 1 and 2 combined (see Section 9.6 and Section 10.5).  
During Phase 2, one interim and one primary analysis will be performed.  The interim analysis is 
for safety only and will be performed by an independent DSMB after 20 Phase 2 subjects have 
been treated with KTE-X19 and had the opportunity to be followed for 30 days after the 
KTE-X19 infusion (see Section 10.7).  Additional interim analyses for safety may be requested 
by the DSMB.  
The primary analysis will occur when the overall study enrollment is complete and the last 
treated subject in the mITT set has had the opportunity to complete the month 6 disease 
assessment (see Section 10.8).  
Each subject will provide consent and be evaluated for study participation.  Once deemed 
eligible and enrolled into the study, each subject will follow the same study treatment schedule 
and procedural requirements, independent of the phase of the study, and proceed through the 
following study periods:

Screening period

Enrollment/Leukapheresis period

Bridging chemotherapy and CSF prophylaxis period


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
Conditioning chemotherapy period

Investigational Product (IP) treatment period

Post treatment assessment period

Long term follow-up period
For study requirements assigned to each study period, refer to the schedule of assessments 
(SOA) and Section 7 for details.  A study schema is drawn out and described at the end of the 
protocol synopsis section.
Figure 1.
Phase 1 Dosing
3.2.
Participating Sites
Approximately 35 centers located in North America, Europe, and potentially other regions will 
participate in this study.  During the conduct of the study, additional regions, countries or sites 
may be added as necessary.
Sites that do not enroll a subject within 4 months of site activation may be considered for 
closure.
3.3.
Number of Subjects
Participants in this trial will be referred to as “subjects”.  Up to approximately 100 subjects may 
be enrolled into the entire study in order to obtain 3-12 subjects evaluable for DLT in the Phase 1 
portion, up to approximately 40 additional Phase 1 subjects, and approximately 50 subjects in the 
mITT set in the Phase 2 portion of the study.  
Proceed to 
Phase 2 
Additional subjects 
at 2xl06, lxl06 
and/ or 0.Sxl06 
anti-CD19 CART 
cells/kg 
Proceed to 
Phase 2 


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It should be noted that Kite Pharma may choose to close enrollment at any time.  Refer to the 
statistical considerations section of the protocol for sample size estimations.
3.4.
Replacement of Subjects
Subjects will continue to be enrolled until the specified numbers of subjects are attained in the 
DLT evaluable (Phase 1) and mITT sets (Phase 2).  
Subjects who have not received the required dose of KTE-X19 in order to be included in DLT 
evaluable set will be retained in the analyses of disposition and safety, where appropriate (see 
Section 10.5). 
3.5.
Study Duration
3.5.1.
Study Duration for Individual Subjects 
The duration of participation for individual subjects will vary depending on a subject’s screening 
requirements, response to treatment, survival, and, if applicable, timing of transition to the 
separate Long-term Follow-up (LTFU) study, KT-US-982-5968 (refer to section 3.5.3). 
The need for prolonged follow-up is based on the potential persistence of gene transfer vectors in 
treated subjects.
3.5.2.
Completion of Study
Completion of the study is defined as the time at which every subject has completed at least 24 
months of assessments, is considered lost to follow-up, withdraws consent, or dies. Upon 
activation of KT-US-982-5968 LTFU study at the subject’s study site, subjects who received 
infusion of KTE-X19 will be offered the opportunity to complete LTFU assessments under the 
KT-US-982-5968 protocol.  
3.5.3.
Long-term Follow-up Period
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 as defined in KT-US-
982-5968, presence of replication-competent retrovirus (RCR) and/or insertional mutagenesis for 
up to 15 years from the time of KTE-X19 infusion (also refer to section 7.11.9)
In KT-US-982-5968, subjects will continue assessments at timepoints contiguous with the LTFU 
timepoints in this study. 


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4.
SUBJECT SCREENING AND ENROLLMENT
All subjects must sign and date the IRB/IEC approved consent form before initiating any study 
specific procedures or activities that are not part of a subject’s routine care.  Refer to Section 7 
for details.
Each subject who enters the screening period will receive a unique subject identification number 
at the time of consent [refer to the Investigational Product Manual (IPM)].  This number will be 
used to identify the subject throughout the study and must be used on all study documentation 
related to the subject.
Furthermore, the subject identification number must remain constant throughout the entire 
clinical study, it must not be changed after enrollment or if the subject is rescreened. 
Once a subject commences leukapheresis, the subject will be considered enrolled into the study.


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5.
SUBJECT ELIGIBILITY
5.1.
Inclusion Criteria
101)
Relapsed or refractory B-precursor ALL defined as one of the following:

Primary refractory disease

First relapse if first remission ≤ 12 months

Relapsed or refractory disease after two or more lines of systemic therapy

Relapsed or refractory disease after allogeneic transplant provided subject is at least 
100 days from stem cell transplant at the time of enrollment and off of 
immunosuppressive medications for at least 4 weeks prior to enrollment
102)
Morphological disease in the bone marrow (> 5% blasts)
103)
Subjects with Ph+ disease are eligible if they are intolerant to tyrosine kinase inhibitor 
(TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 
2 different TKIs
104)
Age 18 or older
105)
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
106)
ANC ≥ 500/µL unless in the opinion of the PI cytopenia is due to underlying leukemia 
and is potentially reversible with leukemia therapy 
107)
Platelet count ≥ 50,000/µL unless in the opinion of the PI cytopenia is due to underlying 
leukemia and is potentially reversible with leukemia therapy 
108)
Absolute lymphocyte count ≥ 100/µL
109)
Adequate renal, hepatic, pulmonary and cardiac function defined as:

Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min 

Serum ALT/AST ≤ 2.5 x ULN (upper limit normal) 

Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert’s syndrome.

Left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial effusion 
as determined by an ECHO, no NYHA class III or class IV functional classification, 
and no clinically significant arrhythmias

No clinically significant pleural effusion

Baseline oxygen saturation > 92% on room air


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110)
Females of childbearing potential must have a negative serum or urine pregnancy test 
111)
In subjects previously treated with blinatumomab, CD19 tumor expression on blasts 
obtained from bone marrow or peripheral blood must be documented after completion of 
the most recent prior line of therapy.  If CD19 expression is quantified, then blasts must 
be ≥ 90% CD19 positive.
5.2.
Exclusion Criteria
201)
Diagnosis of Burkitt’s leukemia/lymphoma according to WHO classification or chronic 
myelogenous leukemia lymphoid blast crisis
202)
History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, 
cervix, bladder, breast) unless disease free for at least 3 years 
203)
History of severe hypersensitivity reaction to aminoglycosides or any of the agents used 
in this study
204)
CNS abnormalities

Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample 
of CSF with ≥ 5 WBCs per mm3 with or without neurological changes, and 

Presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a sample 
of CSF with <5 WBCs per mm3 with neurological changes 
Note: Subjects with CNS-1 (no detectable leukemia in the CSF) and those with 
CNS-2 without clinically evident neurological changes are eligible to participate in 
the study. 

History or presence of any CNS disorder such as a seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with 
CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral 
edema  
205)
History of concomitant genetic syndrome associated with bone marrow failure such as 
Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome
206)
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or 
other clinically significant cardiac disease within 12 months of enrollment
207)
History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of 
enrollment.  
208)
Primary immunodeficiency 
209)
Known infection with HIV, hepatitis B or hepatitis C virus.  A history of hepatitis B or 
hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or 
nucleic acid testing.


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210)
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring 
antimicrobials for management.  Simple UTI and uncomplicated bacterial pharyngitis are 
permitted if responding to active treatment and after consultation with the Kite Medical 
Monitor
211)
Prior medication: 

Salvage systemic therapy (including chemotherapy, TKIs for Ph+ ALL, and 
blinatumomab) within 1 week or 5 half-lives (whichever is shorter) prior to 
enrollment 

Prior CD19 directed therapy other than blinatumomab

History of CTCAE grade 4 neurologic event or grade 4 CRS {Lee 2014} with prior 
CD19-directed therapy

Treatment with alemtuzumab within 6 months prior to enrollment, clofarabine or 
cladribine within 3 months prior to enrollment, or PEG-asparaginase within 3 weeks 
prior to enrollment

Donor lymphocyte infusion (DLI) within 28 days prior to enrollment

Any drug used for GVHD within 4 weeks prior to enrollment (eg, calcineurin 
inhibitors, methotrexate, mycophenolyate, rapamycin, thalidomide), or 
immunosuppressive antibody used within 4 weeks prior to enrollment (eg, anti-CD20, 
anti-tumor necrosis factor, anti-interleukin 6 or anti-interleukin 6 receptor)

At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory 
immune checkpoint molecule therapy prior to enrollment (eg, ipilimumab, 
nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists etc) 

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 enrollment
212)
Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling 
Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter).  Ommaya 
reservoirs and dedicated central venous access catheters such as a Port-a-Cath or 
Hickman catheter are permitted 
213)
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute 
or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment 
214)
Live vaccine ≤ 4 weeks prior to enrollment
215)
Women of child-bearing 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


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216)
Subjects of both genders of child-bearing potential who are not willing to practice birth 
control from the time of consent through 6 months after the completion of KTE-X19
217)
In the investigator’s judgment, the subject is unlikely to complete all protocol-required 
study visits or procedures, including follow-up visits, or comply with the study 
requirements for participation
218)
History of autoimmune disease (eg, Crohns, rheumatoid arthritis, systemic lupus) 
resulting in end organ injury or requiring systemic immunosuppression/systemic disease 
modifying agents within the last 2 years


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6.
 PROTOCOL TREATMENT 
6.1.
Treatment Terminology
The following terms will be used to describe and define protocol treatment: 

Bridging chemotherapy refers to treatment used to control a subject’s disease prior to 
conditioning chemotherapy. 

CSF prophylaxis will be administered prior to infusion of conditioning chemotherapy.

The Conditioning chemotherapy regimen used for this study will be fludarabine and 
cyclophosphamide.  

The investigational product for this study is named KTE-X19.  
6.2.
Leukapheresis (within approximately 5 days of eligibility confirmation)
Before leukapheresis commences, the criteria outlined in Section 7.11.3 must be met.
Subjects will undergo leukapheresis to obtain leukocytes (white blood cells) for the manufacture 
of KTE-X19.  Leukapheresed cells obtained from subjects at participating centers will be 
shipped to the Cell Processing Facility (CPF) overnight as described in the IPM.    
Mononuclear cells will be obtained by leukapheresis (approximately 12-15 liter apheresis with a 
goal to target approximately 5-10 x 109 mononuclear cells).  The leukapheresed cells are then 
packaged for expedited shipment to the CPF as described in the IPM.    
Upon arrival at the CPF, each subject’s leukapheresed product will be processed to positively 
select for T cells, which are then activated and transduced with a retroviral vector to introduce 
the CAR gene.  The engineered T cells are then further expanded and cryopreserved to generate 
the investigational product per CPF standard operating procedures.  After KTE-X19 has been 
manufactured and has passed release criteria, it will be shipped to the treating facility and must 
be stored per the IPM (see Section 6.6).  
See Section 6.8 for excluded medications prior to leukapheresis.
6.3.
Bridging Chemotherapy 
Bridging therapy may be administered after leukapheresis and prior to conditioning 
chemotherapy at the investigators discretion.  Bridging chemotherapy is recommended for all 
subjects particularly those subjects with high disease burden at baseline [M3 marrow (>25% 
leukemic blasts) or ≥ 1000 blasts/mm3 in the peripheral circulation].  If prescribed, bridging 
chemotherapy must be administered after leukapheresis and completed at least 7 days or 5 half-
lives, whichever is shorter, prior to initiating conditioning chemotherapy.  


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Allowed bridging chemotherapy regimens are outlined in Table 2.  Doses listed are 
recommended, and can be adjusted for age/comorbidities or per local or institutional guidelines. 
Table 2.
Bridging Chemotherapy Regimens
Bridging Chemotherapy Regimen a
Attenuated VAD: Vincristine non-liposomal 
(1-2 mg IV weekly) or liposomal (2.25 mg/m2 
IV weekly), and dexamethasone 20-40 mg IV or 
PO daily x 3-4 days per week.  Optional 
doxorubicin 50 mg/m2 IV x 1 (first week only).
DOMP: Dexamethasone 6 mg/m2/day PO (or IV) divided 
BID days 1-5, vincristine 1.5 mg/m2 (maximum dose 2 mg) 
IV on day 1, methotrexate 20 mg/m2 PO weekly, 6-MP 50-
75mg/m2/day PO daily
Mercaptopurine (6-MP): 50-75 mg/m2/day by 
mouth (administer at bedtime on an empty 
stomach to improve absorption)
Attenuated FLAG/FLAG-IDA: fludarabine 30 mg/m2 IV days 
1-2, cytarabine 2 g/m2 IV days 1-2, G-CSF 5 µg/kg SC or IV 
starts on day 3 and can continue until day before the start of 
conditioning chemotherapy.  With or without idarubicin 
6 mg/m2 IV days 1-2.
Hydroxyurea:  Doses titrated between 
15-50 mg/kg/day (rounded to the nearest 500 mg 
capsule and given as a single daily oral dose on 
a continuous basis)
Mini-hyper CVAD (courses A and/or B):
Course A: Cyclophosphamide 150 mg/m2 q 12 hrs x 3 days, 
dexamethasone 20 mg/d IV or PO daily days 1-4 and 11-14, 
vincristine 2 mg IV x 1
Course B: methotrexate 250 mg/m2 IV over 24h on day 1,  
cytarabine 0.5 g/m2 IV q12h x 4 doses on days 2 and 3.
a
Use of a TKI in combination with any of the above regimens is allowed for subjects with Ph+ ALL and Ph-like ALL
Given subjects with r/r ALL can have rapidly progressive disease and clinical deterioration, 
bridging chemotherapy allows physicians to provide standard of care to subjects in the period 
between leukapheresis and manufacturing of KTE-X19.  Based on the published data {Davila 
2014, Lee 2014, Maude 2014}, decreased tumor burden is additionally associated with less 
cytokine release syndrome (CRS).
Bridging therapy should be administered per institutional guidelines.  
Refer to the current product label for guidance on packaging, storage, preparation, 
administration, including necessary dose reductions for organ dysfunction, and toxicity 
management associated with the administration of chemotherapy agents.
6.4.
CSF Prophylaxis 
All subjects will receive CSF prophylaxis consisting of an intrathecal regimen according to 
institutional or national guidelines (eg, methotrexate 12 to 15 mg, cytosine arabinoside 40 mg, or 
dexamethasone 4 mg or equivalent steroid dose).  
CSF prophylaxis will be administered any time during screening (eg, at time of screening lumbar 
puncture) through 7 days prior to KTE-X19 infusion.  
Subjects who are enrolled with CNS-2 disease at baseline must receive CSF prophylaxis after 
leukapheresis and at least 7 days prior to KTE-X19 infusion, unless otherwise approved by the 
Kite Medical Monitor.   


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Multiple doses of CSF prophylaxis can be given per investigator discretion in accordance with 
institutional guidelines, but at least 7 days must pass between the last dose of CSF prophylaxis 
and KTE-X19 infusion.  
Additional CSF prophylaxis may be given post-KTE-X19 infusion per investigator discretion in 
accordance with institutional guidelines, but should be avoided for at least 8 weeks after 
KTE-X19 infusion if possible.  
Should a subject have an Ommaya reservoir and there is no evidence of blockage of CSF flow 
from the spinal canal, administration of CSF prophylaxis through the reservoir is acceptable. 
6.5.
Conditioning Chemotherapy 
Conditioning chemotherapy refers to fludarabine and cyclophosphamide used for 
lymphodepletion prior to administration of KTE-X19.  Subjects will receive conditioning 
chemotherapy from Day -4 through day -2.  
Conditioning chemotherapy will be supplied by the investigative site unless otherwise noted.
Refer to the current product label for guidance on packaging, storage, preparation, administration 
and toxicity management associated with the administration of chemotherapy agents.
The investigational medicinal product (KTE-X19) must be available before initiation of 
conditioning chemotherapy.
See Section 7.11.6.1 for conditioning chemotherapy procedures. 
6.5.1.
Fludarabine
Fludarabine phosphate 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.
6.5.2.
Cyclophosphamide
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent.  Following conversion to 
active metabolites in the liver, cyclophosphamide functions as an alkylating agent; the drug also 
possesses potent immunosuppressive activity.  The serum half-life after IV administration ranges 
from 3-12 hours; the drug and/or its metabolites can be detected in the serum for up to 72 hours 
after administration.  
6.5.3.
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 will be administered 
around the cyclophosphamide dose according to institutional standards.  


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6.5.4.
Rationale for Conditioning Chemotherapy Choice and Dose
The rationale for the conditioning chemotherapy regimen and dose selection is based on the 
Phase 1 study conducted at the Pediatric Oncology Branch at the NCI {Lee 2015}.  In this study, 
21 subjects (20 with ALL) were treated and all received the same fludarabine and 
cyclophosphamide schedule with a favorable benefit/risk profile.  
Consistent with the NCI protocol {Lee 2015}, the KTE-X19-103 study will use the same 
Conditioning chemotherapy regimen consisting of fludarabine at a dose of 25 mg/m2/day IV over 
30 minutes on Day -4, Day -3, Day -2 prior to KTE-X19 and cyclophosphamide at a dose of 
900 mg/m2/day IV over 60 minutes on Day -2 prior to KTE-X19.   Day -1 will be a rest day.  The 
3-day conditioning chemotherapy regimen may be administered in an outpatient setting in 
accordance with the daily dosing instructions outlined in Section 7.11.6.2. 
Following completion of each subjects’ conditioning chemotherapy regimen, subjects will 
receive their respective KTE-X19 infusion.  
6.6.
KTE-X19 
The IP for this study is KTE-X19.
Refer to the most current Investigator’s Brochure regarding KTE-X19 and clinical experience.  
This section contains general information and is not intended to provide specific instructions.  
Refer to the IPM for details and instruction on storage and administration of KTE-X19.  
KTE-X19 is supplied cryopreserved in cryostorage bags.  The product in the bag is slightly 
cloudy, with cream to yellow color.  The cryostorage bags containing KTE-X19 arrive frozen in 
a liquid nitrogen dry shipper.  The bags must be stored in vapor phase of liquid nitrogen and the 
product remains frozen until the subject is ready for treatment to assure viable live autologous 
cells are administered to the subject.  Several inactive ingredients are added to the product to 
assure viability and stability of the live cells through the freezing, thawing, and infusion process.
KTE-X19 is a subject-specific product and the intended subject will be identified by a unique 
subject ID number.  Upon receipt, verification that the product and subject-specific labels match 
the subject’s information (eg, initials, subject ID number) is essential.  Do not infuse the product 
if the information on the subject-specific label does not match the intended subject.  The volume 
of KTE-X19 infused, the thaw start/stop time, and KTE-X19 infusion start/stop time, will be 
noted in the subject medical record.  The product must not be thawed until the subject is ready 
for the infusion.  
To date, subjects have received doses of anti-CD19 CAR T cells ranging from 0.5 - 30 x 106 
anti-CD19 CAR T cells/kg.  There have been no instances of accidental overdose of subjects in 
this program.  In case of accidental overdose, treatment should be supportive.  Corticosteroid 
therapy may be considered if any dose is associated with severe toxicity (see Section 6.8 for 
more information related to corticosteroid use).


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6.6.1.
Rationale for KTE-X19 Dose
The rationale for the initial dose of KTE-X19 evaluated in ZUMA-3 (2 x 106 anti-CD19 CAR T 
cells/kg) was based on the DLT and MTD data generated from the 2 studies conducted at the 
Pediatric Oncology {Lee 2015} and Surgery Branch {Kochenderfer 2015} of the NCI.  
Additional doses evaluated in this study are further informed by emerging Phase 1 data (see 
Section 2.8).  
In the Pediatric Oncology Branch study, 4 pediatric subjects were enrolled and received a 
starting dose of 1 x 106 anti-CD19 CAR T cells/kg with no DLT observed.  The CAR T cell dose 
was then escalated to 3 x 106 anti-CD19 CAR T cells/kg.  At this higher dose, 4 pediatric 
subjects were treated and 2 subjects experienced a CRS DLT (one Grade 3 and one Grade 4 
event). Based on these observations, the study defined the MTD at 1 x 106 anti-CD19 CAR T 
cells/kg for the remainder of the study. 
In the Surgery Branch adult study, as of November 30, 2014, Group 3 enrolled 11 adult subjects, 
where the first 7 and last 4 subjects received anti-CD19 CAR T cell infusion of 1 x 106 
anti-CD19 CAR T cells/kg and 2 x 106 anti-CD19 CAR T cells/kg, respectively and the 
benefit/risk profile remained favorable.   
In the ZUMA-3 study, the initial 6 subjects were treated at 2 x 106 anti-CD19 CAR T cell/kg, 
with a subsequent group of 14 subjects treated at 1 x 106 anti-CD19 CAR T cell/kg.  No DLTs 
were observed in the DLT evaluable set, no drop off was seen in efficacy between the 2 x 106 
anti-CD19 CAR T cell/kg and 1 x 106 anti-CD19 CAR T cell/kg KTE-X19 doses, and there was 
no clear difference in the safety profile (Section 2.8; {Shah 2016}).  These data suggested it may 
be possible to lower the KTE-X19 dose further without diminishing and potentially enhancing 
the risk:benefit profile of KTE-X19 in r/r ALL.  As a result, additional subjects were dosed at 
0.5 x 106 anti-CD19 CAR T cells/kg. The safety profile observed at the lower dose was 
considered manageable, however the efficacy was diminished compared to higher dose levels. 
Based on the safety/efficacy observations, the SRT decision was to explore the safety profile at 
the 1 x 106 anti-CD19 CAR T cell/kg with implementation of new toxicity management 
recommendations by enrolling additional subjects at this dose level. The new safety profile 
observed at the dose of 1 x 106 anti-CD19 CAR T cell/kg was considered favorable without 
significant decrease in efficacy, therefore the dose of 1 x 106 anti-CD19 CAR T cell/kg was 
considered the recommended Phase 2 dose.
For subjects weighing greater than 100 kg, a maximum flat dose of 2 x 108 or 1 x 108 or 0.5 x 108 
anti-CD19 CART cells may be administered.  See Sections 9.6 for details. If any problems 
related to the use of KTE-X19 or any products that support the successful delivery and infusion 
of KTE-X19 (eg, cryostorage bags, subject identification labels) required in this study are 
identified, refer to the instructions in the IPM for details).  
6.7.
Concomitant Therapy
Concomitant therapy refers to treatment that subjects receive during the conduct of the study.
Investigators may additionally prescribe any other concomitant medications or treatment deemed 
necessary to provide adequate supportive care, including growth factor support (eg, G-CSF) and 
routine anti-emetic prophylaxis and treatment except those medications listed in the excluded 
medication Section 6.8.  


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In subjects with Ph+ disease and who achieve CR, a TKI may be resumed 2 months after 
KTE-X19 infusion at the investigator discretion and in accordance with institutional guidelines.  
See Section 3, Table 2 for use of TKI’s during bridging chemotherapy.
The investigator is responsible for reporting all concomitant medications as follows in Table 3:
Table 3.
Reporting Requirements for Concomitant Medications
Subjects who are pre-
screen or screen-fails
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 from the 
date of the pre-
screening informed 
consent or screening 
informed consent 
through 30 days after 
the last study-specific 
pre-screening or 
screening procedure, 
respectively.

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 anti-cancer 
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.  
(excluding allogeneic SCT)

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.  
o
In subjects who received 
allogeneic SCT, only concomitant 
medications related to a KTE-
X19-related serious adverse event 
(SAE) will be recorded.  
Reporting of these concomitant 
medications will commence at the 
time the SCT preparative regimen 
commences.
See Section 6.9 regarding documentation of subsequent anticancer therapy.
6.8.
Excluded Medications
Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to 
leukapheresis and 5 days prior to KTE-X19 infusion.  
Systemic corticosteroids should be avoided as premedication in subjects for whom CT scans 
with contrast are contraindicated (ie, subjects with contrast allergy or impaired renal clearance).  
If possible, such subjects should undergo non-contrast CT scans or alternative imagine modality 
(such as MRI) instead. 


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Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months after 
KTE-X19 infusion, unless used to manage KTE-X19 related toxicities (Refer to the most current 
version of the IB; see Section 6.4).  Other medications which may interfere with evaluation of 
KTE-X19, such as non-steroidal anti-inflammatory agents should also be avoided for the same 
time 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.  If a subject requires the initiation of therapeutic anticoagulant 
doses prior to initiation of conditioning chemotherapy or prior to KTE-X19 infusion, then 
conditioning chemotherapy/KTE-X19 infusion must be held and the case discussed with the Kite 
Medical Monitor.
For subjects with Ph+ ALL, all TKIs must be stopped at least 1 week prior to KTE-X19 infusion, 
including but not limited to imatinib, dasatinib, and ponatinib.  In subjects who achieve CR, a 
TKI may be resumed 2 months after KTE-X19 infusion.   See Section 6.3, Table 2 for use of 
TKIs during bridging chemotherapy.
CSF prophylaxis may be given post-KTE-X19 infusion per investigator discretion in accordance 
with institutional guidelines, but should be avoided for at least 8 weeks after KTE-X19 infusion 
if possible.  
Treatment for the subject’s leukemia such as chemotherapy, immunotherapy, targeted agents, 
radiation, high dose corticosteroid, other than defined/allowed in this protocol, and other 
investigational agents are prohibited except as needed for treatment of disease progression after 
KTE-X19 infusion.  If permissibility of a specific medication/treatment is in question, contact 
the Kite Pharma medical monitor.
Medications with sedative properties should be avoided if possible in the setting of neurologic 
events (refer to the KTE-X19 IB).
6.9.
Subsequent Therapy 
Subsequent therapy administered after KTE-X19 infusion for a subject’s disease such as non-
study specified chemotherapy, immunotherapy, targeted agents, as well as stem cell transplant 
and radiation therapy will be recorded for all enrolled subjects until one of the following occurs:  
subject completes the long-term follow-up period, is considered lost to follow-up, withdraws 
consent, dies, or transitions to the KT-US-982-5968 LTFU study where subsequent therapy will 
continue to be recorded.
For subjects who are enrolled, but do not receive KTE-X19 infusion, any additional anti-cancer 
therapy will also be collected until the subject completes their participation in the current study, 
is considered lost to follow up, withdraws consent, or dies, whichever occurs first.


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6.10.
Toxicity Management
To date, the following important risks have been identified with KTE-X19: CRS, neurological 
events, infections, and cytopenias.  Refer to the current KTE-X19 IB for details regarding these 
events and management guidance.  
As the safety experience with KTE-X19 increases, the management guidance may be updated. 
Therefore, it is important that you always refer to the most current version of the KTE-X19 IB 
for guidance regarding managing KTE-X19 related toxicities. 
Additional information and management recommendations can also be found in the IB regarding 
important potential risks associated with KTE-X19 as well as possible complications associated 
with malignancy and cancer treatment.


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7.
STUDY PROCEDURES
Research staff should refer to the SOA for an outline of the procedures required.  The visit 
schedule is calculated from KTE-X19 infusion on Day 0. 
An overview of study assessments/procedures is outlined below.  A description for each period 
of the study is provided in Section 7.11.  Refer to the CRF completion guidelines for data 
collection requirements and documentation of study procedures.
7.1.
Informed Consent
Before a subject’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequate explanation of the study design, 
anticipated benefits and the potential risks.  Subjects should sign the most current Institutional 
Review Board/Independent Ethics Committee (IRB/IEC) approved Informed Consent form 
(ICF) prior to any study specific activity or procedure is performed.
The consent process and the subject’s agreement or refusal to participate in the study is to be 
documented in the subject’s medical records.  If the subject agrees to participate, the ICF is to be 
signed and personally dated by the subject and by the person who conducted the informed 
consent discussion.  The original signed ICF will be retained in accordance with institution 
policy and IRB/IEC requirements with a copy of the ICF provided to the subject.
All subjects who are enrolled into the study should be re-consented with any updated version of 
the IRB/IEC approved ICF if relevant to their participation in the study.
7.2.
Demographic Data
Demographic data will be collected 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 their possible association with subject safety and treatment effectiveness.
7.3.
Medical and Treatment History
Relevant medical history prior to the start of adverse event reporting will be collected.  Relevant 
medical history is defined as data on the subject’s concurrent medical condition that would be 
typically shared in a referral letter.  All findings will be recorded in the CRFs.
In addition to the medical history, all history related to the subject’s disease, treatment and 
response to treatment will be collected and must date back to the original diagnosis.
For subjects who are being referred from another clinic or institution to the participating research 
center, copies from the subject’s chart should be obtained.


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7.4.
Physical Exam, Vital Signs, Performance Status, and European Quality of 
Life-5 Dimensions (EQ-5D) 
Physical exams will be performed during screening and at times noted in the SOA.  Changes 
noted in subsequent exams when compared to the baseline exam will be reported as an adverse 
event. 
During KTE-X19 infusion/hospitalization, vital signs including blood pressure, heart rate, 
oxygen saturation, and temperature will be monitored before and after the KTE-X19 infusion and 
then routinely (every 4-6 hours) while hospitalized.  If the subject has a fever (temperature 
38.3oC or greater) at any time during hospitalization, vital signs will be monitored more 
frequently as clinically indicated.
Performance status as measured by the ECOG scale will be performed to quantify the subject’s 
general well-being and ability to perform activities of daily life.
The EQ-5D will be completed only for subjects participating in phase 2.  The EQ-5D will be 
completed at the timepoints outlined in the SOA prior to other study related procedures or 
assessments.  Subjects who are blind or illiterate may have the EQ-5D questions read to them by 
the study staff.  The study staff, however, cannot interpret any of the questions for the subject.  A 
subject may be exempt from completing the questionnaire if he or she is unable to read the 
questionnaire in one of the country languages available.
The EQ-5D is a 2 page generic patient questionnaire for assessing the overall health status of a 
subject.  The EQ-5D consists of a 5 dimension descriptive system including questions on 
mobility, self-care, usual activities, pain/comfort, and anxiety/depression and a visual analogue 
scale (EQ VAS) which allows the respondent to record health on a vertical scale (eg, best health 
to worst health) thus allowing a quantitative measure of health outcome.  
7.5.
Neurological Assessment 
Subject’s 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 should be reported as an adverse 
event per Section 9.
7.6.
Cardiac Function 
Each subject’s cardiac function as measured by ECHO will be assessed during the screening 
period to confirm study eligibility.  No evidence of pericardial effusion, as required by 
eligibility, will also be confirmed by ECHO.  
If the last chemotherapy regimen the subject received is not considered cardiotoxic, then an 
ECHO performed within 28 days prior to signing the consent may be used for eligibility.  


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If the last chemotherapy regimen the subject received is considered cardiotoxic, then an ECHO 
performed following the subjects last chemotherapy treatment and within 28 days prior to 
signing the consent may be used for confirmation of eligibility.
A baseline chest x-ray will be completed within 14 days before enrollment to confirm eligibility.
To establish a baseline, an ECG will be performed within 30 days before enrollment. 
7.7.
Lumbar Puncture 
CSF samples (ie, collected on or after informed consent) will be analyzed locally for disease 
assessment (see Section 7.8 for details regarding analytes).  A portion will be submitted to the 
central laboratory for disease assessment and toxicity evaluation.  Refer to refer to the KTE-X19 
IB regarding platelet support.
Should a subject have an Ommaya reservoir and there is no evidence of blockage of CSF flow 
from the spinal canal, withdrawal of the CSF sample through the reservoir is acceptable.
CSF samples will be collected at the following time points:

Baseline – a CSF result obtained within 30 days before enrollment will be acceptable for 
eligibility determination

At the time of CSF prophylaxis (this sample may be the same as the baseline sample)

For subjects with CNS-2 at baseline, a CSF sample is required at the time of first presumed 
response (ie, bone marrow blasts < 5%)

First onset of ≥ grade 2 neurological symptoms or as medically indicated

Additional evaluations of the CSF should be performed per institutional standard of care
CSF blast counts can be falsely increased in cases of traumatic lumbar puncture.  In this instance, 
the blast count should be adjusted using the following formula, and the corrected value entered 
into the CRF:  
𝑏𝑙𝑎𝑠𝑡(𝐶𝑆𝐹, 𝑡𝑟𝑢𝑒) = 𝑏𝑙𝑎𝑠𝑡 (𝐶𝑆𝐹, 𝑜𝑏𝑠𝑒𝑟𝑣𝑒𝑑) ― 𝑏𝑙𝑎𝑠𝑡 (𝑏𝑙𝑜𝑜𝑑) × 𝑅𝐵𝐶(𝐶𝑆𝐹)
𝑅𝐵𝐶(𝑏𝑙𝑜𝑜𝑑)
Subjects with CNS-2 will have a lumbar puncture performed at the screening visit for 
examination of CSF.  In addition, a lumbar puncture may be performed as applicable for subjects 
with new onset of a Grade 2 or higher neurologic event after KTE-X19 infusion
7.8.
Laboratory  
The below samples will be collected at the time points indicated in the SOA.  Additional samples 
(eg, blood, urine, other bodily fluids, tissue) may be collected as needed for further safety testing.    


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Local Laboratory Analysis:

Bone marrow evaluation for % blasts 

Cerebral spinal fluid (total protein, WBC, RBC, %blast by morphological assessment, and 
gram stain and culture if clinically indicated or for neurological event)

Sodium (Na), Potassium (K), Chloride (Cl), Total CO2 (bicarbonate), Creatinine, Glucose, 
Urea nitrogen (BUN) or Urea (if BUN not available), Albumin, Calcium (Ca) total, 
Magnesium total (Mg), Inorganic Phosphorus (P), Alkaline Phosphatase, ALT/GPT, 
AST/GOT, Total Bilirubin, Direct Bilirubin, LDH, Uric Acid (Note: Direct Bilirubin, LDH, 
and Uric Acid are recommended, not mandatory)

C-reactive protein 

Complete Blood Count with differential (5-part preferred, but 3-part will be acceptable)

Peripheral blast count recommended (see Section 7.11.6.3 regarding Day -4)

Absolute lymphocyte count (ALC)

CD3 count based on peripheral blood

CD19 immunophenotyping by flow cytometry or IHC using peripheral blood or bone 
marrow 
Note:  Surface CD19 expression should be measured by flow cytometry; IHC analysis is 
allowed if the bone marrow aspirate is a dry tap, inadequate or there were insufficient 
circulating blasts for flow cytometry.

A urine or serum sample will be collected for females of childbearing potential. If the 
screening pregnancy test is positive, the subjects should not be enrolled.  If a standard of care 
pregnancy test is collected during the course of the study, and the result is positive, the 
investigator should contact the Kite Pharma medical monitor for instructions.  If a female 
partner of a male subject becomes pregnant during the conduct of the study, it must be 
reported by contacting Kite Pharma Medical Monitor for instructions. 

For European Union (EU) sites, viral serologic tests (eg, HIV, hepatitis B, hepatitis C) will 
be carried out per institution guidelines and EU regulations. This may be done within the 
30 days prior to leukapheresis and/or on the day of leukapheresis (see Section 7.11.1).
Central Laboratory Analysis:

Bone marrow biopsy and aspirate samples collected for confirmation of diagnosis as well as 
disease assessment

Cerebral spinal fluid


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
Blood draws for cytokine levels and PBMCs (for the analysis of lymphocyte subsets, 
anti-CD19 CART cells, and replication-competent retrovirus [RCR] analysis) 

Serum samples will also be drawn for anti-KTE-X19 antibodies 

Peripheral blood

See central laboratory manual for details.
7.9.
Disease Assessments
7.9.1.
Bone Marrow Evaluation
Bone marrow aspirates and biopsies will be collected throughout the study per the protocol SOA 
and/or standard of care.  

Screening bone marrow evaluation:
If available, archival formalin-fixed paraffin embedded (FFPE) bone marrow block 
and/or slides used for the original diagnosis of ALL will be submitted to the central 
laboratory along with the pathology report.
A bone marrow aspirate and biopsy is required at screening and will be performed after 
the last dose of systemic chemotherapy and within approximately 14 days before 
enrollment to establish baseline disease.  
■
If there is a delay between when the screening bone marrow is performed and the 
apheresis, contact the Kite Medical Monitor for guidance on whether or not bone 
marrow evaluation needs to be repeated.  If a fresh bone marrow aspirate and biopsy 
was recently collected and properly stored prior to consent, then contact the Kite 
Medical Monitor to confirm if this sample is adequate for screening.  
In subjects who receive bridging chemotherapy, an additional bone marrow sample is 
required between the end of bridging chemotherapy and Day -4.  If bridging 
chemotherapy is not administered, then the additional bone marrow sample is not 
required, however, an assessment of peripheral circulating blasts is required (see 
Section 7.11.6.3 regarding requirement for peripheral blast count).  

On study bone marrow evaluations: 
A bone marrow aspirate will be required at all time points per the SOA to assess 
treatment response.  
■
For subjects who undergo a SCT, bone marrow evaluations are not required during 
the first 100 days post-SCT.  After 100 days, bone marrow evaluations should be 
performed at the next per protocol time point per the SOA.  If a subject has a bone 
marrow evaluation earlier than the next per protocol time point, then the bone marrow 
samples should be processed and submitted to the central laboratory per the central 
laboratory manual.  


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-103 
Amendment 7 
-
In addition to the bone man ow aspirate, a bone manow biopsy is required at Day -4 and 
Day 28. A bone manow biopsy at all other time points is recommended and should be 
perfo1med if standard of care. Note: Anytime the bone manow aspirate is a diy tap, then 
a bone maiTow biopsy is required. In the case of a diy tap, the bone maiTow biopsy will 
be used to detennine disease burden by immunohistochemical (IHC) analyses. The 
following markers will be analyzed by IHC: CDlO, CD19, CD20, CD34, Pax5 and TdT. 
-
Reminders: 
For subjects with a CR, collection and analysis of CSF is required to confmn CR (see 
Section 7. 7) 
For subjects with PD, a PBMC sample should be collected at time of progression and 
prior to staiiing subsequent anticancer therapy 
Locally evaluated % blasts from the bone mairnw evaluation and if available local MRD will be 
entered to the CRF. 
Overall response will be assessed by the investigator per Appendix 1. If bone maiTow blasts ai·e 
5% and circulating blasts ai·e 
1 %, then additional studies ( eg, flow cytometiy) should be 
perfo1med to quantify the blasts. 
Bone maiTow aspirate and biopsy samples will be processed and submitted to the centi·al 
laborato1y as outlined in the cenu-al laborato1y manual. Refer to the laborato1y manual for 
collection, processing and shipment requirements; note some sainples, eg, MRD, must be 
shipped on the saine day of collection. Below is an overview of the sample types that will be 
required. 
Sainples from bone maiTow aspirate may include: 
• 
MRD assessment 
• 
Stained slide smeai·s 
-
The same slides used to evaluate ALL disease status ( eg, % blasts) locally will be 
submitted to the centi·al laborato1y and will then be returned back to the investigative site 
after the review is completed. If the saine slides used to diagnose ALL cannot be 
submitted to the centi·al laborato1y per institutional policy, then slides from the saine 
procedure should be submitted. See centi·al laborato1y manual for details. 
• 
Bone maiTow mononuclear cells 
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Samples from bone marrow biopsy may include:

Touch prep slide

Core biopsy in formalin, formalin-fixed paraffin embedded block, or unstained slides
The corresponding pathology report should be submitted to the central laboratory along with the 
archival and on-study bone marrow samples. 
7.9.2.
Imaging Requirements (Only Applies to Subjects with Known Non-CNS 
Extramedullary Disease at Baseline)

Extramedullary disease will be assessed prior to baseline with an imaging modality 
appropriate for the anatomical site and clinical scenario (eg, MRI for CNS lesion, ultrasound 
for testicular lesion, CT for intra-abdominal or thoracic lesion).  
For all subjects with known non-CNS extramedullary disease, images must be taken 
within 28 days before conditioning chemotherapy.  In addition, for subjects receiving 
bridging chemotherapy, images must be taken after bridging chemotherapy has 
completed. 

Following KTE-X19 infusion, the first on study images will occur at the time of first 
presumed response (ie, bone marrow blasts ≤ 5%)

Subsequent images will continue as per the SOA through Month 24 or disease progression, 
whichever occurs first.  If the subject’s disease has not progressed by Month 24, then images 
will be performed per standard of care until disease progression.

All on-study assessments of extramedullary disease detected through imaging should be 
made with the same imaging modality and of the same anatomical locations as imaged at 
baseline.  

Response is evaluated by the investigator (Appendix 1).  

For all subjects, images should be performed per standard of care anytime the subject 
presents with symptoms suggestive of disease progression even if it is off schedule as per the 
SOA. 

Images will be submitted to a central imaging vendor; central imaging vendor manual to be 
provided separately.
7.10.
Biomarkers
Biomarker analysis will be performed on blood and bone marrow derived tumor samples to 
evaluate predictive and pharmacodynamic markers for KTE-X19.  Prognostic markers specific 
for B-ALL and related to the tumor immune environment may also be evaluated. 


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-103 
Amendment 7 
The presence, expansion, persistence, and immunophenotype of transduced anti-CD 19 CAR T 
cells will be monitored in the blood and bone maiTow by flow cytometiy . Expansion and 
persistence in peripheral blood will also be monitored by a CD 19 CAR specific droplet digital 
chain reaction assay (ddPCR). 
Levels of sernm cytokines and chemokines will be evaluated in the blood and CSF. The analysis 
of cytokines and chemokines in the CSF will be perfo1med at baseline and post-anti-CD19 CAR 
T cell infusion in subjects who present with first onset of~ grade 2 nemologic events. An 
additional sample for sernm cytokine and chemokine analysis should be drawn at first onset and 
first reoccmTence of any > grade 2 CRS (per Lee 2014 criteria; Table 15) if not ah-eady collected 
on that day. The following cytokines may be included in the panel: pro-inflammato1y and 
immune modulating cytokines IL-6, TNFa, IL-8, IL-1, IL-2, GM-CSF, IL-15, IL-17a, IFNy, 
IL-12p40/p70; immune effector molecules Granzyme A, B, Perforin, sFasL; coITelates of acute 
phase response C-reactive protein (CRP), SAA and Chemokines MIP-la, MIP-3a, IP-10, 
Eotaxin, MCP-4. 
Cerebrospinal fluid (CSF) as well as any additional subject samples (eg, plemal fluid) may be 
collected from subjects who develop nemologic events or CRS to enable evaluation of 
inflammato1y cytokines and chemokine levels. As applicable lymphocyte populations residing in 
the CSF or other additional subject samples may also be analyzed for the pm-pose of 
understanding the safety profile of KTE-X19. 
As KTE-X19 comprises retroviral vector ti·ansduced T cells, the presence of RCR in the blood of 
ti·eated subjects will be monitored. Replication-competent reti·ovirns testing will occm at 
baseline, Month 3, Month 6, and Month 12. Thereafter, samples will be collected yearly and held 
for up to 15 yeai·s. 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 15 yeai·s or as clinically indicated. 
Baseline leukapheresis and final KTE-X19 samples will be banked and may be analyzed by 
immunopheno 
in , uantitative ol 
erase chain reaction 
PCR and/or ene ex ression 
rofilin . 
A pre-ti·eatment bone maiTow aspirate and biopsy will be collected for centi·al pathology review, 
establishment of baseline protein and molecular mai·kers for subsequent MRD assessment and 
evaluation of prognostic markers specific for B-ALL and also the tumor immune 
environment. Additional anal sis ma include CD 19 ex ression 
ene ex ression rofilin and 
anal sis of DNA alterations. 
Monitoring of MRD to dete1mine presence of residual leukemic blasts will be perfo1med on bone 
manow aspirates. Standai·d assessment ofMRD utilizing multicolor flow cytometiy or qPCR to 
detect residual cancerous cells with a sensitivity of 10·4, will be accompanied by a more sensitive 
analysis utilizing next generation sequencing with a sensitivity of 10·6. The latter detects clonal 
B-cell specific sequences that are shai·ed across the malignant cell population. Given that 
clinical coITelates of MRD status in B-ALL are based on a threshold of 10·4, and clinical 
ificance of identi ing blasts at the 10·6 level is uncertain, the higher sensitivity analysis is 
only and will not be used to derive the endpoint ofMRD rate. 
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Protocol KTE-Cl9-103 
Amendment 7 
For subjects who withdraw consent, any samples that were not requested to be returned or 
destroyed will remain with the sponsor and any data that may be generated will be entered in the 
study database. 
7.11. 
Procedures by Study Period 
Investigative sites will maintain a log of all screened subjects who were reviewed and evaluated 
for study paiiicipation. Infonnation collected on the screening log should include limited 
infonnation such as the date of screening, date the subject was enrolled or the reason for why the 
subject failed screening. 
7.11.1. 
Screening 
The screening period begins on the date the subject signs the IRB/IEC approved ICF and 
continues through enrollment. Info1med consent must be obtained before completion of any 
study specific procedures. Procedures that ai·e part of SOC are not considered study specific 
procedures and may be perfo1med prior to obtaining consent and used to confnm eligibility. 
Confinnation of this data must occur within the time allowance as outlined below and in the 
SOA. 
After written infonned consent has been obtained, subjects will be screened to confnm study 
eligibility and paiiicipation. Only subjects who meet the eligibility criteria listed in Section 5 
and who commence leukapheresis will be enrolled into the study. If at any time prior to 
enrollment the subject fails to meet the eligibility criteria, the subject should be designated as a 
screen failure on the subject screening log with the reasons for failing screening. 
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The following assessments/procedures are to be completed during the screening period at the 
time points outlined in the SOA:

Medical history (see Section 7.3)

Physical examination including height and weight (see Section 7.4)

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

ECOG performance status 

EQ-5D (Phase 2 subjects only; see Section 7.4)

Neurological assessment (see Section 7.5)

ECG (see Section 7.6)

Left ventricular ejection fraction (LVEF) and pericardial effusion assessment (ECHO) (see 
Section 7.6)

Labs (see Section 7.8)
β-HCG pregnancy test (serum or urine) on all women of child-bearing potential
Chemistry panel
CBC with differential
Peripheral blood
CD19 immunophenotyping on peripheral blood or bone marrow aspirate
Lumbar puncture for collection of CSF (see Section 7.7)
For EU sites, viral serologic tests (eg, HIV, hepatitis B, hepatitis C) will be carried out 
per institution guidelines and EU regulations. This may be done within the 30 days prior 
to leukapheresis and/or on the day of leukapheresis.

CSF prophylaxis if indicated (see Section 6.4)

Chest x-ray (not required if other imaging modalities are used for baseline assessment of 
chest)

Disease assessment (see Section 7.7 and Section 7.9)


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
Screening bone marrow evaluation:
If available, archival formalin-fixed paraffin embedded (FFPE) bone marrow block 
and/or slides used for the original diagnosis of ALL will be submitted to the central 
laboratory  
A bone marrow aspirate and biopsy is required at screening and will be performed after 
the last dose of systemic chemotherapy and within approximately 14 days before 
enrollment to establish baseline disease.  
■
If there is a delay between when the screening bone marrow is performed and the 
apheresis, contact the Kite Medical Monitor for guidance on whether or not bone 
marrow evaluation needs to be repeated.  If a fresh bone marrow aspirate and biopsy 
was recently collected and properly stored prior to consent, then contact the Kite 
Medical Monitor to confirm if this sample is adequate for screening.    

Serious Adverse Event reporting (refer to Section 9)

Concomitant medications documentation and previous cancer treatment history (see 
Section 6.7)
7.11.2.
Rescreening
Subjects who are unable to complete or fail to meet the eligibility criteria during the 28-day 
screening period will be allowed to rescreen.  Subjects will retain the same subject indentifcation 
number assigned at the original screening.  If rescreening occurs within 28 days of the signing of 
the original informed consent, the assessment or procedure that initially resulted in the subject 
failing screening will be performed, including any other procedures that fell outside of the 
designated screening window (ie, lab assessments); all other initial screening 
procedures/assessments do not need to be repeated.
7.11.3.
Enrollment/Leukapheresis
Before leukapheresis commences, the following criteria must be met:

In general, all eligibility criteria confirmed during screening must not be known to be 
violated prior to leukapheresis.  Additionally, the investigator must review and confirm that 
the last CBC with differential and chemistry panel drawn prior to the start of leukapheresis 
must meet the eligibility criteria detailed in Inclusion criterion 105.  If any screening 
assessments or procedures are repeated between screening and the start of leukapheresis and 
results are outside the eligibility criteria (Section 5), contact the Kite medical monitor before 
proceeding with leukapheresis.  

Subjects must have no evidence of clinically significant infection prior to leukapheresis.  
Should a subject have clinically significant infection immediately prior to leukapheresis, cell 
collection must be delayed until the event resolves.  


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
If leukapheresis is delayed beyond 5 days, a CBC with differential and chemistry panel must 
be repeated.  

If WBC collected at time of leukapheresis is ≥ 50,000 cells/µL a contact must be made to the 
Kite Medical Monitor before proceeding with leukapheresis.

Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive drugs must be avoided for 
7 days prior to leukapheresis (see Section 6.8).
Once a subject commences leukapheresis, the subject will be considered enrolled into the study.   
The following procedures/requirements will occur on the leukapheresis collection day 
(enrollment) and as outlined in the SOA:

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

Weight (weight must be collected on the day of leukapheresis)

Labs (to be drawn prior to leukapheresis either on the day  of or the day before 
leukapheresis) (see Section 7.8)
Chemistry Panel
C-reactive protein; if CRP is ≥ 100 mg/L, contact the Kite Medical Monitor before 
proceeding with Conditioning chemotherapy
CD3 count 
CBC with differential 
Anti-KTE-X19 antibody
Blood draw for PBMCs and cytokine levels

Leukapheresis (see Section 6.2)

Adverse/Serious Adverse Event reporting (refer to Section 9) 

Concomitant medications documentation (see Section 6.7)
Vitals, lab draws, adverse/serious adverse event reporting and concomitant medications 
documentation may be performed the day before leukapheresis, unless otherwise specified.


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Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
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14 December 2021
7.11.4.
Bridging Chemotherapy Period
If prescribed, bridging chemotherapy will be administered after leukapheresis and completed at 
least 7 days or 5 half-lives, whichever is shorter, prior to initiating conditioning chemotherapy 
(see Section 6.3).  
The following procedures will be performed:

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

Labs (to be drawn prior to chemotherapy) (see Section 7.8)
Chemistry Panel 
CBC with differential

Bridging chemotherapy (see Section 6.3)

Adverse/Serious Adverse Event reporting (refer to Section 9) 

Concomitant medications documentation (see Section 6.7)
Note:  As appropriate, vitals and labs should be repeated each day bridging chemotherapy is 
administered.
7.11.5.
CSF Prophylaxis Period 
Intrathecal chemotherapy for CSF Prophylaxis will be administered any time during screening 
through 7 days prior to KTE-X19 infusion (see Section 6.4).  
The following procedures will be performed:

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

Labs (to be drawn prior to chemotherapy) (see Section 7.8)
Chemistry Panel 
CBC with differential
Lumbar puncture for collection of CSF (see Section 7.7)

Intrathecal chemotherapy (see Section 6.4)

Adverse/Serious Adverse Event reporting (refer to Section 9)  

Concomitant medications documentation (see Section 6.7)
Note: As appropriate, vitals and labs should be repeated each day CSF prophylaxis is 
administered.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 51
14 December 2021
7.11.6.
Conditioning Chemotherapy and KTE-X19 Infusion
Administration of KTE-X19 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 (elevated C-reactive 
protein [CRP]) are diagnoses of exclusion that require a documented workup to establish.  
Conditioning chemotherapy and KTE-X19 infusion should only be initiated after it is reasonably 
assured that cell infusion can safely proceed.  
The investigational medicinal product (KTE-X19) must be available before initiation of 
conditioning chemotherapy.
Refer to Section 7.11.7.5 for Requirements to Work-up Potential Infectious and/or Inflammatory 
States.
7.11.6.1.
Conditioning Chemotherapy Period
7.11.6.1.1.
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 7.11.7.5 must be performed to determine the potential cause if there 
is no identified source of infection.

Temperature > 38ºC within 72 hours before conditioning chemotherapy

CRP > 100 mg/L any time between enrolment to start of conditioning chemotherapy

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 segments/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 HEENT, cardiac, vascular, respiratory, 
gastrointestinal, integumentary, and neurological systems must not reveal evidence of 
infection/inflammation. 

The subject must not have received systemic anti-microbials for the treatment of a known or 
suspected infection within 48 hours before conditioning chemotherapy (prophylactic use of 
anti-microbials is allowed).  


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 52
14 December 2021

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 conditioning chemotherapy.
7.11.6.2.
Conditioning Chemotherapy Administration (Day -4 Through Day -2 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 –4.  
Subjects will initiate conditioning chemotherapy with cyclophosphamide and fludarabine 
beginning on Day –4 and through Day –2, with 1 rest day (Day -1) before receiving KTE-X19.  
The 3-day conditioning chemotherapy regimen will be administered in an outpatient setting.
Conditioning chemotherapy (fludarabine and cyclophosphamide) will be supplied by the 
investigative site unless otherwise noted and should be administered per institutional guidelines.  
Refer to the current product label for guidance on packaging, storage, preparation, administration 
and toxicity management associated with the administration of chemotherapy agents.
Before conditioning chemotherapy commences, the criteria outlined in Section 7.11.6.1 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:

Subjects should receive IV hydration with conditioning chemotherapy per institutional 
guidelines or investigator discretion; recommendations for IV hydration are listed below:

IV pre-hydration starting 90 minutes prior to fludarabine and continuing for at least 8 hours 
after with 0.45% sodium chloride and 5% dextrose (or other composition appropriate for the 
clinical situation) at a rate of at least 90 mL/m2/hour.  Hydration may be temporarily 
interrupted to give fludarabine or cyclophosphamide but should continue until at least 
8 hours after the cyclophosphamide dose has been completed.

Fludarabine 25 mg/m2/day IV in 50 mL of 0.9% sodium chloride over 30 minutes on Day -4, 
Day -3, Day -2 followed by: 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 53
14 December 2021

Cyclophosphamide at a dose of 900 mg/m2/day IV over 60 minutes on Day -2 only 

Add mesna per institutional guidelines 

Subjects should be instructed to drink plenty of liquids during and for 24 hours following the 
chemotherapy (total fluids approximately 1.5 L/m2/24 hours IV + PO).  In general, subjects 
should be kept well hydrated but closely monitored to prevent fluid overload. 

Subjects should be instructed to drink plenty of liquids during and for 24 hours following the 
chemotherapy (approximately 2 liters/24 hours) if no contraindications.  In general subjects 
should be kept well hydrated but closely monitored to prevent fluid overload. 
7.11.6.3.
Conditioning Chemotherapy Procedures
The following procedures will be completed during Day -4 to Day -2. Day -1 is a rest day. 

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

ECOG performance status

Labs (to be drawn prior to chemotherapy) (see Section 7.8)
β-HCG pregnancy test (serum or urine) on all women of child-bearing potential
Chemistry Panel 
CBC with differential
■
Note:  If subject did not have bridging therapy and hence bone marrow is not 
collected between the end of bridging chemotherapy and start of Conditioning 
chemotherapy, then sites must assess peripheral blasts counts during this time period 
(eg, at Day -4). 
Blood draw for PBMCs and cytokine levels

Bone marrow evaluation (see Section 7.9.1)
In subjects who receive bridging chemotherapy, an additional bone marrow sample is 
required between the end of bridging chemotherapy and Day -4.  If bridging 
chemotherapy is not administered, then the additional bone marrow sample is not 
required.   

Conditioning chemotherapy (Fludarabine and cyclophosphamide) administration (see 
Section 6.5)

Adverse/Serious Adverse Event reporting (refer to Section 9)  

Concomitant medications documentation (see Section 6.7)


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 54
14 December 2021
7.11.7.
Investigational Product Treatment Period
7.11.7.1.
Pre-KTE-X19 Infusion Criteria
If any of the following criteria are met prior to the initiation of KTE-X19, then the work-up listed 
in Section 7.11.7.5 must be performed to determine the potential cause if there is no identified 
source of infection.  

Temperature > 38°C within 72 hours of KTE-X19 infusion

CRP > 100 mg/L any time between enrollment to start of KTE-X19 infusion

WBC count or WBC differential concerning for infectious process between enrollment to 
start of KTE-X19infusion (eg, WBC > 20,000, rapidly increasing WBC, or differential with 
high percentage of segments/bands)
Additionally:

All eligibility criteria of the protocol must be met.  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, and cardiac, vascular, respiratory, 
gastrointestinal, integumentary, and neurological systems must not reveal evidence of 
infection/inflammation. 

The subject must not have received systemic anti-microbials for the treatment of a known or 
suspected infection within 48 hours before KTE-X19 (prophylactic use of anti-microbials 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.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 55
14 December 2021
If the KTE-X19 infusion is delayed > 2 weeks, protocol guidelines should be followed regarding 
the need for repeat conditioning chemotherapy. 
7.11.7.2.
Hospitalization for KTE-X19 Infusion
Subjects will be hospitalized to receive infusion of KTE-X19 followed by a minimum 7 day 
observation period unless otherwise required by country regulatory agencies (refer to Appendix 3 
for details). 
Subjects will remain in the hospital through day 7 post infusion of KTE-X19.  Subjects should 
not be discharged from the hospital until all KTE-X19-related non-hematological toxicities 
return to grade ≤ 1 or return to baseline.  Subjects may be discharged with non-critical and 
clinically stable or slowly improving toxicities (eg, renal insufficiency) even if > grade 1, if 
deemed appropriate by the investigator.  Subjects should remain hospitalized for ongoing 
KTE-X19-related fever, hypotension, hypoxia, or ongoing central neurological toxicity 
> grade 1, or if deemed necessary by the treating investigator. 
Given the possibility that a subject could develop CRS or neurologic events in the outpatient 
setting after discharge, subjects and their family members/caregivers should be educated on 
potential symptoms of these syndromes such as fever, dyspnea, confusion, aphasia, dysphasia, 
somnolence, encephalopathy, ataxia, or tremor.  If subjects develop these symptoms, they should 
be instructed to immediately contact the principal investigator or seek immediate medical 
attention. 
See Section 6.8 for excluded medications prior to and after KTE-X19.
7.11.7.3.
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 Kite 
medical monitor

Acetaminophen 650 mg PO or equivalent

Diphenhydramine 12.5 mg administered either orally or via IV or equivalent
7.11.7.4.
KTE-X19 Infusion (Day 0)
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 
the IPM.  It is recommended that vital signs are recorded before KTE-X19 infusion and then 
routinely as clinically indicated (eg, fever ≥ 38.3°C). 
The IPM must be reviewed prior to administration of KTE-X19. 
Research sites should follow institutional guidelines for the infusion of cell products.


KTE-X19 
Kite Pha1m a, Inc. 
Protocol KTE-Cl9-103 
Amendment 7 
During this period, the following procedures will be completed at the time points outlined in the 
SOA: 
• 
Vital signs including blood pressure, heali rate, oxygen saturation, and temperature eve1y 
Q4-6 hours during hospitalization (see Section 7.4 for vital sign requirements during the 
initial hospitalization) 
• 
ECOG perfo1mance status 
• 
EQ-5D (Phase 2 subjects only; see Section 7.4) 
• 
Neurological assessment (see Section 7.5) 
• 
Labs (before KTE-X19 infusion) (see Section 7.8) 
-
Cheinistiy Panel 
-
CBC with differential 
-
Blood draw for PBMCs and cytokine levels (See SOA for frequency) 
-
Recommended: Monitoring of CRP, feITitin, and LDH (only ifLDH is elevated at 
baseline) levels may assist with the diagnosis and define the clinical course in regards to 
CRS/neurologic events. It is, therefore, recommended that CRP, feITitin, and LDH (if 
elevated at baseline) be monitored daily staiting at Day O and continuing through 
hospitalization. In addition, lactate should be monitored as clinically indicated. 
• 
Lumbar puncture for subjects with first onset grade 
2 neurologic symptoms should be 
completed for examination of CSF (see Section 7.7) 
• 
As applicable, an additional cytokine sample should be drawn at the first onset and first 
reoccuITence of any~ grade 2 CRS (per Lee 2014 criteria; Table 15) if not ah-eady collected 
on that day 
• 
Bone maITow evaluation (see Section 7.9) 
• 
KTE-X 19 pre-medications ( see Section 7 .11. 7. 3) 
• 
Infusion ofKTE-X19 
• 
Adverse/Serious Adverse Event reporting (refer to Section 9 for safety reporting guidelines) 
• 
Concoinitant medications documentation (see Section 6.7) 
CONFIDENTIAL 
Page 56 
14 December 2021 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 57
14 December 2021
7.11.7.5.
Requirements to Work-Up Potential Infectious and/or Inflammatory States Prior 
to KTE-X19 Infusion
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 anti-microbials if clinically 
feasible): 
Blood cultures (aerobic and anaerobic x2 bottles each) and UA and urine culture.   
Deep/induced sputum culture if clinically indicated.
All indwelling lines, such as central venous catheters, should be examined for any signs 
of infection, and additional cultures should be drawn from the line.
Nasopharyngeal-throat (NPT) swab or equivalent assay for viral infection such as 
influenza A/B (including H1N1), parainfluenza 1/2/3, adenovirus, respiratory syncytial 
virus, coronavirus, metapneumovirus
Collection of fungal cultures and markers as appropriate (eg, galactomannan, fungitell)
Collection of appropriate serum viral studies (eg, cytomegalovirus [CMV])

If a central nervous system process is suspected, appropriate brain imaging and subsequent 
lumbar puncture with cytology, culture, Gram stain, and viral PCR should be performed.  

Any additional sign or symptom-directed investigation should be performed as clinically 
indicated.
Prior to proceeding with conditioning chemotherapy and/or KTE-X19 infusion, the above 
workup must not suggest the presence of an active infection, and all requirements for 
conditioning chemotherapy and/or KTE-X19 infusion must be satisfied.  If the KTE-X19 
infusion is delayed > 2 weeks following conditioning chemotherapy, protocol guidelines should 
be followed regarding the need for repeat conditioning chemotherapy. 

If the above workup was triggered due to CRP > 100 mg/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.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 58
14 December 2021
7.11.8.
Post-treatment Assessment Period
After completing KTE-X19 infusion and discharged from the hospital, all subjects will be 
followed in the post treatment assessment period. Counting from day 0 (KTE-X19 infusion), 
subjects will return to the clinic at the following intervals.

Day 14 (± 2 days)

Day 28 (+ 3 days)

Week 8 (± 1 week)

Month 3 (± 2 weeks)
Subject will allow key sponsor contacts to continue to access medical records so that information 
related to subjects health condition and initial treatment response may be obtained.  
The following procedures will be completed for subjects as outlined in the SOA:

Physical exam

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

EQ-5D (Phase 2 subjects only; see Section 7.4)

Neurological assessment (see Section 7.5)

Labs (see Section 7.8)
β-HCG pregnancy test (serum or urine) on all women of child-bearing potential
Chemistry Panel 
CBC with differential 
Anti-KTE-X19 antibodies
Blood draw for PBMCs and cytokine levels 

Lumbar puncture for subjects with first onset grade ≥ 2 neurologic symptoms should be 
completed for examination of CSF (see Section 7.7)

As applicable, an additional cytokine sample should be drawn at the first onset and first 
reoccurrence of any ≥ grade 2 CRS (per Lee 2014 criteria; Table 15) if not already collected 
on that day  

Disease Assessment (see Section 7.7 and Section 7.9)


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 59
14 December 2021

Adverse/Serious Adverse Event reporting (refer to Section 9 )

Concomitant medications documentation (see Section 6.7)
Following the initial hospitalization for the KTE-X19 infusion, if the subject is hospitalized with 
any KTE-X19 related adverse event, 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
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 child-bearing potential

Proceed to the long term follow-up period (see Section 7.11.9 for details).
7.11.9.
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.  Subjects will begin the long term follow-up period after they have 
completed the Month 3 visit of the post-treatment assessment period (whether they responded to 
treatment or went straight to the month 3 visit due to disease progression). After completion of 
the Month 24 visit, subjects who received an infusion of KTE-X19 will be provided the 
opportunity to transition to a separate LTFU study, KT-US-982-5968 (refer to section 3.5.3).

Every 3 months (± 2 weeks) through Month 18

Every 6 months (± 1 month) between Month 24 - Month 60

Beginning with year 6, Month 72 (± 3 months), subjects will return to the clinic 1 time 
annually up to 15 years after the last subject receives their KTE-X19 infusion.  
The following procedures will be completed for subjects who are enrolled and receive KTE-X19, 
at the time points outlined in the SOA:

Physical exam 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 60
14 December 2021

EQ-5D (Phase 2 subjects only; see Section 7.4)

Disease assessment (see Section 7.7 and Section 7.9) 
Note:  Disease assessment is performed per the SOA through month 24 or until disease 
progression, whichever occurs first.  If the subject’s disease has not progressed by 
Month 24, then after Month 24 disease assessments will be performed per standard of 
care.

Survival Status – subjects may be contacted by telephone to confirm survival status 

Labs (see Section 7.8)
CBC with differential 
Anti-KTE-X19 antibodies 
■
For serum samples that demonstrate increased anti-KTE-X19 antibodies at the month 
3 visit over baseline values, attempts should be made to obtain and test additional 
serum samples approximately every 3 months until the antibody levels return to 
baseline (or becomes negative) or up to 1 year from the completion of treatment, 
whichever occurs first
Blood draw for PBMCs 
■
A PBMC sample should be collected at time of progression and prior to starting 
subsequent anticancer therapy 

Targeted Adverse/Serious Adverse Event reporting  (refer to Section 9 for safety reporting 
guidelines)

Targeted Concomitant medication documentation (see Section 6.7)

Subsequent therapy for the treatment of ALL (see Section 6.8)
Subjects who undergo an allogeneic SCT will continue to be followed in the LTFU period and 
undergo the following assessments at the timepoints outlined in the SOA:

Disease status

Survival status

Serious Adverse Event reporting (see Section 9.4)

Concomitant medications documentation (see Section 6.7) 

Subsequent therapy for ALL (see Section 6.9)


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 61
14 December 2021

Blood draw for:
PBMCs
If applicable anti-KTE-X19 antibodies (see Section 7.11.9)  
Subjects who receive infusion of KTE-X19, but who experience disease progression, will be 
followed in the LTFU period and undergo the following assessments at the timepoints outlined in 
the SOA:

Survival status

Serious Adverse Event reporting (see Section 9)

Concomitant medications documentation (see Section 6.7)

Subsequent therapy for ALL (see Section 6.9)

Blood draw for:
PBMC’s
 If applicable anti-KTE-X19 antibodies (see Section 7.11.9).
Subjects who are enrolled/leukapheresed, but did not receive KTE-X19 treatment, will be 
followed and will undergo the following assessments at the timepoints outlined in the SOA only 
until the end of this study (refer to Section 3.5.2):

Disease assessment per standard of care 

Survival status 

Subsequent therapy for the treatment of ALL (see Section 6.9) 

Adverse/Serious Adverse Event reporting (refer to Section 9 )

Concurrent therapies (see Section 6.7)
Should the subject fail to return to the clinic for a scheduled protocol-specific visit, sites will 
need to make 2 attempts by a combination of telephone and mail to contact the subject.  Sites 
must document both attempts to contact the subject. If a subject does not respond within 1 month 
after the second contact the subject will be considered lost to follow-up and no additional contact 
will be required.


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
CONFIDENTIAL
Page 62
 14 December 2021
Table 4.
Schedule of Assessments 
Schedule of Assessments 
(1 of 2) Procedures
Screening 9
Enrollment / 
Leukapheresis
Conditioning 
Chemotherapy 
Period
IP 
Administration 
Period 11
Post Treatment Follow-up 10, 11
(each visit calculated from Day 0)
Visit Frequency
≤ 14 days 
before 
enrollment
≤ ~5 days 
after 
eligibility 
confirmation
Bridging 
Chemotherapy
CSF 
Prophylaxis
-4
-
3
-
2
-
1
0
1 – 7 13
Day 14
(± 2 
days)
Day 28
(+ 3 
days)
Week 
8
(± 1 
week)
Month 
3
(± 2 
weeks)
Medical history 
X
Physical exam
X
X
X
X
X
Vital signs 1
X 1
X 5
X 7
X 7
X
X
X
X 1
X 1
X
X
X
X
Weight
X
X 5
ECOG Performance Status
X
X
X
Neurological Assessment 8
X
X
X 8
X
X
EQ-5D (Phase 2 subjects only) 14
X
X
X
X
ECG
X9
LVEF and PE assessment by 
ECHO 
X9
Chest x-ray
X
Bone Marrow Evaluation 
(biopsy and aspirate) for 
Disease Assessment 2
X 2
X 
2
Opt. 
Day 7 Bx 
& A 2
X 2
X 2
X 2
Extramedullary Imaging 3
X 3
X 3
X 3
X 3
Overall Response Assessment 
(Appendix 1)
X
X
X
Leukapheresis 5
X
CSF Prophylaxis 6
X 6
Bridging Chemotherapy  6
X 6
Conditioning Chemotherapy 
(Fludarabine &  
Cyclophosphamide) 6
X
X
X


KTE-X19 
Kite Pha1ma, Inc. 
Protocol KTE-Cl9-103 
Amendment 7 
Conditioning 
IP 
Schedule of Assessments 
Enrollment / 
Chemotherapy 
Administration 
Post Treatment Follow-up 10, 11 
(1 of 2) Procedures 
Screening 9 
Leukapheresis 
Pe1iod 
Period 11 
(each visit calculated from Day 0) 
~-5 days 
Week 
Month 
14 days 
after 
Day 14 
Day28 
8 
3 
before 
eligibility 
Bridging 
CSF 
-
-
-
(± 2 
(+ 3 
(± 1 
(± 2 
Visit Frequency 
enrollment 
confu·mation 
Chemotherapy 
Prophylaxis 
-4 
3 
2 
1 
0 
1- 7 13 
days) 
days) 
week) 
weeks) 
KTE-Xl9 infusion IV 
x •2 
Pregnancy test (serum or urine 
X 
X 
X 
~-HCG) 
Chemistry panel & CBC with 
X 
xs 
x 1 
x 1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
differential 7 
CD3 count 
xs 
CD 19 inimunophenotyping 
X9 
C-Reactive Protein 
xs 
Lumbar Puncture for collection 
X4 
X4 
X4 
X4 
ofCSF4 
Anti-KTE-X19 antibody 
xs 
X 
X 
Peripheral blood 
x 1 
x 1 
Blood draw for PBMCs 11 
xs 
X 
Day? 
X 
X 
X 
X 
6 
Blood draw for cytokines 11 
xs 
X 
X 
Day3 
X 
X 
6 
and 7 
Adverse events/ Concomitant 
X 
-
medication 
-
Footnotes for Schedule of Assessments (1 of 2) 
1 
Vital signs: Includes blood pressure, heart rate, oxygen saturation, and temperature. Height will be collected at screening. Vitals will be monitored before and after the KTE-X19 
infusion and then routinely (every 4-6 hours) while hospitalized. If the subject has a fever (temperature 38.3oC or greater) at any time during hospitalization, vital signs will be 
monitored more frequently as clinically indicated. 
2 
Bone Marrow Evaluation (biopsy and aspirate) for Disease Assessment (Section 7.9): For screening bone marrow evaluation see section 7.9.1. A bone marrow aspirate will be required 
at all timepoints per the SOA table above (Subjects that receive an SCT, bone marrow evaluations are not required for the first 100 days post SCT). In addition to the bone marrow 
aspirate, a bone marrow biopsy is required at Screening, Day -4 and Day 28. The Day -4 bone marrow biopsy is only required for subjects receiving bridging chemotherapy. A bone 
marrow biopsy at all other timepoints is recommended and should be performed if standard of care. Anytime the bone marrow aspirate is a dry tap, then a bone marrow biopsy is 
required. Disease status will be evaluated per institutional ractices. A ortion of the 
irate collected will be submitted to the central lab on the da of collection and anal ed for 
MRD; see the central laborato 
manual for details. 
CONFIDENTIAL 
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3
Extramedullary Imaging (Section 7.9.2):  For subjects with known baseline extramedullary disease detected through imaging, baseline images appropriate for the anatomical location 
and clinical scenario will be performed.  For subjects receiving bridging chemotherapy, images will be performed after bridging chemotherapy and before conditioning chemotherapy.  
For subjects not receiving bridging chemotherapy, images will be performed within 28 days before conditioning chemotherapy.  On study images will be performed with the same 
imaging modality and anatomical location as imaged at baseline.  Following KTE-X19 infusion, the first on study images will occur at the first occurrence of leukemia remission based 
on the bone marrow evaluation.  Subsequent images will continue as per the SOA through Month 24 or disease progression, whichever occurs first.  If the subject’s disease has not 
progressed by Month 24, then images will be performed per standard of care until disease progression.  For subjects with or without extramedullary disease, images should be performed 
per standard of care anytime the subject presents with symptoms suggestive of disease progression.
4
Lumbar Puncture (Section 7.7): CSF samples will be analyzed locally for disease assessment and centrally for disease assessment and toxicity evaluation at the following timepoints:  1) 
Baseline – a CSF result obtained within 30 days before enrollment will be acceptable eligibility determination, 2) at the time of CSF prophylaxis, 3) for subjects with baseline CNS-2 
disease, a CSF sample is required at the time of first presumed response  based on bone marrow (bone marrow <5%), 4) first onset of grade 2 or greater neurological symptoms or as 
medically indicated 5) for subjects with a CR, collection and analysis of CSF is required to confirm CR and 6) per institutional standard of care. Should a subject have an Ommaya 
reservoir and there is no evidence of blockage of CSF flow from the spinal canal, withdrawal of the CSF sample though the reservoir is acceptable. CSF samples (ie, collected on or 
after informed consent) will be submitted to the central laboratory.
5
Leukapheresis (Sections 6.2 and 7.11.3): All leukapheresis criteria must be met before leukapheresis commences.  Vitals, weight, and laboratory sample draws may be performed the s 
day of or before  leukapheresis, except weight must be collected on day of leukapheresis.  All laboratory samples should be drawn before the leukapheresis procedure.  For EU sites, 
viral serologic tests (eg, HIV, Hep B, Hep C) will be carried out per institution guidelines and EU regulations. This may be done within the 30 days prior to leukapheresis and/or on the 
day of leukapheresis (see Section 7.11.1).
6
Chemotherapies:  Bridging chemotherapy (Section 6.3) will be administered after leukapheresis and completed at least 7 days or 5 half-lives, whichever is shorter, prior to initiating 
conditioning chemotherapy.  CSF prophylaxis (Section 6.4) will be administered any time during screening through 7 days before the KTE-X19 infusion.  Subjects who are enrolled 
with CNS-2 disease at baseline must receive CSF prophylaxis after leukapheresis and at least 7 days prior to KTE-X19, unless otherwise approved by the Kite Medical Monitor. 
Multiple doses of CSF prophylaxis can be given per investigator discretion in accordance with institutional guidelines, but at least 7 days must pass between the last dose of CSF 
prophylaxis and KTE-X19. Should a subject have an Ommaya reservoir and there is no evidence of blockage of CSF flow from the spinal canal, administration of CSF prophylaxis 
through the reservoir is acceptable.  Conditioning chemotherapy (Section 6.5) consisting of fludarabine on Day -4, -3, -2 prior to KTE-X19 and cyclophosphamide on Day -2 prior to 
KTE-X19 will be administered.
7
Vitals, Chem panel, and CBC: collected each day prior to CSF prophylaxis and bridging chemotherapy (see Section 7.11.4 and 7.11.5).  CBC 5-part preferred, but 3-part will be 
acceptable.  Peripheral blood:  Peripheral blood will be collected at screening, and if the subject did not have bridging therapy than peripheral blood will be collected during day -4 and 
submitted to the central lab.
8
Neurological assessment: 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.  
9
Screening procedures (Section 7.11.1):  Procedures should be performed within 14 days of enrollment (unless otherwise specified).  ECG: must be performed within 30 days prior to 
enrollment; ECHO: If the last chemotherapy regimen the subject received is not considered cardiotoxic, then an ECHO performed within 28 days prior to signing the consent may be 
used for eligibility.  If the last chemotherapy regimen the subject received is considered cardiotoxic, then an ECHO performed following the subjects last chemotherapy treatment and 
within 28 days prior to signing the consent may be used for confirmation of eligibility.  CD19: Local CD19 immunophenotyping will be performed at screening on peripheral blood or 
bone marrow aspirate.  Surface CD19 expression should be measured by flow cytometry; IHC analysis is allowed if the bone marrow aspirate is a dry tap, inadequate or there were 
insufficient circulating blasts for flow cytometry.  Procedures that are part of SOC are not considered study specific procedures and may be performed prior to obtaining consent and 
used to confirm eligibility provided they are performed within the time allowance as outlined in the SOA.
10
If the subject progressions before Month 3:  Refer to section 7.11.8 for the procedures that are to be completed.
11
Following the initial hospitalization for the KTE-X19 infusion (Section 7.11.8):  Following the initial hospitalization for the KTE-X19 infusion, if the subject is hospitalized with any 
KTE-X19 related adverse event, a blood sample for PBMCs and cytokines will be collected on day of admission, then weekly, and on day of discharge.  A PBMC sample should be 
collected at time of progression and prior to starting subsequent anticancer therapy. As applicable, an additional cytokine sample should be drawn at the first onset and first reoccurrence 
of any > grade 2 CRS (per Lee 2014 criteria) if not already collected on that day.
12
KTE-X19 pre-medications:  Subjects will receive acetaminophen and diphenhydramine (equivalent) approximately 1 hour prior to KTE-X19 (see Section 7.11.7.3).
13
Please refer to Appendix 3 for requirements by country regulatory agencies
14
EQ-5D:  The EQ-5D will be completed prior to other study related procedures or assessments.


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Protocol KTE-C19-103 
Amendment 7
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Schedule of Assessments 
(2 of 2) Procedures
Long Term Follow-up Period 8, 9
(Each visit calculated from Day 0)
Visit Frequency
Month 
6
Month 
9
Month 
12
Month 
15
Month 
18
Month 
24
Month 
30
Month 
36
Month 
42
Month 
48
Month 
54
Month 
60
Month 72 and 
Annually Up 
to 15 Years
Physical exam
X
X
X
X
X
X
EQ-5D (Phase 2 subjects only)
X
X
X
X
X
X
Bone Marrow Evaluation (biopsy and 
aspirate) for Disease assessment 1
X
X
X
X
X
X
Extramedullary Imaging 2
X 2
X 2
X 2
X 2
X 2
X 2
Overall Response Assessment 
(Appendix 1)
X
X
X
X
X
X
Survival Status 4, 7, 8
X
X
X
X
X
X
X
X
X
X
X
X
X
CBC with differential (5 part preferred, 3 
part acceptable)
X
X
X
X
X
X
Anti-KTE-X19 antibody 3, 8
Blood draw for PBMCs 8
X
X
X
X
X
X
X
X
X
X
Adverse Event Reporting 4
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medications Reporting 5
X
X
X
X
X
X
X
X
X
X
X
X
X
Subsequent therapy for ALL 6, 8 
X
X
X
X
X
X
X
X
X
X
X
X
X
1
Bone Marrow Evaluation (biopsy and aspirate) for Disease Assessment (Section 7.9.1): A bone marrow biopsy and aspirate will be performed per the SOA through Month 24 or until 
disease progression, whichever occurs first.  Disease status will be evaluated per institutional practices.  The slides used for the local evaluation of % blasts should be submitted to the 
central laboratory along with the corresponding pathology report.   If the subject’s disease has not progressed by Month 24, then after Month 24 bone marrow evaluation will be 
performed per SOC.
2
Extramedullary Imaging (Section 7.9.2): For subjects with baseline extramedullary disease:  Following KTE-X19 infusion, the first on study images will occur at the first occurrence of 
leukemia remission based on the bone marrow evaluation.  Subsequent images will continue as per the SOA through Month 24 or disease progression, whichever occurs first.  If the 
subject’s disease has not progressed by Month 24, then images will be performed per standard of care until disease progression.  For subjects with or without extramedullary disease, 
images should be performed per SOC anytime the subject presents with symptoms suggestive of disease progression.
3
Anti-KTE-X19: For antibody sample collection in long-term follow-up, refer to Section 7.11.9 for details.
4
AE/SAE reporting (Sections 9.2 and 9.4):   AEs: After 3 months, only targeted adverse events will be reported in the CRF through 24 months after KTE-X19 infusion or disease 
progression, whichever occurs first.  SAEs: After 3 months, only targeted serious adverse events (including targeted grade 5 serious adverse events) will be reported through 24 months 
after KTE-X19 infusion or disease progression, whichever occurs first, within 24 hours using the SAE Report Form and in the CRF.  Targeted adverse events include central 
neurological, hematological, infections, GVHD, autoimmune disorders, and secondary malignancies.  Subjects who receive an allogeneic SCT will only be followed for KTE-X19 
related serious adverse events.  Reporting of these SAEs will commence at the time the SCT preparative regimen commences through 24 months after KTE-X19 infusion or disease 
progression, whichever occurs first, within 24 hours using the SAE Report Form and in the CRF. In addition to the above SAE reporting requirements, anytime a KTE-X19 related 
serious adverse event occurs it will be reported within 24 hours using the SAE Report Form and in the CRF.  All deaths that occur from ICF through end of study will be reported in the CRF. 


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Protocol KTE-C19-103 
Amendment 7
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5
Concomitant medications reporting (Section 6.7):   After 3 months of follow-up, only targeted concomitant medications will be collected for 24 months after KTE-X19 infusion or 
disease progression, whichever occurs first.  Targeted concomitant medications include gammaglobulin, immunosuppressive drugs, anti-infective drugs, and vaccinations.
6
Subsequent therapy for ALL (Section 6.9):  Documentation of subsequent therapy for ALL will continue to be documented while the subject remains on study.  Subjects may be 
contacted by telephone. 
7
Survival Status (Section 7.11.9):  Subjects may be contacted by telephone to confirm survival status.
8
If the subject progresses in the LTFU phase (Section 7.11.9), the subject will be followed in the LTFU phase for survival status, subsequent therapy for ALL and have blood drawn for 
PBMC’s and if applicable anti-KTE-X19 antibodies.  A PBMC sample should be collected at the time of progression and prior to starting subsequent anticancer therapy.
9
After completion of at least 24 months of assessments in the KTE-C19-103 study, subjects who received an infusion of KTE-X19 will be provided an opportunity to transition to the 
LTFU study (KT-US-982-5968) after providing signed informed consent, to complete the remainder of the 15-year LTFU period. 


KTE-X19
Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
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8.
SUBJECT WITHDRAWAL
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution.
Subjects can decline to continue to receive study required treatment and/or other protocol 
required procedures at any time during the study but continue to participate in 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 investigational product, study treatment or other 
protocol required therapies and must discuss options for continued participation, completion of 
procedures and the associated data collection as outlined in the SOA.  The level of follow-up and 
method of communication should also be discussed between the research staff and the subject 
and documented in the source documents.
Withdraw of full consent for a study means that the subject does not wish to receive further 
protocol required therapy or undergo procedures and the subject does not wish to continue 
further study follow-up.  Subject data collected up to withdraw of consent will be retained and 
included in the analysis of the study, and where permitted by local regulations, publically 
available data (death records) can be included after withdrawal of consent.  The investigator is to 
discuss with the subject appropriate procedures for withdrawal from the study. 
As part of the study sites may be asked to conduct searches of public records, such as those 
establishing survival status, if available, to obtain survival data for any subject for whom the 
survival status is not known.  Sites may be also asked to also retrieve autopsy reports to confirm 
status of disease at the time of death. 
The investigator and/or sponsor can also decide to withdraw a subject from the investigational 
product and/or other protocol-required therapies, protocol procedures, or the study as a whole or 
at any time prior to study completion.
8.1.
Reasons for Removal from Treatment
Reasons for removal from protocol required investigational products or procedures include any 
of the following:

Adverse Event

Subject request

Product not available

Lost to Follow-up

Death

Decision by sponsor


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Kite Pharma, Inc.
Protocol KTE-C19-103 
Amendment 7
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8.2.
Reasons for Removal from Study
Reasons for removal of a subject from the study are as follows:

Subject withdrawal of consent from further follow-up

Investigator decision

Lost to follow-up 

Death


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Amendment 7
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9.
SAFETY REPORTING
9.1.
Adverse Events
An adverse event 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 adverse events observed by the investigator or reported by the 
subject are recorded in the subject’s medical record. 
The definition of adverse events 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 adverse event.
Interventions for pretreatment conditions (such as elective cosmetic surgery) or medical 
procedures that were planned before study participation are not considered adverse events.  
Hospitalization for study treatment infusions or precautionary measures per institutional policy 
are not considered adverse events.
The term “disease progression” or any relapse after a remission should not be reported as adverse 
events.  Death due to disease progression in the absence of signs and symptoms of underlying 
disease should be reported as the primary tumor type (eg, B-cell type acute leukemia). 
For situations when an adverse event or serious adverse event is due to the disease under 
investigation report the signs and symptoms.  Worsening of signs and symptoms of the 
malignancy under study should also be reported as adverse events in the appropriate section of 
the CRF. 
The investigators clinical judgment is used to determine whether a subject is to be removed from 
treatment due to an adverse event.  In the event a subject requests to withdraw from protocol 
required therapies or the study due to an adverse event, the subject should undergo the 
procedures outlined in the Month 3 visit of the SOA. 
9.1.1.
Diagnosis Versus Signs and Symptoms
For adverse events, a diagnosis (if known) rather than individual signs and symptoms should be 
recorded on the AE form.  The exception is for CRS where both the diagnosis and signs and 
symptoms will be captured on the CRF AE form.  For signs and symptoms of the underlying 
cancer, the signs and symptoms should be captured.  However, on the AE form, the investigator 
should state that these signs and symptoms are due to the underlying disease.


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Protocol KTE-C19-103 
Amendment 7
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9.1.2.
Abnormal Vital Sign Values
Not all vital sign abnormalities qualify as an adverse event.  A vital sign result must be reported 
as an adverse event if it is a change from baseline and meets any of the following criteria:

Accompanied by clinical symptoms

Results in a medical intervention or a change in concomitant therapy

Clinically significant in the investigator’s judgment
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 adverse event.  However, if a clinically significant vital sign abnormality is a sign 
of a disease or syndrome (eg, high blood pressure), only the diagnosis (ie, hypertension) should 
be recorded on the CRF.
9.1.3.
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 adverse event 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 in Table 5:


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Amendment 7
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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, bridging chemotherapy, 
conditioning chemotherapy) or until initiation of a 
new anti-cancer 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 SAEs.
Abbreviations:  GVHD, graft-versus-host-disease.
See Section 9.5 for reporting requirements.  
See Section 6.7 for targeted concomitant medications and Section 9.5 for targeted SAEs reporting requirements.
See Section 9.5 for reporting requirement for non-serious CRS events Grade ≥ 3.
The investigator must address the below AEs: 

Adverse event diagnosis or syndrome (if not known, signs or symptoms)

Dates of onset and resolution

Severity

Assessment of relatedness to investigational product, chemotherapy or study procedures

Action taken
Adverse event grading scale used will be the NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.03.  A copy of the grading scale can be downloaded from the CTEP 
home page (http://ctep.cancer.gov).  Cytokine Release Syndrome events will also be reported 
using the grading scale outlined in the KTE-X19 IB. 
In reviewing adverse events, investigators must assess whether the adverse event is possibly 
related to 1) leukapheresis, 2) bridging chemotherapy, 3) CSF prophylaxis, 4) Conditioning 
chemotherapy, 5) the investigational product (KTE-X19), or any protocol required study 
procedure.  The relationship is indicated by a yes or no response and entered into the CRF.  A 
yes response should indicate that there is evidence to suggest a causal relationship between the 
study treatment or procedure and the adverse event.  Additional relevant data with respect to 
describing the adverse event will be collected in the CRFs.


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Amendment 7
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The investigator is expected to follow reported adverse events until stabilization or resolution.  If 
a subject begins a new anti-cancer therapy, the AE reporting period for non-SAEs ends at the 
time the new treatment is started.
9.3.
Definition of Serious Adverse Events
A 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
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. 

Results in persistent or significant disability/incapacity

Congenital anomaly/birth defect

Other medically important serious event
If an investigator considers an event to be clinically important, but it does not meet any of 
the serious criteria, the event could be classified as an SAE with the criterion of “other 
medically important serious event.” 

The terms “severe” and “serious” are not synonymous.  Severity refers to the intensity of an 
adverse event according to NCI CTCAE criteria; the event itself may be of relatively minor 
medical significance and, therefore, may not meet the seriousness criteria.  Severity and 
seriousness need to be independently assessed for each adverse event recorded on the CRF.

Progression of the malignancy during the study should not be reported as a AE.  However, 
signs and symptoms of disease progression may be recorded as AEs or SAEs and indicated 
as being due to disease progression in the CRF.  If the malignancy has a fatal outcome before 
the end of the SAE reporting period, the event leading to the death must be recorded as an 
SAE with the outcome of being fatal. 
9.3.1.
Hospitalization and Prolonged Hospitalization
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a SAE as described in Section 9.5.  


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The following hospitalization scenarios are not considered to be SAEs:

Hospitalization for palliative care or hospice care

Planned hospitalization required by the protocol (eg, for monitoring of the subject or to 
perform an efficacy measurement for the study)

Planned hospitalization for a pre-existing condition

Hospitalization due to progression of the underlying cancer
9.4.
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.  Every effort should be made to capture 
the established cause of death, which may become available later on (eg, after autopsy).
9.5.
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 Table 6 below, all SAEs will be reported within 
24 hours and recorded in the CRF.


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Amendment 7
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Table 6.
Reporting Requirements for Serious Adverse Events
Subjects who are screen-fails or who 
are enrolled, but do not receive KITE-
X19 infusion
Subjects who are enrolled and receive KITE-X19 infusion

SAEs that occur from signing of 
the latest informed consent form 
through 30 days after the last 
study specific procedure (eg, 
screening procedure, 
leukapheresis, bridging therapy, 
conditioning chemotherapy) or 
until initiation of a new anti-
cancer therapy, whichever occurs 
first, will be recorded in the CRF   

All SAEs that occur from signing of the screening informed 
consent form through 3 months after the KITE-X19 infusion or 
until initiation of another anti-cancer therapy, whichever occurs 
first

After 3 months, only targeted SAEs will be reported through 
24 months after KITE-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 SAEs.  Reporting of these SAEs will commence 
at the time the SCT preparative regimen commences through 
24 months after KTE-X19 infusion or disease progression, 
whichever occurs first, within 24 hours using the SAE Report Form 
and in the CRF.  

All SAEs deemed related to KITE-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
Abbreviations:  SAE, serious adverse event; GVHD, graft-versus-host-disease; CRF, case report form; ICF, informed consent form.
See Section 6.8 for concomitant medication and Section 9.2 for targeted AE reporting requirements.
Following completion of KTE-C19-103, any relevant information on ongoing SAEs must be 
submitted to Kite Patient Safety and Pharmacovigilance within 24 hours of the investigator’s 
knowledge of the event using the paper SAE Report Form and sent via email to the SAE 
Reporting mailbox: safety_FC@gilead.com
Subsequently, all SAEs will be reported to the health authorities per local reporting guidelines.
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. 


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Any pregnancy in a female subject enrolled in the study must be reported, regardless of the time 
after the KTE-X19 infusion. If pregnancy occurs in a female partner of a male subject within 6 
months after completing conditioning chemotherapy or the KTE-X19 infusion, 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 Kite. Pregnancy Report Forms should be reported to Kite Patient Safety and 
Pharmacovigilance via email: Safety_FC@gilead.com or fax: +1 (650) 522-5477.
The pregnancy itself or an induced elective abortion to terminate a pregnancy without medical 
reasons are not considered AEs. Any premature termination of a pregnancy (eg, spontaneous 
abortion, 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 
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. 
If a lactation case occurs in a female subject in the study, 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 
LTFU period. Report the lactation case and Special Situations Reporting Forms to Kite Patient 
Safety and Pharmacovigilance via email: Safety_FC@gilead.com or fax: +1 (650) 522-5477.
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 from the first 3-12 subjects 
treated with KTE-X19 and make recommendations on further study conduct and progression of 
the study based on the incidence of KTE-X19 DLT and review of serious adverse events.
Dose-limiting toxicity is defined as the following KTE-X19-related events with onset within the 
first 28 days following KTE-X19 infusion:

Grade 4 hematologic toxicity lasting more than 30 days (except lymphopenia) if not 
attributable to underlying disease

All KTE-X19-related grade 3 non-hematologic toxicities lasting for > 7 days and all 
KTE-X19-related grade 4 non-hematologic toxicities regardless of duration are considered 
DLTs, with the exception of the following which are not considered DLTs:


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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
CRS will be graded according to a revised grading system {Lee 2014}.  Adverse events 
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.
Three subjects will initially be enrolled to evaluate the safety of the KTE-X19 regimen.  Subjects 
will be evaluated for DLTs within the first 28 days following the completion of the KTE-X19 
infusion.  The analysis of DLTs will be based on the DLT evaluable set as defined in 
Section 10.5.  The SRT will make recommendations based on the incidence of DLT and overall 
safety profile of the KTE-X19 regimen as outlined below:

If the subject incidence of DLT is 0 of 3 subjects, the SRT may recommend either
proceeding to Phase 2 at 2 x 106 anti-CD19 CAR T cells/kg; or 
accrual of additional subjects in Phase 1 to further characterize risk/benefit prior to 
Phase 2

If the subject incidence of DLT is 1 of 3 subjects, the SRT may recommend either


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accrual of an additional 3 subjects at the same cell dose with re-evaluation of the 
incidence of DLT after a total of 6 subjects in the DLT evaluable set have been assessed 
for DLT.  In this case, the SRT may recommend accrual to Phase 2 if the cumulative 
incidence of DLT in the 6 subjects is ≤ 1 of 6 subjects; or 
evaluation of a lower dose of 1 x 106 anti-CD19 CAR T cells/kg in an additional set of 
3-6 subjects.  In this case, the SRT may recommend accrual to Phase 2 if the cumulative 
incidence of DLT is < 33%.

If the subject incidence of DLT is ≥ 2 of 3 subjects, a lower dose of 1 x 106 anti-CD19 CAR 
T cells/kg in an additional set of 3-6 subjects will be explored.  In this case, the SRT may 
recommend accrual to Phase 2 if the cumulative incidence of DLT is < 33%.
If the conditioning chemotherapy regimen and KTE-X19 dose evaluated in Phase 1 is 
determined to be safe based on the incidence of DLT, up to approximately 40 additional subjects 
(high and non-high burden disease) may be enrolled at 2 x 106 anti-CD19 CAR T cells/kg, 
1 x 106 anti-CD19 CAR T cells/kg, or 0.5 x 106 anti-CD19 CAR T cells/kg prior to commencing 
Phase 2. The data from these additional subjects will be reviewed by the SRT who will provide 
recommendations for dose for Phase 2.  Further details to be outlined in the SRT Charter.
Based on the review of all available safety and efficacy data, the benefit/risk  ratio was 
considered most favorable  at the dose of 1 x 106 anti-CD19 CAR T cells/kg, therefore the dose 
of 1 x 106 anti-CD19 CAR T cells/kg was considered the recommended Phase 2 dose. 
The final decision to commence Phase 2 and the dose selected for Phase 2 was formally 
communicated to participating sites in a separate communication.
9.8.
Data Safety Monitoring Board
An independent Data Safety Monitoring Board (DSMB) will be chartered to review safety data 
to make trial conduct recommendations. The DSMB will review safety data in an interim 
analysis during the Phase 2 portion of the study.  For this interim analysis, the DSMB will 
review safety data after 20 Phase 2 subjects have been treated with KTE-X19 and had the 
opportunity to be followed for 30 days after the KTE-X19 infusion.  During Phase 2, Kite 
Pharma or delegate will submit SAEs or suspected unexpected serious adverse reactions 
(SUSARs) to the DSMB chair for risk benefit analysis.  The DSMB Chair will review reported 
SAEs at least monthly and SUSARs as soon as received.  .  
9.9.
Criteria to Pause Enrollment
Study enrollment will be paused in Phase 1 (DLT Evaluation Period) following any grade 5 
adverse event that occurs within 30 days of KTE-X19 dosing regardless of attributions.  The 
DLT evaluation period is now complete (see Section 2.8).
As part of its oversight of the study, the DSMB also will assess criteria to pause enrollment in 
Phase 2 after 10, 20, and 35 subjects enrolled in Phase 2 have been treated with KTE-X19 and 
have had the opportunity to be followed for 30 days.  Enrollment will be paused if any of the 
following is met:


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Subject incidence of the following grade 4 KTE-X19-related adverse events lasting more than 
7 days is >33%:

Neurologic events

CRS (per Lee 2014 criteria)

Other non-hematological serious adverse event

Infection (treatment-related)


KTE-X19 
Protocol KTE-Cl9-103 
10_ 
• 
10.2. 
10.2.1. 
STATISTICAL CONSIDERATIONS 
-
Study Endpoints 
Primary 
Phase 1: Incidence of adverse events defined as dose-limiting toxicities (DL T) 
Kite Pha1ma, Inc. 
Amendment 7 
Phase 2: Overall complete remission rate (CR + CRi) per independent review (Appendix 1). All 
subjects that do not meet the criteria for CR or CRi by the analysis data cutoff date will be 
considered non-responders for the overall complete remission rate evaluation. 
10.2.2. 
Secondary 
• 
Duration of Remission (DOR): for subjects who experience CR or CRi per independent 
review, DOR is defined as the time between their first complete response per indepedent 
review to relapse or any death in the absence of documented relapse. Relapse is defined in 
Appendix 1. Subjects who do not meet the criteria for relapse and who have not died will be 
censored at the last evaluable disease assessment or disease status follow up assessment. A 
sensitivity analysis will be conducted in which non-disease mortality will be considered a 
competing risk. Disease assessments obtained after new anti-cancer therapies (including 
allogeneic SCT) will not conti·ibute to the derivation of duration of remission. The DOR for 
subjects that undergo allogeneic SCT while in remission is censored at the date of the 
allogeneic SCT; the DOR for subjects that undergo other new anti-cancer therapies in the 
absence of documented relapse is censored at the last evaluable disease assessment prior to 
the new anti-cancer therapies. 
• 
In subjects who achieve CR, a TKI may be resumed 2 months after KTE-X19 infusion. In 
such subjects who resume TKI therapy, disease assessments obtained after resumption of 
TKI therapy will conti·ibute to the derivation of the duration of remission. A sensitivity 
analysis will be conducted in which the duration of remission in such subjects is censored at 
the first date of the resumption of TKI therapy. 
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• 
Minimum Residual Disease (MRD) Negative Rate: The incidence of a minimal residual 
disease response (MRD-). MRD- is defined as MRD < 104 per the standard assessment (see 
Section 7.10). 
• 
Overall complete remission rate (CR + CRi) per investigator assessment (Appendix 1). 
• 
Allogeneic Stem Cell Transplant (Allogeneic SCT) Rate 
• 
Overall Survival: OS is defined as the time from 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 their last contact date. 
• 
Relapse-free Smvival (RFS): RFS is defined as the time from the KTE-X19 infusion date to 
the date of disease relapse or death from any cause. Subjects not meeting the criteria for 
relapse by the analysis data cutoff date will be censored at their last evaluable disease 
assessment date. Subjects who have not achieved a complete remission (CR or CRi) at the 
analysis data cutoff will be evaluated as having an RFS event at Day 0. 
• 
Incidence of adverse events and CTCAE grade changes in safety laborato1y values. 
• 
Incidence of anti-KTE-X19 antibodies. 
• 
Changes over time in the EQ-5D scale score and EQ-5D VAS score 
-
I 
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10.2.4. 
Covariates 
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Amendment 7 
The prima1y endpoints and selected secondaiy endpoints will be evaluated in subgroup analysis 
by subjects with or without prior blinatumomab, and by subjects with or without prior 
inotuzumab. Such subgroup analyses may not be perfonned if too few (eg, n < 5) subjects in the 
mITT set have received prior blinatumomab or prior inotuzumab at the time of the analysis. 
Additional covariates and subgroup analyses will be outlined in the Statistical Analysis Plan. 
10.3. 
Sample Size Considerations 
The anticipated enrollment in this study is approximately 100 subjects. 
The primaiy efficacy endpoint and all analyses based on the response will be based on a mITT 
population consisting of all subjects who receive any dose of KTE-X19 in Phase 2. 
This study uses a single-aim design to test for an improvement in overall complete remission 
rate. For the test of efficacy this study has approximately 93% power to distinguish between an 
active therapy with a 65% trne overall complete remission rate from a therapy with an overall 
complete remission rate of 40% or less with a I-sided alpha level of 0.025. A step-down test of 
the secondaiy endpoint MRD-negative Rate will be perfo1m ed against a MRD-negative rate of 
30% if the testing of the overall complete remission rate is significant. 
In Phase 1, the SRT will review safety data after 3 subjects in the DLT evaluable set (see 
Section 10.5) have had the opportunity to be followed for 28 days after the KTE-X19 infusion. 
If the conditioning regimen and KTE-X19 dose evaluated in Phase 1 is detennined to be safe 
based on the incidence of DLT, up to approximately 30 additional subjects may be enrolled to 
further evaluate safety prior to commencing Phase 2. 
During Phase 2, one interim and one prima1y analyses will be perfo1m ed. The interim analysis is 
for safety only and will occur after 20 subjects have been treated with KTE-X19 and have had 
the opportunity to be followed for 30 days after the KTE-X19 infusion. 
The primaiy analysis 
will occur when the overall study enrollment is complete and all subject in the mITT set have 
had the opportunity to complete the month 6 disease assessment. 65% Approximately 
100 subjects may be enrolled into the entire study. At the time of the primaiy analysis, in the 
event that either less than or more than 50 subjects ai·e eligible for the mITT set, all mITT 
eligible subjects will be included in the analysis. 
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10.4.
Statistical Assumptions
This study assumes that the underlying overall complete remission rate (in the absence of 
treatment with investigational therapy) is 40%.  For MRD- rate, it is assumed that the underlying 
response rate (in the absence of treatment with investigational therapy) is 30%.
10.5.
Analysis Subsets  
KTE-X19 will be administered as a single infusion at a target dose of 2 x 106 anti-CD19 CAR T 
cells/kg or 1 x 106 anti-CD19 CAR T cells/kg or 0.5 x 106 anti-CD19 CAR T cells/kg .  For 
subjects weighing greater than 100 kg, a maximum flat dose of 2 x 108 or 1 x 108 or 0.5 x 108 
anti-CD19 CAR T cells/kg may be administered.   Full Analysis Set:  the full analysis set will 
consist of all enrolled subjects and will be used for summaries of subject disposition.
Modified Intention-to-treat Set (mITT):  the modified intention-to-treat set will consist of all 
subjects enrolled in Phase 2 and treated with KTE-X19.  The mITT analysis set will be used for 
all efficacy analyses unless otherwise specified.
DLT-evaluable set: All Phase 1 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 a dose level has been 
evaluated for DLT and deemed safe.  Additional Phase 1 subjects enrolled and treated 
subsequently for the purpose 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 set is defined as all subjects treated with any dose of KTE-X19.
10.6.
Access to Individual Subject Treatment Assignments
This is a single arm, open-label study and subjects and investigators will be aware of treatment 
received.  Data handling procedures will be devised to reduce potential sources of bias and 
maintain the validity and credibility of the study.  These procedures will be outlined in the study 
statistical analysis plan, DSMB charter, and Trial Integrity Document.
10.7.
Interim Analysis
During Phase 1, the SRT will review safety data after 3 DLT evaluable subjects 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 as 
outlined in Section 9.6.
During Phase 2, the DSMB will review safety data after 20 Phase 2 subjects have been treated 
and followed for 30 days. The DSMB will also review SAEs on a monthly basis prior to the 
primary analysis.  The DSMB may request additional safety data or modifying the study conduct.  
The sponsor may request additional reviews by the DSMB if safety concerns are identified.  Data 
submitted to the DSMB may not have undergone completion of data cleaning procedures in 
order to facilitate timelines for DSMB review.


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10.8.
Planned Method of Analysis
The primary efficacy analysis will be performed when all subject in the mITT set have had the 
opportunity to complete the month 6 disease assessment.  Additional analyses may occur after 
the primary analysis has been completed.  These additional analyses will be descriptive and will 
occur after inferential testing has been performed.  The final analysis will occur when all subjects 
have completed the study.  
10.8.1.
Overall Complete Remission Rate
The incidence of response and exact 2-sided 95% confidence intervals will be generated.  An 
exact binomial test will be used to compare the observed response rate to a response rate of 40%.
10.8.2.
Duration of Remission
Duration of Remission (DOR): for subjects who experience CR or CRi per independent review, 
DOR is defined as the time between their first complete response per independent review to 
relapse or any death in the absence of documented relapse.  Relapse is defined in Appendix 1.  
Subjects who do not meet the criteria for relapse and who have not died will be censored at the 
last evaluable disease assessment or disease status follow up assessment. Disease assessments 
obtained after new anti-cancer therapies (including allogeneic SCT) will not contribute to the 
derivation of duration of remission. The DOR for subjects that undergo allogeneic SCT while in 
remission is censored at the date of the allogeneic SCT; the DOR for subjects that undergo other 
new anti-cancer therapies in the absence of relapse is censored at the last evaluable disease 
assessment prior to the new anti-cancer therapies.  Kaplan-Meier estimates and 2-sided 95% 
confidence intervals will be generated for DOR.  Estimates of the proportion of subjects 
remained as in complete remission at 3-month intervals will be provided.
A sensitivity analysis of DOR will be conducted in which non-disease mortality will be 
considered a competing risk. A competing-risk analysis method {Klein 2005, Putter 2007} will 
be used to estimate the cumulative incidence of relapse.  The cumulative incidence of relapse in 
the presence non-disease related mortality (the competing risk) will be estimated along with 2-
sided 95% confidence intervals at 3-monthly time intervals.  
10.8.3.
MRD-negative rate
The incidence of MRD-negative rate and exact 2-sided 95% confidence intervals will be 
generated.  If the statistical testing of the primary endpoint (overall complete remission rate) is 
significant, an exact binomial test will be used to compare the observed MRD-negative rate to a 
rate of 30% at a one-sided alpha level of 0.025.
10.8.4.
CR Rate, CRi Rate, and DOR to Treatment Among Subjects Retreated with 
KTE-X19 for Progressive Disease after Initial Remission
The incidence of CR rate, and CRi rate, and exact 2-sided 95% confidence intervals will be 
generated.


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DOR to retreatment is defined only for subjects who experience a CR or CRi to retreatment and 
is the time from the first complete remission after retreatment to relapse after retreatment or 
death due to disease relapse. The competing-risk analysis method will be used to estimate the 
cumulative incidence of relapse after retreatment.
10.8.5.
Overall Survival
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS.  
Estimates of the proportion of subjects alive at 3-month intervals will be provided.
10.8.6.
Allogeneic Stem Cell Transplant Rate
The incidence of Allogeneic SCT in the mITT set and 2-sided 95% confidence intervals will be 
generated.
10.8.7.
Safety
Subject incidence rates of adverse events including all, serious, fatal, CTCAE version 4.03 
grade 3 or higher and treatment related AEs reported throughout the conduct of the study will be 
tabulated by preferred term and/or system organ class.  CTCAE grade changes in safety 
laboratory values will be summarized with descriptive statistics.  The incidence of concomitant 
medications will be summarized.
Tables and/or narratives of deaths and treatment related SAEs will be provided.
10.8.8.
Long-term Data Analysis
All subjects will be followed for survival status for up to 15 years after receiving KTE-X19. 
LTFU data analysis will be performed on subjects in this study and after transition to the KT-US-
982-5968 LTFU study. No formal hypothesis testing will be performed based on data obtained 
after the cutoff for the primary analysis. Descriptive estimates of key efficacy and safety 
analyses may be updated to assess the overall treatment profile. 


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11.
REGULATORY OBLIGATIONS 
11.1.
Independent Review Board /Independent Ethics Committee 
A copy of the protocol, ICF and any additional subject or trial information such as subject 
recruitment materials must be submitted to each sites respective IRB/IEC for approval.  Once 
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 serious adverse 
events (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 contained at all material submitted to the key sponsor contact.  
The following rules are to be applied.

Subjects will be identified by a unique identification number

Date of birth or year of birth/age at time of enrollment will be reported according with local 
laws and regulations
For reporting of serious adverse events, subjects will be identified by their respective subject 
identification number, initials and data of birth (as per their local reporting requirements for both 
initials and date of birth)
Per federal regulations and ICH/GCP guidelines, investigators and institutions are required to 
permit authorization to the sponsor, 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 under the following criteria:

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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12.
PROTOCOL AMENDMENTS AND TERMINATION
If the protocol is amended, the investigators 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 and the investigator reserve the right to terminate the investigators 
participation in the study as per the terms of the agreement in the study contract.  The 
investigator is to provide written communication to the IRB/IEC of the trial completion or early 
termination and provide the CRO with a copy of the correspondence.
Kite Pharma reserves the unilateral right, at is sole discretion, to determine whether to 
manufacture KTE-X19 T cells and provide them to sites and subjects after the completion of the 
study and before treatment becomes commercially available.


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13.
STUDY DOCUMENTATION AND ARCHIVE
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated.  These individuals authorized to fulfil these responsibilities should be outlined and 
included in the Delegation of Authority Form.
Source documents are original documents, data and records for which the study data are 
collected and verified.  Example of such source documents may include, but are not limited to, 
hospital records and patient charts, laboratory, pharmacy, radiology and records, subject diaries, 
microfiches, correspondence and death registries.  Case report form entries may be considered as 
source data if the site of the original data collection is not available.  However use of the CRFs as 
source documentation as a routine practice is not recommended.
The investigator and study staff are responsible for maintaining a comprehensive and centralize 
filing system of all subject records that are readily retrieved to be monitored and or audited at 
any time by the key sponsor contact, regulatory authorities and IRB/IECs.  The filing system will 
include at minimum:

Subject content including ICFs and subject identification lists

Protocols and protocol amendments, investigator 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 and the investigator.  Should storage no longer be available to 
archive source documents or must be moved to an alternative location, the research staff should 
notify the key sponsor contact prior to the shipping the documents.


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


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15.
PUBLICATION
Authorship of publications from data generated in study KTE-C19-103 will be determined based 
on the uniform requirements for manuscripts submitted to biomedical journals (as outlined in the 
International Committee of Medical Journal Editors December 2013) which states: 

Authorship should be based on
Substantial contributions to the conception or design of the work, acquisition of data, 
analysis, or interpretation of data for the work AND
Drafting the article or revising it critically for important intellectual content; AND
Final approval of the version to be published; AND
Agreement to be accountable for all aspects of the work in ensuring that questions related 
to the accuracy or integrity of any part of the work re appropriately investigated or 
resolved
When a large, multicenter group has conducted the work, the group should identify the 
individuals who accept direct responsibility for the manuscript.  This individual should fully 
meet the criteria for authorship defined above.
Funding, collection of data or general supervision of the research alone or in combination does 
not qualify an individual for authorship.
Any publication, in any form, that is derived from this study must be submitted to Kite Pharma 
for review and approval.  The study contract between the institution, principal investigation and 
Kite Pharma or its delegate will outline the requirements for publication review.


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


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17.
REFERENCES
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Significance of Minimal Residual Disease in High Risk B-ALL: A Report from 
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residual disease tests in the management of acute lymphoblastic leukaemia. Br J 
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Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised 
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Kantarjian H, Gandhi V, Cortes J, Verstovsek S, Du M, Garcia-Manero G, et al. Phase 2 clinical 
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leukaemia in the elderly: characteristics and outcome with the vincristine-
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T cells for sustained remissions in leukemia. N Engl J Med 2014;371 (16):1507-
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Mitchell CD, Richards SM, Kinsey SE, Lilleyman J, Vora A, Eden TO, et al. Benefit of 
dexamethasone compared with prednisolone for childhood acute lymphoblastic 
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Br J Haematol 2005;129 (6):734-45.
Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, et al. 
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sulfate liposome injection for advanced, relapsed, and refractory adult 
Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol 
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Pui CH. Central Nervous System Disease in Acute Lymphoblastic Leukemia: Prophylaxis and 
Treatment. Hematology Am Soc Hematol Educ Program 2006;2006 (1):142-6.
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Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, et al. Induction therapy 
for adults with acute lymphoblastic leukemia: results of more than 1500 patients 
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Shah B, Huynh V, Sender LS, Lee DW, Castro JE, Wierda WG, et al. High Rates of Minimal 
Residual Disease-Negative (MRD−) Complete Responses (CR) in Adult and 
Pediatric and Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia 
(R/R ALL) Treated With KTE-C19 (Anti-CD19 Chimeric Antigen Receptor 
[CAR] T Cells): Preliminary Results of the ZUMA-3 and ZUMA-4 Trials. Blood 
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treatment after first relapse in adults with acute lymphoblastic leukemia initially 
treated by the LALA-94 trial. Leukemia 2007;21 (9):1907-14.
Terwey TH, Kim TD, Arnold R. Allogeneic hematopoietic stem cell transplantation for adult 
acute lymphocytic leukemia. Curr Hematol Malig Rep 2009;4 (3):139-47.
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relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, 
and prognosis with salvage therapy. Cancer 1999;86 (7):1216-30.
Topp MS, al. e. Blinatumomab improved overall survival in patients with relapsed or refractory 
Philadelphia negative B-cell precursor acute lympoblastic leukemia in a 
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Phase I/Phase II Study of Blinatumomab in Pediatric Patients With 
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(36):4381-9.


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18.
APPENDICES
Appendix 1.
OVERALL DISEASE RESPONSE CLASSIFICATION
Appendix 2.
EXTRAMEDULLARY DISEASE RESPONSE
Appendix 3.
SCHEDULE OF ASSESSMENTS FOR GERMAN SUBJECTS FOLLOWING 
KTE-X19 INFUSION


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Appendix 1.
OVERALL DISEASE RESPONSE CLASSIFICATION 
Response
BM
Peripheral Blood d
CNS
EMD
Non-CNS 
EMD b, e
CR
ANC ≥ 1,000 and Plt ≥ 100,000
CRi
ANC ≥ 1000 and Plt < 100,000
OR
ANC < 1000 and Plt ≥ 100,000
CRh
ANC ≥ 500 and Plt ≥ 50,000 
but not CR
Blast-free 
hypoplastic or 
aplastic BM
≤ 5% f
and
Any values not meeting criteria for 
CR, CRi or CRh
and
CNS-1
and
CR c
PR
All criteria for CR, CRi, CRh or blast-free hypoplastic or aplastic bone 
marrow are met
and
PR
Relapse
>5% f 
or
Circulating leukemia present a
or
CNS-2 or 
CNS-3
or
PD
No response
All required assessments are performed with failure to attain the criteria needed for any 
response category
Unknown
Assessment is not done, incomplete, or indeterminate
Note: Overall disease response can be assessed as ‘Relapsed disease’ if any single element of 
disease response assessment shows relapse, other Unknown elements of disease response 
assessment do not need to be evaluated
ANC = absolute neutrophil count; BM = bone marrow; EMD = extramedullary disease; Plt = platelets; 
a 
No circulating leukemia is < 1% circulating blasts by morphology; Circulating leukemia is ≥ 1% circulating blasts by 
morphology; If ≥ 1% blast by morphology and there is no other evidence of leukemia, then flow or molecular studies should 
be conducted to confirm that blasts are leukemia.
b 
See Overall Non-CNS EMD table (Appendix 2)
c 
If baseline EMD is present, then images must show CR.  If no baseline EMD, then images are not required, but if 
performed, must show CR per Appendix 2.
d 
ANC and Plt:  The units for Plt and ANC are per uL.  ANC and Plt values should be evaluated every time a BM evaluation 
is performed.  If not done, ANC and Plt values used for response assessment can be from any time 7 days prior to the BM 
result to any time after the BM result. 
e 
In subjects evaluated for non-CNS EMD, imaging and bone marrow results used for assessment of overall disease response 
must be within 30 days of each other
f 
Blasts by morphology in BM


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Appendix 2.
EXTRAMEDULLARY DISEASE RESPONSE
Subjects with known baseline extramedullary disease (EMD) should have disease assessed by 
the investigator per the Table below at baseline and post-baseline with an imaging modality 
appropriate for the anatomical site and clinical scenario (eg, MRI for CNS lesion, ultrasound for 
testicular lesion, CT for intra-abdominal or thoracic lesion) and with the same imaging modality 
throughout.  
Response a
PET
Baseline, 
On-study
Baseline lesion(s) 
(by CT or MRI) b
New Lesion(s)
Neg, N/A
and
All of:

Disappearance of measurable and non-measurable 
nodal lesions: 
o
Nodal masses >1.5 cm in greatest 
transverse diameter (GTD) at baseline 
must have regressed to ≤1.5 cm in GTD
o
Nodes that were 1.1 to 1.5 cm in their 
long axis and more than 1.0 cm in their 
short axis before treatment must have 
decreased to 1.0cm in their short axis 
after treatment

If testes, spleen and/or liver involvement, they 
must be normal size by imaging or physical 
examination.
and
No
CR
Pos, Neg
and
Any
and
No
PR
Any
and
All of:

≥ 50% decrease in sum of the product of the 
diameters (SPD) of up to 6 of the largest dominant 
masses. Dominant masses should be clearly 
measurable in at least 2 perpendicular dimensions, 
and should be from different regions of the body if 
possible. 

No increase in size of liver or spleen by imaging or 
physical exam

If multiple splenic and hepatic nodules are present, 
they must regress by ≥ 50% in the SPD. There 
must be a > 50% decrease in the greatest 
transverse diameter for a single nodule. 
and
No
SD
Does not meet the criteria for CR, PR, or PD
PD
Any
and
At least one of the following:

≥ 50% increase from nadir in the sum of the 
products of at least two lymph nodes, or if a single 
node is involved at least a 50% increase in the 
product of the diameters of this one node. 

At least a 50% increase in the longest diameter of 
any single previously identified node more than 1 
cm in its short axis

Greater than or equal to a 50% increase in size of 
splenic, hepatic or any other non-nodal lesion. 
or
Yes
Neg = Negative; Pos = Positive; N/A = Not applicable
a
Modified Revised IWG Criteria {Cheson 2007}
b
see Section 7.9.2 of protocol for details.


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Appendix 3.
SCHEDULE OF ASSESSMENTS FOR GERMAN SUBJECTS 
FOLLOWING KTE-X19 INFUSION
The post-infusion monitoring of subjects, described in section 7.11.7.2 in this protocol, will be 
extended by monitoring on Day 8, Day 9, and Day 10, according to procedures outlined in the 
Schedule of Assessment Table, column “IP administration period, 1-7”. The subject may stay 
hospitalized or return to the clinic daily for this extended monitoring at the discretion of the 
investigator.  
The daily monitoring will include vital signs (see section 7.4), blood draw for chemistry panel 
with CRP, ferritin (and LDH if indicated as per section 7.11.7.4), blood draw for CBC 
w/differential, and neurological assessment (see section 7.5). Any observed toxicity will be 
managed according to section 6.10 of this protocol. 

Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Phase 1/2 Multi-Center Study Evaluating the Safety and 
Efficacy ofKTE-X19 in Adult Subjects with 
Relapsed/Refractory B-precursor Acute Lymphoblastic 
Leukemia (r/r ALL) (ZUMA-3) 
Protocol Number: 
KTE-C19-103 (ZUMA-3) 
IND Number: 
016675 
EudraCT Number: 
2015-005009-35 
Clinical Study Sponsor: 
Kite Phanna, Inc. 
2400 Broadway 
Santa Monica, CA 90404 
United States of America 
Key Sponsor Contacts: 
[PD 
I 
I 
Kite Pharma, Inc. 
2400 Broadway 
Santa Monica, CA 90404 
Phone: IPPD 
I 
Email: [PPU 
I 
[PD 
I 
I 
Kite Pharma, Inc. 
2400 Broadway 
Santa Monica, CA 90404 
Phone: IPPD 
I 
Email: [PPU 
I 
Version: 
1.0 (Amendment #6) 
Date: 
31 October 2018 
Confidentiality Notice 
This document contains proprietary and confidential information of Kite Phanna Inc., a 
wholly owned subsidiary of Gilead Sciences, Inc. This information must not be disclosed 
to any third party without the prior written consent of Kite Phanna Inc. Questions regarding 
how this document should be used or the conduct of the clinical trial should be dfrected to the 
key sponsor contacts. 


CONFIDENTIAL
Page 2 of 100
31 October 2018
INVESTIGATOR’S AGREEMENT
I have read the attached protocol titled: A Phase 1/2 Multi-Center Study Evaluating the Safety 
and Efficacy of KTE-X19 in Adult Subjects with Relapsed/Refractory B-precursor Acute 
Lymphoblastic Leukemia (r/r ALL) (ZUMA-3) dated 31 October 2018 and agree to abide by all 
provisions set forth therein.
I agree to comply with the International Conference on Harmonisation Tripartite Guideline on 
Good Clinical Practice and applicable national or regional regulations and guidelines.
I agree and will ensure that financial disclosure statements will be completed by:

Me (including, if applicable, my spouse, legal partner and dependent children)

Sub-Investigators (including, if applicable their spouse, legal partner and dependent children)
at the start of the study and for up to 1 year after the study is completed at the start of 
the study and for up to one year after the study is completed.
I agree to ensure that the confidential information contained in this document will not be used for 
any purpose other than the conduct of the clinical investigation without prior written consent 
from Kite Pharma Inc.
____________________________________
Signature
____________________________________
Name of Investigator
____________________________________
Date
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 


KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
STUDY GLOSSARY 
Abbreviation 0 1· Term 
Definition/Explanation 
AE 
adverse event 
ALL 
acute lymphoblastic leukemia 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
CAR 
chimeric antigen receptor 
CAR+ 
chimeric antigen receptor positive 
CBC 
complete blood count 
CLL 
chronic lymphocytic leukemia 
CNS 
central nervous system 
CPF 
cell processing facility 
CR 
complete remission 
CRh 
complete remission response with pa1t ial hematologic recovery 
CRi 
complete remission response with incomplete hematologic recovery 
CRF 
case repo11 fonn 
CRS 
cytokine release syndrome 
CSF 
cerebrospinal fluid 
CTCAE 
common terminology criteria for adverse events 
ddPCR 
droplet digital polymerase chain reaction 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
DOR 
duration of remission 
DSMB 
data safety monitoring board 
DVT 
deep vein thrombosis 
eACT™ 
engineered autologous cell therapy 
ECHO 
echocardiogram 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EEG 
electroencephalogram 
End of Study for individual 
Defined as when the last day that protocol specified assessments are conducted 
subject 
for an individual subject 
End of Study (primary 
Defined as when the last subject is assessed or received an intervention for the 
completion) 
purposes of final collection of data for the primruy endpoint at Week 8 
End of Study ( end of trial) 
Defined as when the last subject is assessed or received an intervention for 
evaluation in the study, including sw-vival assessments 
High Burden Disease 
M3 maffow (>25% leukemic blasts) or :::: 1000 blasts/mm3 in the peripheral 
circulation 
HLH 
Hemophagocytic lymphohistiocytosis 
CONFIDENTIAL 
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KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
Abbreviation 0 1· Term 
Definition/Explanation 
ICF 
informed consent fonn 
IHC 
immunohistochemistiy 
IL 
interleukin 
IL-2R 
intedeukin-2 receptor 
IP 
investigational product 
1PM 
Investigational product manual 
IRB/IEC 
institutional review board/independent ethics committee 
KTE-X19 
autologous T cells transduced with retroviral vector containing anti-CD19 
CD28/CD3-zeta chimeric antigen receptor 
LMWH 
low-moleculru· weight heparin 
LTFU 
long tenn follow-up 
LVEF 
left ventricular ejection fraction 
mITT 
modified intend to treat 
MTD 
maximum tolerated dose 
MRD 
minimal residual disease 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NHL 
non-Hodgkin lymphoma 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cells 
PET 
positron emission tomography 
Ph+ 
Philadelphia clu·omosome positive 
PMBCL 
prima1y mediastinal B-cell lymphoma 
PD 
progressive disease 
PR 
pa1tial response 
qPCR 
quantitative polymerase chain reaction 
RCR 
replication competent retrovirns 
RFS 
relapse-fre.e survival 
r/r 
relapsed/refractory 
SAE 
serious adverse event 
scFv 
single chain variable fragment 
SMZL 
splenic marginal zone lymphoma 
SOA 
schedule of assessments 
soc 
standard of care 
SCT 
stem cell transplant 
Study day 0 
Defined as the first day that KTE-Xl9 is administered to the subject 
TEAEs 
treatment-emergent adverse events 
TKI 
tyrosine kinase inhibitor 
TLS 
tumor lysis syndrome 
CONFIDENTIAL 
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KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment 6 
Abbreviation 0 1· Term 
Definition/Explanation 
TNF 
tumor necrosis factor 
ULN 
upper limit normal 
WBC 
white blood cell 
CONFIDENTIAL 
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PROTOCOL SYNOPSIS
Title:
A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of 
KTE-X19 in Adult Subjects with Relapsed/Refractory B-precursor
Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)
Indication:
The indication is for the treatment of adult subjects with B-precursor r/r 
ALL.
Study Design:
ZUMA-3 is a Phase 1/2, multicenter, open-label study evaluating the 
safety and efficacy of KTE-X19 in adult subjects with relapsed or 
refractory B-precursor ALL.  In this study, relapsed or refractory is 
defined as one of the following: primary refractory; first relapse 
following a remission lasting ≤ 12 months; relapsed or refractory after 
second-line or higher therapy; relapsed or refractory after allogenic 
SCT (provided the transplant occurred ≥100 days prior to enrollment 
and that no immunosuppressive medications were taken ≤ 4 weeks 
prior to enrollment). 
Phase 1 Study
During Phase 1, approximately 3-12 subjects with high burden [M3 
marrow (>25% leukemic blasts) or ≥1000 blasts/mm3 in the peripheral 
circulation] r/r ALL disease who are evaluable for DLT 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 in Phase 1 or 
proceeding to Phase 2 based on the incidence of DLTs and overall 
safety profile of KTE-X19.  Up to approximately 40 additional subjects 
with high or low burden disease may be enrolled to further assess 
safety (see Figure 1, Section 3.1 and Section 9.6).  
Phase 2  Study
During Phase 2, approximately 50 subjects in the modified-intention to 
treat (mITT) set will be assessed to evaluate the efficacy and safety of 
KTE-X19.   
An independent Data Safety Monitoring Board (DSMB) will review 
safety data through one interim analysis during the Phase 2 portion of 
the study.  In this interim analysis, the DSMB will review safety data 
after 20 Phase 2 subjects have been treated with KTE-X19 and had the 
opportunity to be followed for 30 days after the KTE-X19 infusion.  
Each subject will provide consent and be evaluated for study 
participation.  Once deemed eligible and enrolled into the study, each 
subject will follow the same study treatment schedule and procedural 
requirements, independent of the phase of the study, and proceed 
through the following study periods:
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
Screening period 

Enrollment/Leukapheresis period

Bridging chemotherapy and cerebrospinal fluid (CSF) prophylaxis 
period

Conditioning chemotherapy period

Investigational Product (IP) treatment period

Post treatment assessment period

Long term follow-up period
For study requirements assigned to each study period, refer to the 
schedule of assessments and Section 7 for details.
Study Objectives:
Phase 1 Study
The primary objective of Phase 1 is to evaluate the safety of KTE-X19.  
Phase 2 Study
The primary objective of Phase 2 is to evaluate the efficacy of 
KTE-X19, as measured by the overall complete remission rate defined 
as complete remission (CR) and complete remission with incomplete 
hematologic recovery (CRi) in adult subjects with r/r ALL 
(Appendix 1).  Secondary objectives will include assessing the safety 
and tolerability of KTE-X19 and additional efficacy endpoints.
Hypothesis: 
This study is designed to differentiate between a treatment that has a 
true overall complete remission rate of 40% or less and a treatment 
with a true overall complete remission rate of 65% or more. The 
hypothesis is that the overall complete remission rate to KTE-X19 is 
significantly greater than 40%.
Primary 
Endpoints:

Phase 1: Incidence of adverse events (AEs) defined as dose-
limiting toxicities (DLTs) in the DLT evaluable set

Phase 2:  Overall complete remission rate (CR + CRi) per 
independent review (Appendix 1)
Secondary 
Endpoints:

Overall complete remission rate (CR + CRi) per investigator 
assessment (Appendix 1)

Duration of Remission (DOR)

Minimal Residual Disease (MRD) negative rate

Allogeneic stem cell transplant (Allogeneic SCT) rate

Overall survival (OS)

Relapse-free Survival (RFS)
KTE-C19 
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
Incidence of AEs and common terminology criteria for adverse 
events (CTCAE) grade changes in safety laboratory values 

Incidence of anti-KTE-X19 antibodies

Changes over time in the EQ-5D score and VAS score (phase 2 
only)
Exploratory Endpoints

Treatment-related mortality rate100 days post-allogeneic SCT

Complete remission with partial hematological recovery (CRh) 

Blast-free hypoplastic or aplastic bone marrow rate

Partial remission (PR) rate

The overall complete remission rate (CR +CRi), MRD-negative 
rate, and DOR among subjects retreated with KTE-X19 post-
progression

Level and activity of CAR+ T cells, as well as presence of CD19+ 
cells in blood and bone marrow

Levels of cytokines in serum and CSF
Sample Size
In total, up to approximately 100 subjects may be enrolled and treated 
with KTE-X19 in the study in Phase 1 and 2 combined (see 
Sections 9.6 and 10.3).   

Phase 1: Approximately 3-12 subjects evaluable for DLT and up to 
approximately 40 additional subjects

Phase 2: Approximately 50 subjects in the mITT set  
Study Eligibility
Please refer to Section 5 for a complete and detailed list of inclusion 
and exclusion criteria for both phases of the study.
Treatment
Bridging chemotherapy:

Bridging chemotherapy is recommended for all subjects 
particularly for those subjects with high disease burden at screening 
[M3 marrow (>25% leukemic blasts) or ≥1000 blasts/mm3 in the 
peripheral circulation]

If prescribed, bridging chemotherapy must be administered after 
leukapheresis and completed at least 7 days or 5 half-lives, 
whichever is shorter, prior to initiating conditioning chemotherapy.

Allowed bridging chemotherapy regimens are listed in Section 6.3, 
Table 2.  Doses listed are recommended and can be adjusted for 
age/comorbidities or per local or institutional guidelines.   

Refer to Sections 6.3 and 7.11.4 for further details.
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CSF Prophylaxis:

All subjects will receive CSF prophylaxis consisting of an 
intrathecal regimen according to institutional or national guidelines 
(eg, methotrexate 12 to 15 mg, cytosine arabinoside 40 mg, or 
dexamethasone 4 mg or equivalent steroid dose).  

CSF prophylaxis will be administered any time during screening 
(eg, at time of screening lumbar puncture) through 7 days prior to 
KTE-X19 infusion.  

Subjects who are enrolled with CNS-2 disease at baseline must 
receive CSF prophylaxis after leukapheresis and at least 7 days 
prior to KTE-X19 infusion, unless otherwise approved by the Kite 
Medical Monitor.   

Multiple doses of CSF prophylaxis can be given per investigator 
discretion in accordance with institutional guidelines, but at least 
7 days must pass between the last dose of CSF prophylaxis and 
KTE-X19 infusion.  

Additional CSF prophylaxis may be given post-KTE-X19 infusion 
per investigator discretion in accordance with institutional 
guidelines, but should be avoided for at least 8 weeks after 
KTE-X19 infusion if possible.  

Refer to Sections 6.4 and 7.11.5 for further details.
Conditioning Chemotherapy:

All subjects will receive conditioning chemotherapy consisting of 
fludarabine and cyclophosphamide.

Fludarabine will be given at a dose of 25 mg/m2/day intravenously 
(IV) over 30 minutes on Day-4, Day -3, and Day 2 prior to 
KTE-X19 infusion.

Cyclophosphamide will be given at a dose of 900 mg/m2/day IV 
over 60 minutes on Day -2 prior to KTE-X19 infusion. 

Refer to Sections 6.5 and 7.11.6 for further details. 
Investigational Product:

The day of KTE-X19 infusion is considered Day 0.

KTE-X19 infusion will be administered at a target dose of 2 x 106
anti-CD19 CAR T cells/kg, 1 x 106 anti-CD19 CAR T cells/kg, or 
0.5 x 106 anti-CD19 CAR T cells/kg (see Figure 1, Section 3.1 and 
Section 9.6). 

All subjects will be hospitalized to receive KTE-X19 infusion 
followed by a minimum 7 day observation period unless otherwise 
required by country regulatory agencies (refer to Appendix 3 for 
details).

Refer to Sections 6.6 and 7.11.7 for further details.
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Protocol KTE-C19-103  
Amendment 6 
 


KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment 6 
Procedures 
At specific time points as outlined in the schedule of assessments, 
subjects will undergo the following procedures: 
Safety Review 
T earn and Data 
Safety Monitoring 
Board 
CONFIDENTIAL 
• 
Collection of infonned consent, general medical histo1y including 
previous treatments for ALL, physical exam including height and 
weight, vital signs, ECOG perfonnance status, and neurological 
assessments. 
• 
Lumbar punctures for collection of cerebral spinal fluid (CSF). 
• 
Bone maITow biopsies/aspirates. 
I 
• 
Blood will be drawn and assessed locally for complete blood count 
(CBC) with differential, chemistry panels, C-reactive protein, and 
CD3 count. CD19 expression will be assessed locally in subjects 
with prior blinatumomab ti·eatment by flow cytometiy or 
immunohistochemistiy (IHC) on blasts obtained from peripheral 
blood or bone maiTow. 
• 
Women of child-beai·ing potential will undergo a urine or sennn 
pregnancy test. 
• 
Blood will be drawn and submitted to the centl'al lab for: -
lymphocyte subsets, anti-KTE-X19 antibodies, replication 
competent reti·ovirns (RCR) and anti-CD19 CART cell analysis. 
• 
Subjects will also undergo a baseline electi·ocardiogram (ECG) and 
echocai·diogram (ECHO) 
• 
Leukapheresis. 
• 
Routinely throu hout the conduct of the stud , subjects will be 
asked to repo1t 
adverse events. 
• 
Subjects in phase 2 will complete the EQ-5D questionnaire. 
During Phase 1, approximately 3-12 subjects with high burden [M3 
maITow (>25% leukemic blasts) or ~1000 blasts/mm3 in the peripheral 
circulation] r/r ALL disease who ai·e evaluable for DLT will be 
assessed to evaluate the safety ofKTE-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 finther emollment in Phase 1 or 
proceeding to Phase 2 based on the incidence of DLTs and overall 
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safety profile of KTE-X19.  Up to approximately 40 additional subjects 
with high or low burden disease may be enrolled to further assess 
safety (see Figure 1, Section 3.1 and Section 9.6).  
During Phase 2, approximately 50 subjects in the modified-intention to 
treat (mITT) set will be assessed to evaluate the efficacy and safety of 
KTE-X19.   
An independent Data Safety Monitoring Board (DSMB) will review 
safety data through one interim analysis during the Phase 2 portion of 
the study.  In this interim analysis, the DSMB will review safety data 
after 20 Phase 2 subjects have been treated with KTE-X19 and had the 
opportunity to be followed for 30 days after the KTE-X19 infusion.  
Statistical 
Considerations
The primary endpoint for the Phase 2 study is the overall complete 
remission rate (CR and CRi) per independent review (Appendix 1).  
This endpoint will be based on a mITT population consisting of all 
Phase 2 subjects who receive KTE-X19 dose (see Section 10.5).  
This study uses a single-arm design to test for an improvement in 
overall complete remission rate.  For the test of efficacy this study has 
approximately 93% power to distinguish between an active therapy 
with a 65% true overall complete remission rate from a therapy with an 
overall complete remission rate of 40% or less with a 1-sided alpha 
level of 0.025.  
During Phase 1, the SRT will review safety data after 3 subjects in the 
DLT evaluable set (see Section 10.5) have had the opportunity to be 
followed for 28 days after the KTE-X19 infusion (see Section 9.6).  
During Phase 2, one interim and one primary analysis will be 
performed.  The interim analysis is for safety only and will be 
performed by the DSMB after 20 Phase 2 subjects have been treated 
with KTE-X19 and had the opportunity to be followed for 30 days after 
the KTE-X19 infusion.  Additional interim analyses for safety may be 
requested by the DSMB.  
The primary analysis will occur when the overall study enrollment is 
complete and the last treated subject in the mITT set has had the 
opportunity to complete the month 6 disease assessment.  
A secondary endpoint, MRD-negative rate, will be tested against an 
MRD-negative rate of 30% if the testing of the primary endpoint is 
significant.
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Protocol KTE-C19-103  
Amendment 6 
 


KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
Study Schema 
CSF Prouhylaxis t 
Conditioning ChemotheraQY 
Investigational Product (!P) 
-0 
& 
Period 
Treatment Period 
0 ..... 
-0 
(/) 
1--; 
• ;;j 
Bridging 
V 
0 
V 
. 
Fludarabine 25 mg/m2/day 
A... 
·c 
1--; 
Chemotherapy 
Subject is hospitalized prior 
V 
V 
i::: 
A... 
..c: 
IV over 30 minutes on Day -
to KTE-Xl9 infusion 
V 
0 
0. 
E 
ro 
4, Day -3 and Day -2. 
KTE-X19 is infused 
::I 
t>.O 
..:.:: 
(/) 
I 
i::: 
(/) 
::I 
intravenously on Day 0 
V 
·5 
V 
(/) 
.9 
Cyclophosphamide 900 
(/) 
V 
----
mg/m2/day IV over 60 
<t:: 
0 
ts 
-
µ.., 
(/) 
i::: 
minutes on Day -2 only 
i::: 
§ 
V 
V 
.§ 
Day -1: Rest 
§ 
V 
0 
ro 
r-' 
V 
tJJ 
l:l 
i::: 
U.l 
0 
(/) 
0 
A... 
t CSF Prouhylaxis (administered any time during screening through 7 days mior to KTE-Xl9 infusion): 
All subjects will receive CSF prophylaxis consisting of an intrathecal regimen according to institutional or national guidelines must be administered. CSF prophylaxis 
may be administered with the screening lumbar puncture. See Section 6.4 for additional details. 
* Bridging Chemotherapy (administered after leukapheresis and completed at least 7 days or 5 half-lives, whichever is shorter, prior to initiating 
conditioning chemotherapy) 
Bridging chemotherapy is recommended for all subjects particularly those subjects with high disease burden at screening [M3 marrow (>25% leukemic blasts) or 
:C::1000 blasts/mm3 in the peripheral circulation]. See Section 6.3 for details. 
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TABLE OF CONTENTS
INVESTIGATOR’S AGREEMENT.............................................................................................................................2
STUDY GLOSSARY....................................................................................................................................................3
PROTOCOL SYNOPSIS ..............................................................................................................................................6
TABLE OF CONTENTS ............................................................................................................................................13
LIST OF IN-TEXT TABLES......................................................................................................................................15
LIST OF IN-TEXT FIGURES ....................................................................................................................................15
1.
OBJECTIVES.....................................................................................................................................................16
2.
DISEASE BACKGROUND AND RATIONALE..............................................................................................17
2.2.
Diagnosis and Subtyping of ALL...........................................................................................................17
2.3.
Philadelphia Positive vs. Negative ALL ................................................................................................17
2.4.
Treatment and Prognosis........................................................................................................................17
2.4.1.
First-line Treatment..............................................................................................................18
2.4.2.
Second-line and Beyond Treatment .....................................................................................18
2.4.3.
Minimal Residual Disease (MRD) .......................................................................................20
2.5.
Study Rationale......................................................................................................................................20
2.5.1.
CD19 and Expression...........................................................................................................20
2.6.
Clinical Experience with Anti-CD19 CAR T Cells in Studies Conducted at the National 
Cancer Institute (NCI)............................................................................................................................21
2.7.
KTE-C19-101 ZUMA-1 Experience......................................................................................................21
2.8.
KTE-X19-103 ZUMA-3 Phase 1 Experience ........................................................................................22
3.
KTE-X19-103 STUDY DESIGN .......................................................................................................................23
3.1.
General Study Design ............................................................................................................................23
3.2.
Participating Sites...................................................................................................................................24
3.3.
Number of Subjects................................................................................................................................24
3.4.
Replacement of Subjects........................................................................................................................25
3.5.
Study Duration .......................................................................................................................................25
3.5.1.
Study Duration for Individual Subjects................................................................................25
3.5.2.
Completion of Study ............................................................................................................25
4.
SUBJECT SCREENING AND ENROLLMENT...............................................................................................26
5.
SUBJECT ELIGIBILITY ...................................................................................................................................27
5.1.
Inclusion Criteria....................................................................................................................................27
5.2.
Exclusion Criteria...................................................................................................................................28
6.
PROTOCOL TREATMENT ..............................................................................................................................31
6.1.
Treatment Terminology..........................................................................................................................31
6.2.
Leukapheresis (within approximately 5 days of eligibility confirmation) .............................................31
6.3.
Bridging Chemotherapy.........................................................................................................................31
6.4.
CSF Prophylaxis.....................................................................................................................................32
6.5.
Conditioning Chemotherapy ..................................................................................................................33
6.5.1.
Fludarabine...........................................................................................................................33
6.5.2.
Cyclophosphamide...............................................................................................................33
6.5.3.
Mesna ...................................................................................................................................33
6.5.4.
Rationale for Conditioning Chemotherapy Choice and Dose ..............................................34
6.6.
KTE-X19................................................................................................................................................34
6.6.1.
Rationale for KTE-X19 Dose...............................................................................................35
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6.7.
Concomitant Therapy.............................................................................................................................35
6.8.
Excluded Medications............................................................................................................................36
6.9.
Subsequent Therapy...............................................................................................................................37
6.10.
Toxicity Management ............................................................................................................................38
7.
STUDY PROCEDURES ....................................................................................................................................39
7.1.
Informed Consent...................................................................................................................................39
7.2.
Demographic Data .................................................................................................................................39
7.3.
Medical and Treatment History..............................................................................................................39
7.4.
Physical Exam, Vital Signs, Performance Status, and European Quality of Life-5 Dimensions 
(EQ-5D) .................................................................................................................................................40
7.5.
Neurological Assessment .......................................................................................................................40
7.6.
Cardiac Function ....................................................................................................................................40
7.7.
Lumbar Puncture....................................................................................................................................41
7.8.
Laboratory..............................................................................................................................................41
7.9.
Disease Assessments..............................................................................................................................43
7.9.1.
Bone Marrow Evaluation .....................................................................................................43
7.9.2.
Imaging Requirements (Only Applies to Subjects with Known Non-CNS 
Extramedullary Disease at Baseline)....................................................................................45
7.10.
Biomarkers.............................................................................................................................................45
7.11.
Procedures by Study Period ...................................................................................................................47
7.11.1.
Screening..............................................................................................................................47
7.11.2.
Rescreening..........................................................................................................................49
7.11.3.
Enrollment/Leukapheresis....................................................................................................49
7.11.4.
Bridging Chemotherapy Period............................................................................................51
7.11.5.
CSF Prophylaxis Period .......................................................................................................51
7.11.6.
Conditioning Chemotherapy and KTE-X19 Infusion...........................................................52
7.11.7.
Investigational Product Treatment Period............................................................................55
7.11.8.
Post-treatment Assessment Period .......................................................................................59
7.11.9.
Long-term Follow-up Period................................................................................................60
7.11.10.
Retreatment ..........................................................................................................................62
8.
SUBJECT WITHDRAWAL...............................................................................................................................70
8.1.
Reasons for Removal from Treatment ...................................................................................................70
8.2.
Reasons for Removal from Study ..........................................................................................................71
9.
SAFETY REPORTING......................................................................................................................................72
9.1.
Adverse Events.......................................................................................................................................72
9.1.1.
Diagnosis Versus Signs and Symptoms ...............................................................................72
9.1.2.
Abnormal Vital Sign Values ................................................................................................73
9.1.3.
Reporting Abnormal Laboratory Findings ...........................................................................73
9.2.
Reporting of Adverse Events .................................................................................................................73
9.3.
Definition of Serious Adverse Events....................................................................................................75
9.3.1.
Hospitalization and Prolonged Hospitalization ....................................................................76
9.4.
Reporting Deaths....................................................................................................................................76
9.5.
Reporting of Serious Adverse Events ....................................................................................................76
9.6.
Pregnancy and Lactation........................................................................................................................77
9.7.
Safety Review Team and Dose-limiting Toxicity..................................................................................78
9.8.
Data Safety Monitoring Board ...............................................................................................................80
9.9.
Criteria to Pause Enrollment ..................................................................................................................80
10.
STATISTICAL CONSIDERATIONS................................................................................................................81
10.1.
Hypothesis..............................................................................................................................................81
10.2.
Study Endpoints .....................................................................................................................................81
10.2.1.
Primary.................................................................................................................................81
10.2.2.
Secondary.............................................................................................................................81
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10.2.3.
Exploratory Endpoints..........................................................................................................82
10.2.4.
Covariates.............................................................................................................................83
10.3.
Sample Size Considerations...................................................................................................................83
10.4.
Statistical Assumptions ..........................................................................................................................84
10.5.
Analysis Subsets.....................................................................................................................................84
10.6.
Access to Individual Subject Treatment Assignments ...........................................................................84
10.7.
Interim Analysis.....................................................................................................................................84
10.8.
Planned Method of Analysis ..................................................................................................................85
10.8.1.
Overall Complete Remission Rate .......................................................................................85
10.8.2.
Duration of Remission..........................................................................................................85
10.8.3.
MRD-negative rate...............................................................................................................85
10.8.4.
CR Rate, CRi Rate, and DOR to Treatment Among Subjects Retreated 
with KTE-X19 for Progressive Disease after Initial Remission...........................................85
10.8.5.
Overall Survival ...................................................................................................................86
10.8.6.
Allogeneic Stem Cell Transplant Rate .................................................................................86
10.8.7.
Safety....................................................................................................................................86
10.8.8.
Long-term Data Analysis .....................................................................................................86
11.
REGULATORY OBLIGATIONS......................................................................................................................87
11.1.
Independent Review Board /Independent Ethics Committee.................................................................87
11.2.
Subject Confidentiality...........................................................................................................................87
11.3.
Investigator Signatory Obligations.........................................................................................................87
12.
PROTOCOL AMENDMENTS AND TERMINATION ....................................................................................88
13.
STUDY DOCUMENTATION AND ARCHIVE ...............................................................................................89
14.
STUDY MONITORING AND DATA COLLECTION.....................................................................................90
15.
PUBLICATION..................................................................................................................................................91
16.
COMPENSATION .............................................................................................................................................92
17.
REFERENCES ...................................................................................................................................................93
18.
APPENDICES ....................................................................................................................................................97
Appendix 1.
OVERALL DISEASE RESPONSE CLASSIFICATION......................................................98
Appendix 2.
EXTRAMEDULLARY DISEASE RESPONSE....................................................................99
Appendix 3.
SCHEDULE OF ASSESSMENTS FOR GERMAN SUBJECTS FOLLOWING 
KTE-X19 INFUSION ..........................................................................................................100
LIST OF IN-TEXT TABLES
Table 1.
Complete Response (CR) Rate in Adult B-Precursor Acute Lymphoblastic 
Leukemia (B-ALL) in the Relapsed/Refractory Setting.........................................................19
Table 2.
Bridging Chemotherapy Regimens ........................................................................................32
Table 3.
Reporting Requirements for Concomitant Medications .........................................................36
Table 4.
Schedule of Assessments........................................................................................................65
Table 5.
Reporting Requirements for Adverse Events .........................................................................74
Table 6.
Reporting Requirements for Serious Adverse Events ............................................................77
LIST OF IN-TEXT FIGURES
Figure 1.
Phase 1 Dosing .......................................................................................................................24
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1.
OBJECTIVES
The primary objective of Phase 1 is to evaluate the safety of KTE-X19.  
The primary objective of Phase 2 is to evaluate the efficacy of KTE-X19, as measured by the 
overall complete remission rate defined as complete remission (CR) and complete remission with 
incomplete hematologic recovery (CRi) in adult subjects with relapsed/refractory B-precursor 
acute lymphoblastic leukemia (r/r ALL).  Secondary objectives will include assessing the safety 
and tolerability of KTE-X19, additional efficacy endpoints, and change in EQ-5D scores.
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Protocol KTE-C19-103  
Amendment 6 


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Kite Phruma, Inc. 
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2_ 
DISEASE BACKGROUND AND RATIONALE 
2.2. 
Diagnosis and Subtyping of ALL 
Diagnosis of ALL requires at least 20% lymphoblasts in the bone man ow (Harris et al, 1999). 
ALL is then further classified into 1 of 3 major subtypes by immunophenotyping: B-precursor 
ALL (70%), mature B-cell ALL (Burkitt lymphoma; 5%), and T-cell ALL (25%). B-cell ALLs 
are generally CDIO+, CD19+, and CD79a+, although precursor B-cell ALLs may be CD10-. 
Mature B-cell ALLs additionally express surface immunoglobulin (lg). T-cell ALLs express 
T-cell markers such as CD3, CD4, and CD8. The 3 immunophenotypic subtypes are associated 
with non-overlapping prognoses and ti·eatments making the classification clinically relevant 
(National Comprehensive Cancer Network 2014). B-precursor ALL comprises the majority of 
all adult ALL cases. 
2.3. 
Philadelphia Positive vs. Negative ALL 
Approximately 20-30% of adults and a small percentage of children with ALL are Philadelphia 
chromosome positive (Ph+), and the majority of Ph+ cases are of B-cell lineage (Lee et al, 2011). 
Ph+ status confers poor prognosis, with a 5-year event-free smv ival (EFS) rate of 36% vs 16% 
and an OS rate of 41 % vs. 22% in Philadelphia chromosome negative (Ph-) vs. Ph+ patients 
(Moonnan et al, 2007). Ph+ status also allows for additional ti·eatment with Abl tyrosine kinase 
inhibitors (TKis) such as imatinib or dasatinib. 
2.4. 
Treatment and Prognosis 
Several anti-neoplastic agents are given in vaiy ing doses and schedules based on regional 
preferences and patient tolerability in 3 distinct phases for 1st line ti·eatment: induction, 
intensified consolidation, and maintenance. Centi·al ne1vous system (CNS) prophylaxis 
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accompanies induction and consolidation.  The goals of treatment are to reconstitute normal 
hematopoiesis, prevent emergence of resistant subclones, eliminate minimal residual disease, and
provide prophylaxis to sanctuary sites.  Stem cell transplant also plays a role in the management 
of ALL, and tyrosine kinase inhibitors are added to chemotherapy and transplant regimens in 
patients with Ph+ disease.
2.4.1.
First-line Treatment
Most first-line regimens are a variation of either the Berlin-Frankfurt-Münster/Children’s 
Oncology Group (BFM/COG) regimens, which include a combination of vincristine, an 
anthracycline, a corticosteroid, and L-asparaginase, or the Cancer and Leukemia Group B 
(CALGB) regimens, which include the 4 drug classes above plus cyclophosphamide (Larson et 
al, 1995; Rowe et al, 2005).  A TKI such as imatinib is included in the treatment regimen for 
patients with Ph+ disease.  Dexamethasone appears to decrease the risk of CNS relapse and 
improve EFS compared to prednisone, but at the risk of increased toxicity and no OS advantage
(Mitchell C. D. et al, 2005; Pui 2006).  The hyper-CVAD regimen which has demonstrated 
efficacy in ALL is a variation on the CALGB regimen with alternating regimens of 
hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone with high-
dose methotrexate and cytarabine (Kantarjian et al, 2004).  First-line regimens yield CR rates of 
80-90% in adults.  Despite the high CR rates and a median duration of first remission of at least 
18 months, most patients eventually relapse. 
2.4.2.
Second-line and Beyond Treatment
The salvage setting represents the area of greatest need in adult ALL given the poor outcomes 
achieved with chemotherapy in adults who have relapsed or refractory ALL.  Second-line 
chemotherapy yields remissions in about 20-40% of patients, with the remission rate being lower 
in patients who relapse within 12 months of an initial response (Table 1).  
In the third line and beyond setting, complete remissions with chemotherapy are seen in at most 
20% of patients, and the majority of remissions are short lived (Thomas et al, 1999; Kantarjian et 
al, 2003; Fielding et al, 2007; Tavernier et al, 2007; Faderl et al, 2011; O'Brien et al, 2013).  
Although long-term disease free survival (DFS) rates of autologous stem cell transplantation 
(ASCT) are superior to chemotherapy in the salvage setting (approximately 40% vs 20%), only 
30-40% of patients who achieve a second CR are eligible for SCT, and fewer than half of the 
patients who achieve a second CR have enough time prior to relapse to make it to transplant
(Herzig et al, 1987; Kolb et al, 2009; Terwey et al, 2009), with rates as low as 5% in adults being 
reported in some series (Thomas et al, 1999).  
In December 2014, the bispecific CD19-directed CD3 T-cell engaging agent blinatumomab was 
granted accelerated approval in the US for the treatment of Ph- relapsed or refractory B-cell 
precursor ALL (blinatumomab USPI).  The approval was granted based primarily on findings 
from a single-arm study of 185 evaluable patients with r/r B-precursor ALL (relapsed with first 
remission duration of ≤12 months in first salvage or relapsed or refractory after first salvage 
therapy or relapsed within 12 months of SCT).  CR was achieved in 32% of patients, and an 
additional 9% had CRh.  The majority of responses (81%) occurred within cycle 1 of treatment, 
75% of those with CR/CRh had an minimum residual disease (MRD)-negative response, and the 
SCT rate among those who achieved CR/CRh was 39%.  Duration of response/relapse-free 
survival in patients who had CR/CRh was 5.9 months.  Results from a second study of 
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blinatumomab, a Phase 3 ti·ial which randomized adults with r/r ALL 2:1 to blinatumomab 
versus 1 of 4 standard of care (SOC) chemotherapy regiments, have also recently been repo1ied. 
A total of 405 patients were randomized, and a prespecified interim analysis occun ed after 
248 deaths. Median OS was 7.8 months (95% CI: 5.7, 10.0) for blinatumomab and 4.0 months 
(95% CI: 2.9, 5.4) for SOC (p=.011; hazard ratio=0.71), smpassing the prespecified boundaiy p 
value of 0.0183. Based on these results, this study was terminated early upon the 
recommendation of the study's Data Safety Monitoring Boai·d (Topp and al 2016). No studies 
have yet repo1ied the outcomes of patients in the post-blinatumomab setting. 
Table 1 below summarizes representative data in the salvage setting for adult ALL. Given the 
promising early data for chimeric antigen receptor (CAR) T-cell therapy in r/r ALL (see 
Section 2.6), this u-ial evaluates KTE-X19 in this difficult setting. 
Table 1. 
Complete Response (CR) Rate in Adult B-Precursor Acute 
Lymphoblastic Leukemia (B-ALL) in the Relapsed/Refractory Setting 
Tlial/Reference 
Treatment 
Crite1i a 
N 
CR rate 
Second line chemotherapy (relapsed or refractory afte1· initial thei-apy for de novo disease) 
TI1omas Cancer 1999 
Various 
Primary refracto,y (24 % ) 
314 
chemotherapy or 
or prima,y relapsed (76%) 
SCT regimens 
disease 
Tavemier Leukemia 
Various systemic 
Relapsed or refractory after 
340 
2007 
or SCT regimens 
initial therapy, Ph· 
Relapsed or refractory after 
81 
initial therapy, Ph+ 
Welbom Am J Hema 
Various 
Relapsed or refractory 
609 
1994 
chemotherapy 
ALL (primarily second line 
reginiens 
patients) 
Fader! Clin 
hCVAD 
Refractory (11 %) or 
90 
Lymphoma Myeloma 
relapsed (89%; 76% of all 
Leuk 2011 
patients in 151 relapse) 
Third line or beyond chemotherapy 
Kanta,jian Blood 
Clofarabine 
2nd or subsequent salvage 
2003 
Advani Br J Haematol 
Clofarabine+ 
Patients in 2nd relapse 
2010 
cytarabine 
O'Brien JCO 2013 
Liposomal 
Ph· ALL in 2nd or greater 
vincristine sulfate 
relapse 
Novel targeted agents 
Blinatumomab USP! 
Blinatumomab 
Relapsed/refracto,y 
B-precursor ALL 
Kanta,jian NEJM 
Anti-CD22-
Relapsed and refracto,y 
2016 
calecheamicin 
ALL 
(inotuzumab 
oogamicin) 
A 
Complete remission with incomplete hematologic recovery (CRi) 
B 
Complete remission with pa,tial hematologic recovery (CR11) 
C 
Complete marrow response (CMR) 
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Page 19 of 100 
8 
16 
65 
185 
49 (46 
adults) 
31% overall 
• 22% for patients with 1st CR of 
dm·ation 1-11.9 months (n=146) 
• 41 % for patients with first CR of 
dm·ation > 12 months (n=93) 
• 20% for Ph+ (n=55) 
• 34% for prima,y refracto,y (n=75) 
46% 
37% 
34% 
46% (median CRl of responders = 
16 months) 
13% 
19% (CR/CRi)A 
20% (CR/CRi)A 
• 32%CR 
• 9% CR11B 
• 36% CR 
• 45%CRiA 
• OS HR 0.77 (97.5% CI, 0.58-1.03) 
inotuzumab vs. chemotherapy 
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2.4.3.
Minimal Residual Disease (MRD)
Several studies have shown that the achievement of a minimum residual disease (MRD)-negative 
response (<0.01% lymphoblasts in the bone marrow) with ALL treatment is associated with 
prolonged leukemia remission in both pediatric and adult ALL patients (Campana 2010; 
Cazzaniga et al, 2011).  However, not all subjects who achieve a morphological complete 
remission achieve a MRD-negative remission.  In a large study by the Children’s Oncology 
Group randomizing patients to different induction and maintenance regimens, 1788 of 2422 
(74%) of subjects who had a remission (<10% bone marrow blasts) achieved MRD-negative 
status (Borowitz et al, 2015).  Treatment with the bispecific T cell engager blinatumomab 
produces a similar proportion of MRD-negative responses, 8 of 14 (53%) pediatric patients with 
a CR had an MRD-negative response {von Stackelberg 2016}.  Minimum residual disease-
negative rates are similar in adults.  With blinatumomab, 60 of 73 (82%) adult patients who 
achieved a CR or CRh had an MRD-negative response.
2.5.
Study Rationale
Most advanced cancers eventually become refractory to conventional therapies and new 
treatment modalities are needed.  Immunotherapy, which is based on the enhancement of an 
immune response against the tumor, is a promising approach to treating many cancer types.  
T cells play an important role in destroying diseased cells throughout the body.  Studies with 
immune checkpoint inhibitors and tumor infiltrating lymphocytes have demonstrated the 
potential of T cells to treat cancer.  T cells need to possess the appropriate specificity for a tumor, 
be present in sufficient numbers, and overcome any local immunosuppressive factors to be 
effective.  Engineered T cells are a promising approach for cancer therapy (Kershaw et al, 2013).
Engineered Autologous Cell Therapy (eACT™) is a process by which a patient’s own T cells are 
collected and subsequently genetically altered to recognize and target antigens expressed on the 
cell surface of specific malignancies (Kochenderfer et al, 2013). The ability to genetically 
engineer human T cells and use them to mediate cancer regression in patients has been 
demonstrated in a number of studies (Davila et al, 2014; Maude et al, 2014; Lee et al, 2015) and 
has opened possibilities for the treatment of patients with a wide variety of cancer types 
including B-cell malignancies expressing the CD19 antigen.
Given the poor outcomes which have been achieved to date in adults with r/r ALL (Table 1), this 
trial will enroll adult subjects with r/r B-precursor ALL as evidenced by failure to achieve or 
maintain a response to prior systemic therapy, or by recurrence after allogeneic SCT. Patients 
with T-cell lineage ALL will not be enrolled since their malignancies are CD19- and will likely
not respond to a CD19 directed agent.  
2.5.1.
CD19 and Expression
CD19 is a 95 kD transmembrane protein expressed only in the B-cell lineage. It is expressed in 
all normal B cells starting at the pre-B cell stage until the final differentiation stage and is not 
expressed in pluripotent hematopoietic stem cells or most plasma cells.  The pattern of CD19 
expression is maintained in B-cell malignancies including all subtypes of B-cell non-Hodgkin 
lymphoma (NHL), chronic lymphocytic leukemia (CLL), and non T-cell acute lymphoblastic 
leukemia (ALL) (Blanc et al, 2011) with the exception of multiple myeloma.
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2.6. 
Clinical Experience with Anti-CD19 CART Cells in Studies Conducted at 
the National Cancer Institute (NCI) 
Refer to the cmTent KTE-X19 IB and publications cited for details on the study design and the 
safety and efficacy outcomes observed in these studies. 
2.7. 
KTE-C19-101 ZUMA-1 Experience 
ZUMA-I is a Phase 1-2 multicenter, open-label study evaluating the safety and efficacy of 
KTE-C19 in adult subjects with refracto1y DLBCL, PMBCL, and transfonned follicular 
lymphoma (TFL). The primaiy analysis for the study, which has been completed, was based on 
analysis of the data from 92 subjects in the phase 2 portion of the study who had the opportunity 
to be followed for at least 6 months after infusion of KTE-C 19. The study met its primaiy 
endpoint: the objective response rate per International Working Group 2007 criteria (Cheson et 
al, 2007) in these 92 subjects was 82% (95% CI: 72%, 89%), which was significantly higher than 
the pre-specified control rate of 20% (p < 0.0001; (Locke et al, 2017)). 
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Refer to the current KTE-C19 IB for a summary of the safety and efficacy findings from this 
study.  
2.8.
KTE-X19-103 ZUMA-3 Phase 1 Experience
ZUMA-3 is a study of KTE-X19 in adults with r/r ALL (see Section 3).  The DLT evaluation 
period of the study was completed with no DLTs observed in the 2 x 106 anti-CD19 CAR T 
cells/kg dose cohort.  Additional subjects have been enrolled and treated in the phase 1 portion of 
the study at 1 x 106 anti-CD19 CAR T cells/kg and 0.5 x 106 anti-CD19 CAR T cells/kg.  
Forty-five patients were dosed in the Phase 1 portion of study across the 3 dose levels. Based on 
the risk-benefit ratio observed, the dose of 1 x 106 anti-CD19 CAR T cells/kg was considered the 
recommended Phase 2 dose.
Refer to the current KTE-X19 IB for a summary of the safety.  
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3.
KTE-X19-103 STUDY DESIGN
3.1.
General Study Design
ZUMA-3 is a Phase 1/2, multicenter, open-label study evaluating the safety and efficacy of 
KTE-X19 in adult subjects with relapsed or refractory B-precursor ALL. In this study, relapsed 
or refractory is defined as one of the following: primary refractory; first relapse following a 
remission lasting ≤ 12 months; relapsed or refractory after second-line or higher 
therapy; relapsed or refractory after allogenic SCT (provided the transplant occurred ≥100 days 
prior to enrollment and that no immunosuppressive medications were taken ≤ 4 weeks prior to 
enrollment). 
During Phase 1, approximately 3-12 subjects with high burden [M3 marrow (>25% leukemic 
blasts) or ≥1000 blasts/mm3 in the peripheral circulation] r/r ALL disease who are evaluable for 
DLT will be assessed to evaluate the safety of KTE-X19. A 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 in Phase 1 or proceeding to Phase 2 based on the 
incidence of DLTs and overall safety profile of KTE-X19.  Additionally, approximately 
40 subjects with high or low burden disease may be enrolled to further assess safety (see 
Figure 1 and Section 9.6).  
During Phase 2, approximately 50 subjects in the mITT set will be assessed to evaluate the 
efficacy and safety of KTE-X19.  
In total, up to approximately 100 subjects may be enrolled and treated with KTE-X19 in the 
study in Phase 1 and 2 combined (see Section 9.6 and Section 10.5).  
During Phase 2, one interim and one primary analysis will be performed.  The interim analysis is 
for safety only and will be performed by an independent DSMB after 20 Phase 2 subjects have 
been treated with KTE-X19 and had the opportunity to be followed for 30 days after the 
KTE-X19 infusion (see Section 10.7).  Additional interim analyses for safety may be requested 
by the DSMB.  
The primary analysis will occur when the overall study enrollment is complete and the last 
treated subject in the mITT set has had the opportunity to complete the month 6 disease 
assessment (see Section 10.8).  
Each subject will provide consent and be evaluated for study participation. Once deemed 
eligible and enrolled into the study, each subject will follow the same study treatment schedule 
and procedural requirements, independent of the phase of the study, and proceed through the 
following study periods:

Screening period

Enrollment/Leukapheresis period

Bridging chemotherapy and CSF prophylaxis period
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
Conditioning chemotherapy period

Investigational Product (IP) treatment period

Post treatment assessment period

Long term follow-up period
For study requirements assigned to each study period, refer to the schedule of assessments 
(SOA) and Section 7 for details.  A study schema is drawn out and described at the end of the
protocol synopsis section.
Figure 1.
Phase 1 Dosing
3.2.
Participating Sites
Approximately 35 centers located in North America, Europe, and potentially other regions will 
participate in this study.  During the conduct of the study, additional regions, countries or sites 
may be added as necessary.
Sites that do not enroll a subject within 4 months of site activation may be considered for 
closure.
3.3.
Number of Subjects
Participants in this trial will be referred to as “subjects”. Up to approximately 100 subjects may 
be enrolled into the entire study in order to obtain 3-12 subjects evaluable for DLT in the Phase 1 
portion, up to approximately 40 additional Phase 1 subjects, and approximately 50 subjects in the 
mITT set in the Phase 2 portion of the study.
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It should be noted that Kite Pharma may choose to close enrollment at any time. Refer to the 
statistical considerations section of the protocol for sample size estimations.
3.4.
Replacement of Subjects
Subjects will continue to be enrolled until the specified numbers of subjects are attained in the 
DLT evaluable (Phase 1) and mITT sets (Phase 2).
Subjects who have not received the required dose of KTE-X19 in order to be included in DLT 
evaluable set will be retained in the analyses of disposition and safety, where appropriate (see 
Section 10.5). 
3.5.
Study Duration
3.5.1.
Study Duration for Individual Subjects 
The duration of the study for individual subjects will vary. For a subject who completes the 
entire protocol from the date of informed consent through the completion of the long term 
follow-up period, the duration of the study will take approximately 15 years to complete.
However, individual study duration will vary depending on a subject’s screening requirements, 
response to treatment and survival.
The need for prolonged follow-up is based on the potential persistence of gene transfer vectors in 
treated subjects.
3.5.2.
Completion of Study
Completion of the study is defined as the time at which all enrolled subjects complete the long 
term follow-up period visit, is considered lost to follow-up, withdraws consent, or dies. 
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4.
SUBJECT SCREENING AND ENROLLMENT
All subjects must sign and date the IRB/IEC approved consent form before initiating any study 
specific procedures or activities that are not part of a subject’s routine care. Refer to Section 7
for details.
Each subject who enters the screening period will receive a unique subject identification number
at the time of consent [refer to the Investigational Product Manual (IPM)]. This number will be 
used to identify the subject throughout the study and must be used on all study documentation 
related to the subject.
Furthermore, the subject identification number must remain constant throughout the entire 
clinical study, it must not be changed after enrollment or if the subject is rescreened or retreated
(see Section 7.11.10 for details regarding retreatment).
Once a subject commences leukapheresis, the subject will be considered enrolled into the study.
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5.
SUBJECT ELIGIBILITY
5.1.
Inclusion Criteria
101)
Relapsed or refractory B-precursor ALL defined as one of the following:

Primary refractory disease

First relapse if first remission ≤ 12 months

Relapsed or refractory disease after two or more lines of systemic therapy

Relapsed or refractory disease after allogeneic transplant provided subject is at least 
100 days from stem cell transplant at the time of enrollment and off of 
immunosuppressive medications for at least 4 weeks prior to enrollment
102)
Morphological disease in the bone marrow (> 5% blasts)
103)
Subjects with Ph+ disease are eligible if they are intolerant to tyrosine kinase inhibitor 
(TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 
2 different TKIs
104)
Age 18 or older
105)
Eastern cooperative oncology group (ECOG) performance status of 0 or 1
106)
ANC ≥ 500/µL unless in the opinion of the PI cytopenia is due to underlying leukemia 
and is potentially reversible with leukemia therapy 
107)
Platelet count ≥ 50,000/µL unless in the opinion of the PI cytopenia is due to underlying 
leukemia and is potentially reversible with leukemia therapy 
108)
Absolute lymphocyte count ≥ 100/µL
109)
Adequate renal, hepatic, pulmonary and cardiac function defined as:

Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min 

Serum ALT/AST ≤ 2.5 x ULN (upper limit normal)

Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert’s syndrome.

Left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial effusion 
as determined by an ECHO, no NYHA class III or class IV functional classification, 
and no clinically significant arrhythmias

No clinically significant pleural effusion

Baseline oxygen saturation > 92% on room air
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110)
Females of childbearing potential must have a negative serum or urine pregnancy test 
111)
In subjects previously treated with blinatumomab, CD19 tumor expression on blasts 
obtained from bone marrow or peripheral blood must be documented after completion of 
the most recent prior line of therapy.  If CD19 expression is quantified, then blasts must 
be ≥ 90% CD19 positive.
5.2.
Exclusion Criteria
201)
Diagnosis of Burkitt’s leukemia/lymphoma according to WHO classification or chronic 
myelogenous leukemia lymphoid blast crisis
202)
History of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, 
cervix, bladder, breast) unless disease free for at least 3 years 
203)
History of severe hypersensitivity reaction to aminoglycosides or any of the agents used 
in this study
204)
CNS abnormalities

Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample 
of CSF with ≥ 5 WBCs per mm3 with or without neurological changes, and 

Presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a sample 
of CSF with <5 WBCs per mm3 with neurological changes 
Note: Subjects with CNS-1 (no detectable leukemia in the CSF) and those with 
CNS-2 without clinically evident neurological changes are eligible to participate in 
the study. 

History or presence of any CNS disorder such as a seizure disorder, cerebrovascular 
ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with 
CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral 
edema
205)
History of concomitant genetic syndrome associated with bone marrow failure such as 
Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome
206)
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or 
other clinically significant cardiac disease within 12 months of enrollment
207)
History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of 
enrollment.  
208)
Primary immunodeficiency 
209)
Known infection with HIV, hepatitis B or hepatitis C virus.  A history of hepatitis B or 
hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or 
nucleic acid testing.
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210)
Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring 
antimicrobials for management.  Simple UTI and uncomplicated bacterial pharyngitis are 
permitted if responding to active treatment and after consultation with the Kite Medical 
Monitor
211)
Prior medication: 

Salvage systemic therapy (including chemotherapy, TKIs for Ph+ ALL, and 
blinatumomab) within 1 week or 5 half-lives (whichever is shorter) prior to 
enrollment 

Prior CD19 directed therapy other than blinatumomab

History of CTCAE grade 4 neurologic event or grade 4 CRS (Lee et al, 2014) with 
prior CD19-directed therapy

Treatment with alemtuzumab within 6 months prior to enrollment, clofarabine or 
cladribine within 3 months prior to enrollment, or PEG-asparaginase within 3 weeks 
prior to enrollment

Donor lymphocyte infusion (DLI) within 28 days prior to enrollment

Any drug used for GVHD within 4 weeks prior to enrollment (eg, calcineurin 
inhibitors, methotrexate, mycophenolyate, rapamycin, thalidomide), or 
immunosuppressive antibody used within 4 weeks prior to enrollment (eg, anti-CD20,
anti-tumor necrosis factor, anti-interleukin 6 or anti-interleukin 6 receptor)

At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory 
immune checkpoint molecule therapy prior to enrollment (eg, ipilimumab, 
nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists etc) 

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 enrollment
212)
Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling 
Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter).  Ommaya 
reservoirs and dedicated central venous access catheters such as a Port-a-Cath or 
Hickman catheter are permitted 
213)
Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute 
or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment 
214)
Live vaccine ≤ 4 weeks prior to enrollment
215)
Women of child-bearing 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
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216)
Subjects of both genders of child-bearing potential who are not willing to practice birth 
control from the time of consent through 6 months after the completion of KTE-X19
217)
In the investigators judgment, the subject is unlikely to complete all protocol-required 
study visits or procedures, including follow-up visits, or comply with the study 
requirements for participation
218)
History of autoimmune disease (eg, Crohns, rheumatoid arthritis, systemic lupus) 
resulting in end organ injury or requiring systemic immunosuppression/systemic disease 
modifying agents within the last 2 years
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Amendment6 
6_ 
PROTOCOL TREATMENT 
6.1. 
Treatment Terminology 
The following te1ms will be used to describe and define protocol treatment: 
• 
Bridging chemotherapy refers to treatment used to control a subject's disease prior to 
conditioning chemotherapy. 
• 
CSF prophylaxis will be administered prior to infusion of conditioning chemotherapy. 
• 
The Conditioning chemotherapy regimen used for this study will be fludarabine and 
cyclophosphamide. 
• 
The investigational product for this study is named KTE-X19. 
6.2. 
Leukapheresis (within approximately 5 days of eligibility confirmation) 
Before leukapheresis commences, the criteria outlined in Section 7 .11. 3 must be met. 
Subjects will undergo leukapheresis to obtain leukocytes (white blood cells) for the manufacture 
of KTE-X19. Leukapheresed cells obtained from subjects at paiiicipating centers will be 
shipped to the Cell Processing Facility (CPF) overnight as described in the 1PM. 
The leukapheresed cells ai·e then 
packaged for expedited shipment to the CPF as described in the 1PM. 
See Section 6.8 for excluded medications prior to leukapheresis. 
6.3. 
Bridging Chemotherapy 
Bridging therapy may be administered after leukapheresis and prior to conditioning 
chemotherapy at the investigators discretion. Bridging chemotherapy is recollllllended for all 
subjects paii iculai·ly those subjects with high disease burden at baseline [M3 maITow (>25% 
leukemic blasts) or 
1000 blasts/mm3 in the peripheral circulation]. If prescribed, bridging 
chemotherapy must be administered after leukapheresis and completed at least 7 days or 5 half-
lives, whichever is sho1ier, prior to initiating conditioning chemotherapy. 
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Allowed bridging chemotherapy regimens are outlined in Table 2. Doses listed are 
recommended, and can be adjusted for age/comorbidities or per local or institutional guidelines. 
Table 2. 
Bridging Chemotherapy Regimens 
Bridging Chemotherapy Regimen • 
Attenuated V AD: Vincristine non-liposomal 
DOMP: Dexamethasone 6 mg/m2/day PO ( or IV) divided BID 
(1-2 mg IV weekly) or liposoma.l (2.25 mg/m2 IV 
days 1-5, vincristine 1.5 mg/m2 (maximum dose 2 mg) IV on 
weekly), and dexamethasone 20-40 m . IV or PO 
day 1, methotrexate 20 mg/m2 PO weekly, 6-MP 50-
dail x 3-4 <la. s er week. 
75mg/m2/day PO daily 
Mercaptopurine (6-MP): 50-75 mg/m2/da.y by 
mouth (administer at bedtime on an empty 
stomach to improve abso1ption) 
Hydroxyurea: Doses titrated between 
15-50 mg/kg/day (rounded to the nearest 500 mg 
capsule and given as a single daily oral dose on a. 
continuous basis) 
Attenuated FLAG/FLAG-IDA: fludarabine 30 mg/m2 IV days 
1-2, cytarabine 2 g/m2 IV days 1-2, G-CSF 5 µg/kg SC or IV 
struts on day 3 and can continue until day before the strut of 
conditioning chemotherapy. With or without idarubicin 
6 mg/m2 IV days 1-2. 
Mini-hyper CV AD ( courses A and/or B): 
Course A: Cyclophosphamide 150 mg/m2 q 12 hrs x 3 days, 
dexamethasone 20 mg/d IV or PO daily days 1-4 and 11-14, 
vincristine 2 mg IV x 1 
Course B: methotrexate 250 mg/m2 IV over 24h on day 1, 
cytarabine 0.5 g/m2 IV ql2h x 4 doses on days 2 and 3. 
a 
Use of a TKI in combination with any of the above regimens is allowed for subjects with Ph+ ALL and Ph-like ALL 
6.4. 
CSF Prophylaxis 
All subjects will receive CSF prophylaxis consisting of an intrathecal regimen according to 
institutional or national guidelines (eg, methoti·exate 12 to 15 mg, cytosine arabinoside 40 mg, or 
dexamethasone 4 mg or equivalent steroid dose). 
CSF prophylaxis will be administered any time during screening ( eg, at time of screening lumbar 
puncture) through 7 days prior to KTE-X19 infusion. 
Subjects who are emolled with CNS-2 disease at baseline must receive CSF prophylaxis after 
leukapheresis and at least 7 days prior to KTE-X19 infusion, unless othe1w ise approved by the 
Kite Medical Monitor. 
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Multiple doses of CSF prophylaxis can be given per investigator discretion in accordance with 
institutional guidelines, but at least 7 days must pass between the last dose of CSF prophylaxis 
and KTE-X19 infusion.  
Additional CSF prophylaxis may be given post-KTE-X19 infusion per investigator discretion in 
accordance with institutional guidelines, but should be avoided for at least 8 weeks after 
KTE-X19 infusion if possible.  
Should a subject have an Ommaya reservoir and there is no evidence of blockage of CSF flow 
from the spinal canal, administration of CSF prophylaxis through the reservoir is acceptable. 
6.5.
Conditioning Chemotherapy
Conditioning chemotherapy refers to fludarabine and cyclophosphamide used for 
lymphodepletion prior to administration of KTE-X19.  Subjects will receive conditioning 
chemotherapy from Day -4 through day -2.  
Conditioning chemotherapy will be supplied by the investigative site unless otherwise 
noted.
Refer to the current product label for guidance on packaging, storage, preparation, 
administration and toxicity management associated with the administration of 
chemotherapy agents.
The investigational medicinal product (KTE-X19) must be available before initiation of 
conditioning chemotherapy.
See Section 7.11.6.1 for conditioning chemotherapy procedures. 
6.5.1.
Fludarabine
Fludarabine phosphate 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.
6.5.2.
Cyclophosphamide
Cyclophosphamide is a nitrogen mustard-derivative alkylating agent.  Following conversion to 
active metabolites in the liver, cyclophosphamide functions as an alkylating agent; the drug also 
possesses potent immunosuppressive activity.  The serum half-life after IV administration ranges 
from 3-12 hours; the drug and/or its metabolites can be detected in the serum for up to 72 hours 
after administration.  
6.5.3.
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 will be administered 
around the cyclophosphamide dose according to institutional standards.
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6.5.4.
Rationale for Conditioning Chemotherapy Choice and Dose
The rationale for the conditioning chemotherapy regimen and dose selection is based on the 
Phase 1 study conducted at the Pediatric Oncology Branch at the NCI (Lee et al, 2015). In this 
study, 21 subjects (20 with ALL) were treated and all received the same fludarabine and 
cyclophosphamide schedule with a favorable benefit/risk profile. 
Consistent with the NCI protocol (Lee et al, 2015), the KTE-X19-103 study will use the same 
Conditioning chemotherapy regimen consisting of fludarabine at a dose of 25 mg/m2/day IV over 
30 minutes on Day -4, Day -3, Day -2 prior to KTE-X19 and cyclophosphamide at a dose of 
900 mg/m2/day IV over 60 minutes on Day -2 prior to KTE-X19. Day -1 will be a rest day.  The 
3-day conditioning chemotherapy regimen may be administered in an outpatient setting in 
accordance with the daily dosing instructions outlined in Section 7.11.6.2. 
Following completion of each subjects’ conditioning chemotherapy regimen, subjects will 
receive their respective KTE-X19 infusion.  
6.6.
KTE-X19
The IP for this study is KTE-X19.
Refer to the most current Investigator’s Brochure regarding KTE-X19 and clinical 
experience.  This section contains general information and is not intended to provide specific 
instructions.  Refer to the IPM for details and instruction on storage and administration of 
KTE-X19.  
KTE-X19 is supplied cryopreserved in cryostorage bags.  
 
  The cryostorage bags containing KTE-X19 arrive frozen in 
a liquid nitrogen dry shipper.  The bags must be stored in vapor phase of liquid nitrogen and the 
product remains frozen until the subject is ready for treatment to assure viable live autologous 
cells are administered to the subject. Several inactive ingredients are added to the product to 
assure viability and stability of the live cells through the freezing, thawing, and infusion process.
KTE-X19 is a subject-specific product and the intended subject will be identified by a unique 
subject ID number.  Upon receipt, verification that the product and subject-specific labels match 
the subject’s information (eg, initials, subject ID number) is essential.  Do not infuse the product 
if the information on the subject-specific label does not match the intended subject.  The volume 
of KTE-X19 infused, the thaw start/stop time, and KTE-X19 infusion start/stop time, will be 
noted in the subject medical record. The product must not be thawed until the subject is ready 
for the infusion.  
To date, subjects have received doses of anti-CD19 CAR T cells ranging from 0.5 - 30 x 106
anti-CD19 CAR T cells/kg.  There have been no instances of accidental overdose of subjects in 
this program.  In case of accidental overdose, treatment should be supportive.  Corticosteroid 
therapy may be considered if any dose is associated with severe toxicity (see Section 6.8 for 
more information related to corticosteroid use).
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6.6.1. 
Rationale for KTE-X19 Dose 
In the ZUMA-3 study, the initial 6 subjects were ti·eated at 2 x 106 anti-CD19 CART cell/kg, 
with a subsequent group of 14 subjects ti·eated at 1 x 106 anti-CD19 CART cell/kg. No DLTs 
were observed in the DLT evaluable set, no drop off was seen in efficacy between the 2 x 106 
anti-CD19 CART cell/kg and 1 x 106 anti-CD19 CAR T cell/kg KTE-X19 doses and there was 
no clear difference in the safe 
rofile Section 2.8· Shah et al 2016 
CAR T ceWkg was considered the recommended Phase 2 dose. 
For subjects weighing greater than 100 kg, a maximum flat dose of 2 x 108 or 1 x 108 or 0.5 x 108 
anti-CD19 CART cells ma be administered. See Sections 9.6 for details. 
6.7. 
Concomitant Therapy 
Concomitant therapy refers to treatment that subjects receive during the conduct of the 
study. 
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Investigators may additionally prescribe any other concomitant medications or treatment deemed 
necessary to provide adequate supportive care, including growth factor support (eg, G-CSF) and 
routine anti-emetic prophylaxis and treatment except those medications listed in the excluded 
medication Section 6.8.  
In subjects with Ph+ disease and who achieve CR, a TKI may be resumed 2 months after 
KTE-X19 infusion at the investigator discretion and in accordance with institutional guidelines. 
See Section 3, Table 2 for use of TKI’s during bridging chemotherapy.
The investigator is responsible for reporting all concomitant medications as follows in 
Table 3:
Table 3.
Reporting Requirements for Concomitant Medications
Subjects who are pre-
screen or screen-fails
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 from the 
date of the pre-
screening informed 
consent or screening 
informed consent 
through 30 days after 
the last study-specific 
pre-screening or 
screening procedure, 
respectively.

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 anti-cancer 
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.  (excluding 
allogeneic SCT)

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.  
o
In subjects who received 
allogeneic SCT, only concomitant 
medications related to a KTE-X19-
related serious adverse event 
(SAE) will be recorded.  Reporting 
of these concomitant medications 
will commence at the time the 
SCT preparative regimen 
commences.
See Section 6.9 regarding documentation of subsequent anticancer therapy.
6.8.
Excluded Medications
Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to 
leukapheresis and 5 days prior to KTE-X19 infusion.  
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Systemic corticosteroids should be avoided as premedication in subjects for whom CT scans 
with contrast are contraindicated (ie, subjects with contrast allergy or impaired renal clearance).  
If possible, such subjects should undergo non-contrast CT scans or alternative imagine modality 
(such as MRI) instead. 
Corticosteroids and other immunosuppressive drugs should also be avoided for 3 months after 
KTE-X19 infusion, unless used to manage KTE-X19 related toxicities (Refer to the most 
current version of the IB; see Section 6.4).  Other medications which may interfere with 
evaluation of KTE-X19, such as non-steroidal anti-inflammatory agents should also be avoided 
for the same time 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.  If a subject requires the initiation of therapeutic anticoagulant 
doses prior to initiation of conditioning chemotherapy or prior to KTE-X19 infusion, then 
conditioning chemotherapy/KTE-X19 infusion must be held and the case discussed with the Kite 
Medical Monitor.
For subjects with Ph+ ALL, all TKIs must be stopped at least 1 week prior to KTE-X19 infusion, 
including but not limited to imatinib, dasatinib, and ponatinib.  In subjects who achieve CR, a 
TKI may be resumed 2 months after KTE-X19 infusion. See Section 6.3, Table 2 for use of 
TKIs during bridging chemotherapy.
CSF prophylaxis may be given post-KTE-X19 infusion per investigator discretion in accordance 
with institutional guidelines, but should be avoided for at least 8 weeks after KTE-X19 infusion 
if possible.  
Treatment for the subject’s leukemia such as chemotherapy, immunotherapy, targeted agents, 
radiation, high dose corticosteroid, other than defined/allowed in this protocol, and other 
investigational agents are prohibited except as needed for treatment of disease progression after
KTE-X19 infusion. If permissibility of a specific medication/treatment is in question, contact 
the Kite Pharma medical monitor.
Medications with sedative properties should be avoided if possible in the setting of neurologic 
events (refer to the KTE-X19 IB).
6.9.
Subsequent Therapy 
Subsequent therapy administered after KTE-X19 infusion for a subjects’ disease such as non-
study specified chemotherapy, immunotherapy, targeted agents, as well as stem cell transplant 
and radiation therapy will be recorded for all enrolled subjects until one of the following 
occur:  subject completes the long term follow up period, is considered lost to follow up, 
withdraws consent, or dies.  
For subjects who are enrolled, but do not receive KTE-X19 infusion, any additional anti-cancer 
therapy will also be collected until subject completes the long term follow up period, is 
considered lost to follow up, withdraws consent, or dies.
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6.10.
Toxicity Management
To date, the following important risks have been identified with KTE-X19: CRS, neurological 
events, infections, and cytopenias.  Refer to Section 6 of the current KTE-X19 IB for details 
regarding these events and management guidance. 
As the safety experience with KTE-X19 increases, the management guidance may be updated. 
Therefore, it is important that you always refer to the most current version of the KTE-X19 IB 
for guidance regarding managing KTE-X19 related toxicities. 
Additional information and management recommendations can also be found in the IB regarding 
important potential risks associated with KTE-X19 as well as possible complications associated 
with malignancy and cancer treatment.
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7.
STUDY PROCEDURES
Research staff should refer to the SOA for an outline of the procedures required. The visit 
schedule is calculated from KTE-X19 infusion on Day 0. 
An overview of study assessments/procedures is outlined below. A description for each period
of the study is provided in Section 7.11. Refer to the CRF completion guidelines for data 
collection requirements and documentation of study procedures.
7.1.
Informed Consent
Before a subject’s participation in the clinical study, the investigator is responsible for obtaining 
written informed consent from the subject after adequate explanation of the study design, 
anticipated benefits and the potential risks. Subjects should sign the most current Institutional 
Review Board/Independent Ethics Committee (IRB/IEC) approved Informed Consent form 
(ICF) prior to any study specific activity or procedure is performed.
The consent process and the subject’s agreement or refusal to participate in the study is to be 
documented in the subject’s medical records. If the subject agrees to participate, the ICF is to be 
signed and personally dated by the subject and by the person who conducted the informed 
consent discussion. The original signed ICF will be retained in accordance with institution 
policy and IRB/IEC requirements with a copy of the ICF provided to the subject.
All subjects who are enrolled into the study should be re-consented with any updated version of 
the IRB/IEC approved ICF if relevant to their participation in the study.
7.2.
Demographic Data
Demographic data will be collected 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 their possible association with subject safety and treatment effectiveness.
7.3.
Medical and Treatment History
Relevant medical history prior to the start of adverse event reporting will be collected. Relevant 
medical history is defined as data on the subject’s concurrent medical condition that would be 
typically shared in a referral letter. All findings will be recorded in the CRFs.
In addition to the medical history, all history related to the subject’s disease, treatment and 
response to treatment will be collected and must date back to the original diagnosis.
For subjects who are being referred from another clinic or institution to the participating research 
center, copies from the subject’s chart should be obtained.
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7.4.
Physical Exam, Vital Signs, Performance Status, and European Quality of 
Life-5 Dimensions (EQ-5D)
Physical exams will be performed during screening and at times noted 
. Changes 
noted in subsequent exams when compared to the baseline exam will be reported as an adverse 
event. 
During KTE-X19 infusion/hospitalization, vital signs including blood pressure, heart rate, 
oxygen saturation, and temperature will be monitored before and after the KTE-X19 infusion and 
then routinely (every 4-6 hours) while hospitalized. If the subject has a fever (temperature
38.3oC or greater) at any time during hospitalization, vital signs will be monitored more 
frequently as clinically indicated.
Performance status as measured by the ECOG scale will be performed to quantify the subject’s 
general well-being and ability to perform activities of daily life.
The EQ-5D will be completed only for subjects participating in phase 2.  The EQ-5D will be 
completed at the timepoints outlined in the SOA prior to other study related procedures or 
assessments.  Subjects who are blind or illiterate may have the EQ-5D questions read to them by 
the study staff.  The study staff, however, cannot interpret any of the questions for the subject.  A 
subject may be exempt from completing the questionnaire if he or she is unable to read the 
questionnaire in one of the country languages available.
The EQ-5D is a 2 page generic patient questionnaire for assessing the overall health status of a 
subject.  The EQ-5D consists of a 5 dimension descriptive system including questions on 
mobility, self-care, usual activities, pain/comfort, and anxiety/depression and a visual analogue 
scale (EQ VAS) which allows the respondent to record health on a vertical scale (eg, best health 
to worst health) thus allowing a quantitative measure of health outcome.  
7.5.
Neurological Assessment 
Subject’s 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 should be reported as an adverse 
event per Section 9.
7.6.
Cardiac Function 
Each subject’s cardiac function as measured by ECHO will be assessed during the screening 
period to confirm study eligibility. No evidence of pericardial effusion, as required by 
eligibility, will also be confirmed by ECHO.  
If the last chemotherapy regimen the subject received is not considered cardiotoxic, then an 
ECHO performed within 28 days prior to signing the consent may be used for eligibility.  
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Amendment6 
If the last chemotherapy regimen the subject received is considered cardiotoxic, then an ECHO 
perfo1med following the subjects last chemotherapy treatment and within 28 days prior to 
signing the consent may be used for confmnation of eligibility. 
A baseline chest x-ray will be completed within 14 days before emollment to confmn eligibility. 
To establish a baseline, an ECG will be perfo1med within 30 days before emollment. 
7.7. 
I 
I 
I 
I 
I 
Lumbar Puncture 
Subjects with CNS-2 will have a lumbar puncture performed at the screening visit for 
examination of CSF. In addition, a lumbar puncture may be performed as applicable for 
subjects with new onset of a Grade 2 or higher neurologic event after KTE-X19 infusion 
7.8. 
Laboratory 
The below samples will be collected at the time points indicated in the SOA. Additional samples 
( eg, blood, urine, other bodily fluids, tissue) may be collected as needed for further safety testing. 
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KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
Local Laboratory Analysis: 
• 
Bone maiTow evaluation for % blasts 
• 
Cerebral spinal fluid (total protein, WBC,. 
%blast by m01phological assessment, and 
gram stain and culture if clinically indicated or for neurological event) 
(bicai·bonate ), Creatinine, Glucose, 
bumin Calci 
• 
C-reactive protein 
• 
Complete Blood Count with differential (5-pait prefened, but 3-pait will be acceptable) 
I 
I 
• 
CD3 count based on peripheral blood 
• 
CD19 immunophenotyping by flow cytometi 
-
I 
I 
Central Laboratory Analysis: 
• 
Bone maiTow biopsy and aspirate samples collected for confnmation of diagnosis as well as 
disease assessment 
• 
Cerebral spinal fluid 
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
Blood draws for cytokine levels and PBMCs (for the analysis of lymphocyte subsets, 
anti-CD19 CART cells, and replication-competent retrovirus [RCR] analysis) 

Serum samples will also be drawn for anti-KTE-X19 antibodies 

Peripheral blood
7.9.
Disease Assessments
7.9.1.
Bone Marrow Evaluation
Bone marrow aspirates and biopsies will be collected throughout the study
  

Screening bone marrow evaluation:
If available, archival formalin-fixed paraffin embedded (FFPE) bone marrow block 
and/or slides used for the original diagnosis of ALL will be submitted to the central 
laboratory along with the pathology report.
A bone marrow aspirate and biopsy is required at screening and will be performed after 
the last dose of systemic chemotherapy and within approximately 14 days before 
enrollment to establish baseline disease.  
■
If there is a delay between when the screening bone marrow is performed and the 
apheresis, contact the Kite Medical Monitor for guidance on whether or not bone 
marrow evaluation needs to be repeated.  If a fresh bone marrow aspirate and biopsy 
was recently collected and properly stored prior to consent, then contact the Kite 
Medical Monitor to confirm if this sample is adequate for screening.  
In subjects who receive bridging chemotherapy, an additional bone marrow sample is 
required between the end of bridging chemotherapy and Day -4.  If bridging 
chemotherapy is not administered, then the additional bone marrow sample is not 
required, however, an assessment of peripheral circulating blasts is required (see 
Section 7.11.6.3 regarding requirement for peripheral blast count).  

On study bone marrow evaluations: 
A bone marrow aspirate will be required at all time points 
 to assess 
treatment response.  
■
For subjects who undergo a SCT, bone marrow evaluations are not required during 
the first 100 days post-SCT.  After 100 days, bone marrow evaluations should be 
performed at the next per protocol time point per the SOA.  If a subject has a bone 
marrow evaluation earlier than the next per protocol time point, then the bone marrow 
samples should be processed and submitted to the central laboratory per the central 
laboratory manual.  
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In addition to the bone marrow aspirate, a bone marrow biopsy is required at Day -4 and 
Day 28.  A bone marrow biopsy at all other time points is recommended and should be 
performed if standard of care.  Note: Anytime the bone marrow aspirate is a dry tap, then 
a bone marrow biopsy is required.  In the case of a dry tap, the bone marrow biopsy will 
be used to determine disease burden by immunohistochemical (IHC) analyses.  The 
following markers will be analyzed by IHC: CD10, CD19, CD20, CD34, Pax5 and TdT. 
For subjects who sign the optional portion of the consent form, a Day 7 bone marrow 
biopsy and aspirate will be performed.  The optional day 7 bone marrow may be 
performed between day 7 and 14.
Reminders: 
■
For subjects with a CR, collection and analysis of CSF is required to confirm CR (see 
Section 7.7)
■
For subjects with PD, a PBMC sample should be collected at time of progression and 
prior to starting subsequent anticancer therapy 
Locally evaluated % blasts from the bone marrow evaluation and if available local MRD will be 
entered to the CRF.
Overall response will be assessed by the investigator per Appendix 1.  If bone marrow blasts are 
≤ 5% and circulating blasts are ≥ 1%, then additional studies (eg, flow cytometry) should be 
performed to quantify the blasts.
Bone marrow aspirate and biopsy samples will be processed and submitted to the central 
laboratory as outlined in the central laboratory manual.  Refer to the laboratory manual for 
collection, processing and shipment requirements; note some samples, eg, MRD, must be 
shipped on the same day of collection.  Below is an overview of the sample types that will be 
required.
Samples from bone marrow aspirate may include:

MRD assessment

Stained slide smears
The same slides used to evaluate ALL disease status (eg, % blasts) locally will be 
submitted to the central laboratory and will then be returned back to the investigative site 
after the review is completed.  If the same slides used to diagnose ALL cannot be 
submitted to the central laboratory per institutional policy, then slides from the same 
procedure should be submitted.  See central laboratory manual for details.

Bone marrow mononuclear cells
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Samples from bone marrow biopsy may include:

Touch prep slide

Core biopsy in formalin, formalin-fixed paraffin embedded block, or unstained slides
The corresponding pathology report should be submitted to the central laboratory along with the 
archival and on-study bone marrow samples. 
7.9.2.
Imaging Requirements (Only Applies to Subjects with Known Non-CNS 
Extramedullary Disease at Baseline)

Extramedullary disease will be assessed prior to baseline with an imaging modality 
appropriate for the anatomical site and clinical scenario (eg, MRI for CNS lesion, ultrasound 
for testicular lesion, CT for intra-abdominal or thoracic lesion).  
For all subjects with known non-CNS extramedullary disease, images must be taken 
within 28 days before conditioning chemotherapy.  In addition, for subjects receiving 
bridging chemotherapy, images must be taken after bridging chemotherapy has 
completed. 

Following KTE-X19 infusion, the first on study images will occur at the time of first 
presumed response (ie, bone marrow blasts ≤5%)

Subsequent images will continue as per the SOA through Month 24 or disease progression, 
whichever occurs first.  If the subject’s disease has not progressed by Month 24, then images 
will be performed per standard of care until disease progression.

All on-study assessments of extramedullary disease detected through imaging should be 
made with the same imaging modality and of the same anatomical locations as imaged at 
baseline.  

Response is evaluated by the investigator (Appendix 1).  

For all subjects, images should be performed per standard of care anytime the subject
presents with symptoms suggestive of disease progression 
 
 

Images will be submitted to a central imaging vendor; central imaging vendor manual to be 
provided separately.
7.10.
Biomarkers
Biomarker analysis will be performed on blood and bone marrow derived tumor samples to 
evaluate predictive and pharmacodynamic markers for KTE-X19. Prognostic markers specific 
for B-ALL and related to the tumor immune environment may also be evaluated.
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Protocol KTE-C19-103  
Amendment 6 
 
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Protocol KTE-Cl9-103 
Amendment 6 
The presence, expansion, persistence, and immunophenotype oftransduced anti-CD19 CART 
cells will be monitored in the blood and bone maiTow b flow c omet:I . 
A pre-treatment bone maITow aspirate and biopsy will be collected for cent:I·al pathology review, 
establishment of baseline protein and molecular markers for subsequent MRD assessment and 
evaluation of ro nostic markers s ecific for B-ALL and also the tumor immune 
resence of residual leukemic blasts will be erfo1med on bone 
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KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
7.11. 
Procedures by Study Period 
Investigative sites will maintain a log of all screened subjects who were reviewed and evaluated 
for study participation. Infonnation collected on the screening log should include limited 
infonnation such as the date of screening, date the subject was enrolled or the reason for why the 
subject failed screening. 
7.11.1. 
Screening 
The screening period begins on the date the subject signs the IRB/IEC approved ICF and 
continues through enrollment. Info1med consent must be obtained before completion of any 
study specific procedures. Procedures that are pa1t of SOC are not considered study specific 
procedures and may be perfonned prior to obtaining consent and used to confom eligibility. 
Confomation of this data must occur within the time allowance as outlined below and in the 
SOA. 
After written infonned consent has been obtained, subjects will be screened to confinn study 
eligibility and pait icipation. Only subjects who meet the eligibility criteria listed in Section 5 
and who commence leukapheresis will be enrolled into the study. If at any time prior to 
enrollment the subject fails to meet the eligibility criteria, the subject should be designated as a 
screen failure on the subject screening log with the reasons for failing screening. 
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The following assessments/procedures are to be completed during the screening period at the 
time points outlined in the SOA:

Medical history (see Section 7.3)

Physical examination including height and weight (see Section 7.4)

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

ECOG performance status 

EQ-5D (Phase 2 subjects only; see Section 7.4)

Neurological assessment (see Section 7.5)

ECG (see Section 7.6)

Left ventricular ejection fraction (LVEF) and pericardial effusion assessment (ECHO) (see 
Section 7.6)

Labs (see Section 7.8)
β-HCG pregnancy test (serum or urine) on all women of child-bearing potential
Chemistry panel
CBC with differential
Peripheral blood
CD19 immunophenotyping on peripheral blood or bone marrow aspirate
Lumbar puncture for collection of CSF (see Section 7.7)
For EU sites, viral serologic tests (eg, HIV, hepatitis B, hepatitis C) will be carried out 
per institution guidelines and EU regulations. This may be done within the 30 days prior 
to leukapheresis and/or on the day of leukapheresis.

CSF prophylaxis if indicated (see Section 6.4)

Chest x-ray (not required if other imaging modalities are used for baseline assessment of 
chest)

Disease assessment (see Section 7.7 and Section 7.9)
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
Screening bone marrow evaluation:
If available, archival formalin-fixed paraffin embedded (FFPE) bone marrow block 
and/or slides used for the original diagnosis of ALL will be submitted to the central 
laboratory  
A bone marrow aspirate and biopsy is required at screening and will be performed after 
the last dose of systemic chemotherapy and within approximately 14 days before 
enrollment to establish baseline disease.  
■
If there is a delay between when the screening bone marrow is performed and the 
apheresis, contact the Kite Medical Monitor for guidance on whether or not bone 
marrow evaluation needs to be repeated.  If a fresh bone marrow aspirate and biopsy 
was recently collected and properly stored prior to consent, then contact the Kite 
Medical Monitor to confirm if this sample is adequate for screening.  

Serious Adverse Event reporting (refer to Section 9)

Concomitant medications documentation and previous cancer treatment history (see 
Section 6.7)
7.11.2.
Rescreening
Subjects who are unable to complete or fail to meet the eligibility criteria during the 28-day 
screening period will be allowed to rescreen. Subjects will retain the same subject 
indentifcation number assigned at the original screening.  If rescreening occurs within 
28 days of the signing of the original informed consent, the assessment or procedure that 
initially resulted in the subject failing screening will be performed, including any other 
procedures that fell outside of the designated screening window (ie, lab assessments); all other 
initial screening procedures/assessments do not need to be repeated.
7.11.3.
Enrollment/Leukapheresis
Before leukapheresis commences, the following criteria must be met:

In general, all eligibility criteria confirmed during screening must not be known to be 
violated prior to leukapheresis.  Additionally, the investigator must review and confirm that 
the last CBC with differential and chemistry panel drawn prior to the start of leukapheresis 
must meet the eligibility criteria detailed in Inclusion criterion 105.  If any screening 
assessments or procedures are repeated between screening and the start of leukapheresis and 
results are outside the eligibility criteria (Section 5), contact the Kite medical monitor before 
proceeding with leukapheresis.  

Subjects must have no evidence of clinically significant infection prior to leukapheresis.  
Should a subject have clinically significant infection immediately prior to leukapheresis, cell 
collection must be delayed until the event resolves.  
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KTE-C19 
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Protocol KTE-Cl9-103 
Amendment6 
• If leukapheresis is delayed beyond 5 days, a CBC with differential and chemistiy panel must 
be repeated. 
• If WBC collected at time ofleukapheresis is ~ 50,000 cells/µL a contact must be made to the 
Kite Medical Monitor before proceeding with leukapheresis. 
• 
Co1iicosteroid therapy at a phaimacologic dose (> 5 mg/day of prednisone or equivalent 
doses of other corticosteroids) and other immunosuppressive mugs must be avoided for 
7 days prior to leukapheresis (see Section 6.8). 
Once a subject commences leukapheresis, the subject will be considered emolled into the study. 
The followin 
· 
ill occur on the leukapheresis collection day 
( emollment) 
• 
Vital signs 
I 
• 
Labs (to be di·awn prior to leukapheresis either on the day of or the day before 
leukapheresis) (see Section 7.8) 
• 
Leukapheresis (see Section 6.2) 
• 
Adverse/Serious Adverse Event repo1iing (refer to Section 9) 
I 
Vitals, lab di·aws, adverse/serious adverse event repo1iing and concomitant medications 
documentation may be perfonned the day before leukapheresis, unless otherwise specified. 
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7.11.4.
Bridging Chemotherapy Period
If prescribed, bridging chemotherapy will be administered after leukapheresis and completed at 
least 7 days or 5 half-lives, whichever is shorter, prior to initiating conditioning chemotherapy
(see Section 6.3).  
The following procedures will be performed:

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature

Labs (to be drawn prior to chemotherapy) (see Section 7.8)
Chemistry Panel 
CBC with differential

Bridging chemotherapy (see Section 6.3)

Adverse/Serious Adverse Event reporting (refer to Section 9) 

Concomitant medications documentation (see Section 6.7)
Note:  As appropriate, vitals and labs should be repeated each day bridging chemotherapy is 
administered.
7.11.5.
CSF Prophylaxis Period
Intrathecal chemotherapy for CSF Prophylaxis will be administered any time during screening 
through 7 days prior to KTE-X19 infusion (see Section 6.4).  
The following procedures will be performed:

Vital signs
 

Intrathecal chemotherapy (see Section 6.4)
 
Note: As appropriate, vitals and labs should be repeated each day CSF prophylaxis is 
administered.
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 
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CCI
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7.11.6.
Conditioning Chemotherapy and KTE-X19 Infusion
Administration of KTE-X19 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 (elevated 
C-reactive protein [CRP]) are diagnoses of exclusion that require a documented workup to 
establish.  Conditioning chemotherapy and KTE-X19 infusion should only be initiated after 
it is reasonably assured that cell infusion can safely proceed.  
The investigational medicinal product (KTE-X19) must be available before initiation of 
conditioning chemotherapy.
Refer to Section 7.11.7.5 for Requirements to Work-up Potential Infectious and/or 
Inflammatory States.
7.11.6.1.
Conditioning Chemotherapy Period
7.11.6.1.1.
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 7.11.7.5 must be performed to determine the potential 
cause if there is no identified source of infection.

Temperature > 38ºC within 72 hours before conditioning chemotherapy

CRP > 100 mg/L any time between enrolment to start of conditioning chemotherapy

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 segments/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 HEENT, cardiac, vascular, respiratory, 
gastrointestinal, integumentary, and neurological systems must not reveal evidence of 
infection/inflammation.

The subject must not have received systemic anti-microbials for the treatment of a 
known or suspected infection within 48 hours before conditioning chemotherapy 
(prophylactic use of anti-microbials is allowed).  
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 


KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
• 
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 conditioning chemotherapy. 
7.11.6.2. 
Conditioning Chemotherapy Administration (Day -4 Through Day -2 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 -4. 
Subjects will initiate conditioning chemotherapy with cyclophosphamide and fludarabine 
beginning on Day -4 and through Day -2, with 1 rest day (Day -1) before receiving 
KTE-X19. The 3-day conditioning chemotherapy regimen will be administered in an 
outpatient setting. 
Conditioning chemotherapy (fludarabine and cyclophosphamide) will be supplied by the 
investigative site unless othe1wise noted and should be administered per institutional guidelines. 
Refer to the cunent product label for guidance on packaging, storage, preparation, administration 
and toxicity management associated with the administration of chemotherapy agents. 
Before conditioning chemotherapy commences, the criteria outlined in Section 7 .11.6.1 must be 
met. 
Provided the criteria for conditioning chemotherapy are met, the 3-day conditioning regimen of 
fludarabine and cyclophosphainide will be administered in accordance with the following daily 
dosing instructions: 
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KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
• 
Fludarabine 25 mg/in2/day IV in 50 mL of 0.9% sodium chloride over 30 minutes on Day-4, 
Day -3, Day -2 followed by: 
• 
Cyclophosphamide at a dose of 900 mg/m2/day IV over 60 minutes on Day -2 only 
I 
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7.11.6.3. 
Conditioning Chemotherapy Procedures 
The following procedures will be completed during Day-4 to Day -2. Day -1 is a rest day. 
• 
Vital signs including blood pressure, heart rate, oxygen saturation, and temperature 
• 
ECOG perfo1mance status 
• 
Labs (to be drawn prior to chemotherapy) (see Section 7.8) 
-
~-HCG pregnancy test (sernm or urine) on all women of child-bearing potential 
-
Chemistiy Panel 
-
CBC with differential 
Note: If subject did not have bridging therapy and hence bone man ow is not 
collected between the end of bridging chemotherapy and staii of Conditioning 
chemotherapy, then sites must assess peripheral blasts counts during this time period 
(eg, at Day -4). 
-
Blood draw for PBMCs and cytokine levels 
• 
Bone manow evaluation (see Section 7.9.1) 
-
In subjects who receive bridging chemotherapy, an additional bone man ow sample is 
required between the end of bridging chemotherapy and Day -4. If bridging 
chemotherapy is not administered, then the additional bone man ow sample is not 
required. 
• 
Conditioning chemotherapy (Fludarabine and cyclophosphamide) administl'ation (see 
Section 6.5) 
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
Adverse/Serious Adverse Event reporting (refer to Section 9)  

Concomitant medications documentation (see Section 6.7)
7.11.7.
Investigational Product Treatment Period
7.11.7.1.
Pre-KTE-X19 Infusion Criteria
If any of the following criteria are met prior to the initiation of KTE-X19, then the work-up 
listed in Section 7.11.7.5 must be performed to determine the potential cause if there is no 
identified source of infection.  

Temperature > 38°C within 72 hours of KTE-X19 infusion

CRP > 100 mg/L any time between enrollment to start of KTE-X19 infusion

WBC count or WBC differential concerning for infectious process between enrollment 
to start of KTE-X19infusion (eg, WBC > 20,000, rapidly increasing WBC, or 
differential with high percentage of segments/bands)
Additionally:

All eligibility criteria of the protocol must be met.  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, and cardiac, vascular, 
respiratory, gastrointestinal, integumentary, and neurological systems must not reveal 
evidence of infection/inflammation.

The subject must not have received systemic anti-microbials for the treatment of a 
known or suspected infection within 48 hours before KTE-X19 (prophylactic use of 
anti-microbials 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.
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 


CONFIDENTIAL
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Once the above criteria are met, then the subject can proceed with administration of 
KTE-X19.
If the KTE-X19 infusion is delayed > 2 weeks, protocol guidelines should be followed 
regarding the need for repeat conditioning chemotherapy. 
7.11.7.2.
Hospitalization for KTE-X19 Infusion
Subjects will be hospitalized to receive infusion of KTE-X19 followed by a minimum 7 day
observation period unless otherwise required by country regulatory agencies (refer to 
Appendix 3 for details).
Subjects will remain in the hospital through day 7 post infusion of KTE-X19.  Subjects should 
not be discharged from the hospital until all KTE-X19-related non-hematological toxicities 
return to grade ≤ 1 or return to baseline. Subjects may be discharged with non-critical and 
clinically stable or slowly improving toxicities (eg, renal insufficiency) even if > grade 1, if 
deemed appropriate by the investigator. Subjects should remain hospitalized for ongoing
KTE-X19-related fever, hypotension, hypoxia, or ongoing central neurological toxicity 
> grade 1, or if deemed necessary by the treating investigator.
Given the possibility that a subject could develop CRS or neurologic events in the outpatient 
setting after discharge, subjects and their family members/caregivers should be educated on 
potential symptoms of these syndromes such as fever, dyspnea, confusion, aphasia, dysphasia, 
somnolence, encephalopathy, ataxia, or tremor. If subjects develop these symptoms, they should 
be instructed to immediately contact the principal investigator or seek immediate medical 
attention. 
See Section 6.8 for excluded medications prior to and after KTE-X19.
7.11.7.3.
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 
Kite medical monitor

Acetaminophen 650 mg PO or equivalent

Diphenhydramine 12.5 mg administered either orally or via IV or equivalent
7.11.7.4.
KTE-X19 Infusion (Day 0)
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 
the IPM.  It is recommended that vital signs are recorded before KTE-X19 infusion and then 
routinely as clinically indicated (eg, fever ≥38.3°C). 
The IPM must be reviewed prior to administration of KTE-X19. 
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 


CONFIDENTIAL
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Research sites should follow institutional guidelines for the infusion of cell products.
During this period, the following procedures will be completed at the time points outlined in the 
SOA:

Vital signs including blood pressure, heart rate, oxygen saturation, and temperature every
Q4-6 hours during hospitalization (see Section 7.4 for vital sign requirements during the 
initial hospitalization)

ECOG performance status

EQ-5D (Phase 2 subjects only; see Section 7.4)

Neurological assessment (see Section 7.5)

Labs (before KTE-X19 infusion) (see Section 7.8)
Chemistry Panel
CBC with differential
Blood draw for PBMCs and cytokine levels (See SOA for frequency)
Recommended:  Monitoring of CRP, ferritin, and LDH (only if LDH is elevated at 
baseline) levels may assist with the diagnosis and define the clinical course in regards to 
CRS/neurologic events.  It is, therefore, recommended that CRP, ferritin, and LDH (if 
elevated at baseline) be monitored daily starting at Day 0 and continuing through 
hospitalization. In addition, lactate should be monitored as clinically indicated.   

Lumbar puncture for subjects with first onset grade ≥ 2 neurologic symptoms should be 
completed for examination of CSF (see Section 7.7)

As applicable, an additional cytokine sample should be drawn at the first onset and first 
reoccurrence of any ≥grade 2 CRS (per Lee 2014 criteria; Table 15) if not already collected 
on that day  

Bone marrow evaluation (see Section 7.9)
For subjects who sign the optional consent form, an additional bone marrow 
biopsy/aspirate will be collected day 7 post KTE-X19 infusion.  If sample cannot be 
collected on day 7, then sample can be collected between day 7 – 14. 

KTE-X19 pre-medications (see Section 7.11.7.3)

Infusion of KTE-X19

Adverse/Serious Adverse Event reporting (refer to Section 9 for safety reporting guidelines)

Concomitant medications documentation (see Section 6.7)
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 


CONFIDENTIAL
Page 58 of 100
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7.11.7.5.
Requirements to Work-Up Potential Infectious and/or Inflammatory States 
Prior to KTE-X19 Infusion
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 anti-microbials if clinically 
feasible): 
Blood cultures (aerobic and anaerobic x2 bottles each) and UA and urine culture.   
Deep/induced sputum culture if clinically indicated.
All indwelling lines, such as central venous catheters, should be examined for any 
signs of infection, and additional cultures should be drawn from the line.
Nasopharyngeal-throat (NPT) swab or equivalent assay for viral infection such as 
influenza A/B (including H1N1), parainfluenza 1/2/3, adenovirus, respiratory 
syncytial virus, coronavirus, metapneumovirus
Collection of fungal cultures and markers as appropriate (eg, galactomannan, 
fungitell)
Collection of appropriate serum viral studies (eg, cytomegalovirus [CMV])

If a central nervous system process is suspected, appropriate brain imaging and 
subsequent lumbar puncture with cytology, culture, Gram stain, and viral PCR should 
be performed.  

Any additional sign or symptom-directed investigation should be performed as 
clinically indicated.
Prior to proceeding with conditioning chemotherapy and/or KTE-X19 infusion, the above 
workup must not suggest the presence of an active infection, and all requirements for 
conditioning chemotherapy and/or KTE-X19 infusion must be satisfied.  If the KTE-X19 
infusion is delayed > 2 weeks following conditioning chemotherapy, protocol guidelines 
should be followed regarding the need for repeat conditioning chemotherapy. 

If the above workup was triggered due to CRP > 100 mg/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.
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 


KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
7.11.8. 
Post-treatment Assessment Period 
After completing KTE-X19 infusion and discharged from the hospital, all subjects will be 
followed in the post ti·eatment assessment period. Counting from day O (KTE-X19 infusion), 
subjects will return to the clinic at the following intervals. 
• 
Day 14 (± 2 days) 
• 
Day 28 (+ 3 days) 
• 
Week 8 (± 1 week) 
• 
Month 3 (± 2 weeks) 
Subject will allow key sponsor contacts to continue to access medical records so that infonnation 
related to subjects health condition and initial ti·eatment response may be obtained. 
The following procedures will be completed for subjects as outlined in the SOA: 
I 
I 
• 
EQ-5D (Phase 2 subjects only; see Section 7.4) 
I 
• 
Labs (see Section 7.8) 
-
Chemistry Panel 
-
Anti-KTE-X19 antibodies 
I 
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• 
Disease Assessment (see Section 7.7 and Section 7.9) 
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
Adverse/Serious Adverse Event reporting (refer to Section 9 )

Concomitant medications documentation (see Section 6.7)
Following the initial hospitalization for the KTE-X19 infusion, if the subject is hospitalized with 
any KTE-X19 related adverse event, 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
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 child-bearing potential

Proceed to the long term follow-up period (see Section 7.11.9 for details).
7.11.9.
Long-term Follow-up Period
All enrolled subjects will be followed in the long term follow-up period for survival and disease 
status if applicable. Subjects will begin the long term follow-up period after they have 
completed the Month 3 visit of the post treatment assessment period (whether they have 
responded to treatment or went straight to the month 3 visit due to disease progression) 

Every 3 months (± 2 weeks) through Month 18

Every 6 months (± 1 month) between Month 24 - Month 60

Beginning with year 6, Month 72 (± 3 months), subjects will return to the clinic 1 time 
annually up to 15 years after the last subject receives their KTE-X19 infusion.  
The following procedures will be completed for subjects who are enrolled and receive KTE-X19, 
at the time points outlined 
:

EQ-5D (Phase 2 subjects only; see Section 7.4)
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 
CCI
CCI


KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
• 
Disease assessment (see Section 7.7 and Section 7.9) 
I 
• 
Survival Status - subjects may be contacted by telephone to confom smvival status 
• 
Labs (see Section 7.8) 
I 
-
Anti-KTE-X19 antibodies 
I 
• 
Targeted Adverse/Serious Adverse Event reporting (refer to Section 9 for safety repoiting 
guidelines) 
I 
I 
Subjects who undergo an allogeneic SCT will continue to be followed in the L TFU period and 
undergo the following assessments at the timepoints outlined in the SOA: 
• 
Disease status 
• 
Survival status 
• 
Serious Adverse Event repo1iing (see Section 9.4) 
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KTE-C19 
Protocol KTE-Cl9-103 
• 
Blood draw for: 
I 
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I 
I 
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If applicable anti-KTE-X19 antibodies (see Section 7.11.9) 
Kite Phruma, Inc. 
Amendment6 
Should the subject fail to return to the clinic for a scheduled protocol specific visit, sites will 
need to make 2 attempts by a combination of telephone and mail to contact the subject. Sites 
must document both attempts to contact the subject. If a subject does not respond within 1 month 
after the second contact the subject will be considered lost to follow-up and no additional contact 
will be required. 
7.11.10. 
Retreatment 
Subjects will be pennitted to receive 1 additional KTE-X19 infusion provided the subject 
achieved remission ofleukemia (CR, CRh, or CRi) after the initial KTE-X19 infusion at ~ month 
3 disease assessment and subsequently progressed (>5% bone manow blasts or progression of 
EMD per local assessment 
CONFIDENTIAL 
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KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment6 
In addition, the subject must meet all of the following criteria: 
• 
All inclusion criteria 
-
Note: inclusion criteria 108 only applies if subject must undergo another leukapheresis in 
order to manufacture another dose ofKTE-X19 
• 
All exclusion criteria except for prior KTE-X19 use in this study 
• 
Subject must not have had a grade~ 2 KTE-X19-related immediate hypersensitivity reaction 
• 
CD19 tumor expression in bone maiTow or peripheral blood must be documented after 
progression. If CD 19 expression is quantified, then there must be 
90% CD 19 positive 
blasts. 
• 
Subject did not experience grade 4 CRS, grade 4 neurologic events, or any grade of edema in 
the brain with the first KTE-X19 infusion 
• 
Any CRS and neurologic events have fully resolved prior to the retreatment 
• 
Any toxicity related to fludai·abine or cyclophosphamide should be resolved to ::; grade 1 or 
return to baseline, prior to retreatment, with the exception of clinically insignificant toxicities 
(eg, alopecia). 
• 
The subject has not received subsequent therapy for the treatment of leukemia 
• 
The subject does not have known anti-KTE-X19 antibodies 
• 
In consultation with the Kite Medical Monitor there is agreement to give the additional 
KTE-X19 infusion 
If the rate of grade ~ 2 KTE-X19-related immediate hypersensitivity reaction to reinfusion of 
KTE-X19 is > 33% after a minimum of 6 subjects, then no additional subjects will be pennitted 
to receive an additional dose ofKTE-X19. Incidences of grade~ 2 KTE-X19-related immediate 
hypersensitivity reaction will be monitored each time a subject is retreated. In the cases when 
2 or more subjects with grade ~ 2 KTE-X19-related immediate hypersensitivity reaction have 
been observed before the 
subject is retreated, then no additional subjects will be permitted to 
receive an additional dose of KTE-X19. 
A discussion regarding benefits and risks of any additional KTE-X19 dose, including the 
potential need to undergo leukapheresis a second time for the manufacturing ofKTE-X19, 
should occur with the subject prior to perfonning any study related procedures or treatment. 
This conversation should also be recorded in the subject's source document. 
Allowance for additional doses is based on clinical experience reported in studies conducted at 
the pediatric (Lee et al, 2015) and Surge1y Branch (Kochenderfer et al 2015 of the NCI where 
6 sub· ects in total have been retreated u on ro ·ession. 
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Any subject who receives an additional dose will follow the same treatment schedule and 
procedural requirements per the initial treatment.  This includes bridging chemotherapy, CSF 
prophylaxis and conditioning chemotherapy, unless discussed with the Kite Medical Monitor.
Subjects enrolled in Phase 1 will receive the KTE-X19 dose selected for Phase 2 if they are 
retreated in Phase 2. If the Phase 2 regimen has not yet been selected, subjects will receive the 
last KTE-X19 regimen that was determined safe by the SRT or the current dose being evaluated 
in the study. Subjects enrolled in Phase 2 will receive the KTE-X19 dose at the Phase 2 dose.
KTE-C19 
Kite Pharma, Inc. 
Protocol KTE-C19-103  
Amendment 6 
 


KTE-C19 
Kite Phruma, Inc. 
Protocol KTE-Cl9-103 
Amendment 6 
Table 4. 
Schedule of Assessments 
Schedule of Assessments 
(1 of 2) Procedures 
Visit Frequency 
Vital signs 1 
Weight 
ECOG Performance Status 
Neurological Assessment 8 
EQ-SD (Phase 2 subjects only) 14 
ECG 
L VEF and PE assessment by 
ECHO 
Bone Marrow Evaluation 
(biopsy and aspirate) for 
Disease Assessment i 
Extramedullary Imaging 3 
Overall Response Assessment 
(Appendix 1) 
Leukapheresis 5 
CSF Prophylaxis 6 
Bridging Chemotherapy 6 
Conditioning Chemotherapy 
(Fludarabine & 
Cyclophosphamide) 6 
KTE-X19 infusion IV 
CONFIDENTIAL 
Screening 9 
Enrollment / 
Bridging 
CSF 
14 days 
before 
enrolhnent 
x i 
X 
X 
X 
X 
X9 
X9 
x i 
Leukapheresis 
Chemotherapy 
Prophylaxis 
~S days after 
eligibility 
confirmation 
x s 
x s 
X 
x 3 
x 6 
x 1 
x 1 
x 6 
Page 65 of 100 
Conditioning 
Chemotherapy 
Pe1iod 
.4 
-3 
-2 
-1 
X 
X 
X 
X 
x i 
X 
X 
X 
IP 
Administration 
Pe1iod 11 
0 
1 - 7 13 
x i 
x i 
X 
X 
x s 
X 
OptDay7 
Bx&Ai 
x ii 
Post Treatment Follow-up io, 11 
(each visit calculated from Day 0) 
Day 14 
(± 2 
days) 
X 
Day28 
(+ 3 
days) 
X 
X 
X 
x i 
x 3 
X 
Week8 
(± 1 
week) 
X 
x i 
x 3 
X 
Month 3 
(± 2 
weeks) 
X 
X 
X 
x i 
x 3 
X 
31 October 2018 


KTE-C19 
Protocol KTE-Cl9-103 
Schedule of Assessments 
(1 of 2) Procedures 
Visit Frequency 
Pregnancy test (serum or urine 
~-HCG) 
Screening 9 
Enrollment / 
Bridging 
CSF 
Leukapheresis 
Chemotherapy 
Prophylaxis 
14 days 
~S days after 
before 
eligibility 
enrollment 
confirmation 
X 
Footnotes for Schedule of Assessments (1 of 2) 
Conditioning 
Chemotherapy 
Pe1iod 
-4 
-3 
-2 
-1 
X 
IP 
Administration 
Pe1iod 11 
0 
1 - 7 13 
Kite Phruma, Inc. 
Amendment6 
Post Treatment Follow-up io, 11 
(each visit calculated from Day 0) 
Day 14 
Day28 
Week8 
Month3 
(±2 
(+ 3 
(± 1 
(± 2 
days) 
days) 
week) 
weeks) 
X 
1 
Vital signs: Includes blood pressure, heart rate, oxygen saturation, and temperature. Height will be collected at screening. Vitals will be monitored before and after the KTE-X19 
infusion and then routinely (every 4-6 hours) while hospitalized. If the subject has a fever (temperature 38.3oC or greater) at any time during hospitalization, vital signs will be 
monitored more frequently as clinically indicated. 
2 
Bone Marrow Evaluation (biopsy and aspirate) for Disease Assessment (Section 7.9): For screening bone marrow evaluation see section 7.9.1. A bone marrow aspirate will be 
required at all timepoints per the SOA table above (Subjects that receive an SCT, bone marrow evaluations are not required for the first 100 days post SCT). In addition to the 
bone marrow aspirate, a bone marrow biopsy is required at Screening, Day -4 and Day 28. The Day -4 bone marrow biopsy is only required for subjects receiving bridging 
chemotherapy. A bone marrow biopsy at all other timepoints is recommended and should be performed if standard of care. Anytime the bone marrow aspirate is a dry tap, then a bone 
marrow biopsy is required. Disease status will be evaluated per institutional practices. A portion of the aspirate collected will be submitted to the central lab on the day of collection 
and analyzed for MRD; see the central laboratory manual for details. The optional day 7 bone marrow biopsy and aspirate may be performed between day 7 and 14. Overall response 
will be assessed by the investigator per Appendix 1. If bone marrow blasts are~ S% and circulating blasts are,:: 1 %, then additional studies (eg, flow cytometry) should be performed 
to quantify the blasts. 
3 
Extramedullary Imaging (Section 7.9.2): For subjects with known baseline extramedullary disease detected through imaging, baseline images appropriate for the anatomical location 
and clinical scenario will be performed. For subjects receiving bridging cliemotherapy, images will be performed after bridging chemotherapy and before conditioning chemotherapy. 
For subjects not receiving bridging chemotherapy, images will be performed within 28 days before conditioning cliemotherapy. On study images will be performed with the same 
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4 
s 
I 
7 
imaging modality and anatomical location as imaged at baseline. Following KTE-X19 infusion, the first on study images will occur at the first occurrence of leukemia remission based 
on the bone marrow evaluation. Subsequent images will continue as per the SOA through Month 24 or disease progression, whichever occurs first. If the subject's disease has not 
progressed by Month 24, then images will be performed per standard of care until disease progression. For subjects with or without extramedullary disease, images should be performed 
per standard of care anytime the subject presents with symptoms suggestive of disease progression. 
Lumbar Puncture (Section 7. 7): CSF samples will be analyzed locally for disease assessment and centrally for disease assessment and toxicity evaluation at the following timepoints: 
1) Baseline - a CSF result obtained within 30 days before enrollment will be acceptable eligibility determination, 2) at the time ofCSF prophylaxis, 3) for subjects with baseline CNS-2 
disease, a CSF sample is required at the time of first presumed response based on bone marrow (bone marrow <5%), 4) first onset of grade 2 or greater neurological symptoms or as 
medically indicated S) for subjects with a CR, collection and analysis of CSF is required to confir m CR and 6) per institutional standard of care. Should a subject have an Ommaya 
reservoir and there is no evidence of blockage of CSF flow from the spinal canal, withdrawal of the CSF sample though the reservoir is acceptable. CSF samples (ie, collected on or 
after informed consent) will be submitted to the central laboratory. 
Leukapheresis (Sections 6.2 and 7.11.3): All leukapheresis criteria must be met before leukapheresis commences. Vitals, weight, and laboratory sample draws may be 
da of 01· before leuka heresis, exc t wei t must be collected on da of leuka heresis. All laborato sam les should be drawn before the leuka heresis rocedure. 
(Section 6.3) will be administered after leukapheresis and completed at least 7 days or 5 half-lives, whichever is shorter, prior to initiating 
con tiorung c emo erapy. CSF prophylaxis (Section 6.4) will be administered any time during screening through 7 days before the KTE-X19 infusion. Subjects who are enrolled 
with CNS-2 disease at baseline must receive CSF prophylaxis after leukapheresis and at least 7 days prior to KTE-X19, unless otherwise approved by the Kite Medical Monitor. 
Multiple doses of CSF prophylaxis can be given per investigator discretion in accordance with institutional guidelines, but at least 7 days must pass between the last dose of CSF 
prophylaxis and KTE-X19. Should a subject have an Ommaya reservoir and there is no evidence of blockage of CSF flow from the spinal canal, administration of CSF prophylaxis 
through the reservoir is acceptable. Conditioning chemotherapy (Section 6.5) consisting offludarabine on Day-4, -3, -2 prior to KTE-X19 and cyclophosphamide on Day -2 prior to 
KTE-X19 will be administered. 
Vitals, Chem panel, and CBC: collected each day prior to CSF prophylaxis and bridging chemotherapy (see Section 7.11.4 and 7.11.S). CBC 5-part preferred, but 3-part will be 
acceptable. Pe1ipheral blood : Peripheral blood will be collected at screening, and if the subject did not have bridging therapy than pe1ipheral blood will be collected during day 
-4 and submitted to the central lab. 
8 
Neurological assessment: 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. 
9 
Screening procedures (Section 7.11.1): Procedures should be performed within 14 days of enrollment (unless otherwise specified). ECG: must be performed within 30 days prior to 
enrollment; ECHO: If the last chemotherapy regimen the subject received is not considered cardiotoxic, then an ECHO performed within 28 days prior to signing the consent may be 
used for eligibility. If the last chemotherapy regimen the subject received is considered cardiotoxic, then an ECHO performed following the subjects last chemotherapy treatment and 
within 28 days prior to signing the consent may be used for confirmation of eligibility. CD19: Local CD19 immunophenotyping will be performed at screening on peripheral blood or 
bone marrow aspirate. Surface CD19 expression should be measured by flow cytometry; IHC analysis is allowed if the bone marrow aspirate is a dry tap, inadequate or there were 
insufficient circulating blasts for flow cytometry. Procedures that are part of SOC are not considered study specific procedures and may be performed prior to obtaining consent and 
used to confirm eligibility provided they are performed within the time allowance as outlined in the SOA. 
10 
If the sub·ect ro ·essions before Month 3: Refer to section 7.11.8 for the rocedures that are to be com leted. 
I 
12 
KTE-Xl 9 pre-medications: Su ~ects w 
receive acetanunop en an 
1p e ydraniine (equivalent) approximately 1 hour prior to KTE-X19 (see Section 7.11.7.3). 
13 
Please refer to Appendix 3 for requil'ements by country regulatory agencies 
14 
EQ-SD: The EQ-SD will be completed prior to other study related procedures or assessments. 
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KTE-C19 
Protocol KTE-Cl9-103 
Schedule of Assessments 
(2 of 2) Procedures 
Visit Frequency 
EQ-SD (Phase 2 subjects only) 
Bone Marrow Evaluation (biopsy and aspirate) 
for Disease assessment 1 
Month 
Month 
6 
9 
X 
X 
X 
X 
Month 
Month 
Month 
12 
15 
18 
X 
X 
X 
X 
X 
X 
Kite Phruma, Inc. 
Amendment6 
Long Term Follow-up Period 8 
(Each visit calculated from Day 0) 
Month 72 and 
Month 
Month 
Month 
Month 
Month 
Month 
Month 
Annually Up to 
24 
30 
36 
42 
48 
54 
60 
15 Years 
X 
X 
====================== 
Overall Response Assessment (Appendix 1) 
X 
X 
X 
X 
X 
X 
Survival Status 4• 7• 8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
I 
Bone Marrow Evaluation (biopsy and aspirnte) for Disease Assessment (Section 7.9.1): A bone marrow biopsy and aspirate will be performed per the SOA through Month 24 or 
r 
until disease progression, whichever occurs first. Disease status will be evaluated per institutional practices. The slides used for the local evaluation of% blasts should be submitted to 
the central laboratory along with the corresponding pathology report. If the subject's disease has not progressed by Month 24, then after Month 24 bone marrow evaluation will be 
erformed er SOC. 
3 
y samp e co ection m ong-term o ow-up, re er to Section 7 .11.9 or 
ta s. 
4 
AE/SAE reporting (Sections 9.2 and 9.4): AEs: After 3 months, only targeted adverse events will be reported in the CRF through 24 months after KTE-X19 infusion or disease 
progression, whichever occurs first. SAEs: After 3 months, only targeted serious adverse events (including targeted grade 5 serious adverse events) will be reported through 24 months 
after KTE-X19 infusion or disease progression, whichever occurs first, within 24 hours using the SAE Report Form and in the CRF. Targeted adverse events include central 
neurological, hematological, infections, GVHD, autoinmmne disorders, and secondary malignancies. Subjects who receive an allogeneic SCT will only be followed for KTE-Xl9 
related serious adverse events. Reporting of these SAEs will commence at the time the SCT preparative regimen commences through 24 months after KTE-X19 infusion or disease 
progression, whichever occurs first, within 24 hours using the SAE Report Form and in the CRF. In addition to the above SAE reporting requirements, anytime a KTE-Xl9 related 
serious adverse event occurs it will bere 
within 24 hours usin the SAE Re rt Form and in the CRF. All deaths that occurfromICF throu 
end of stud will be re rted in the CRF. 
I' 
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8.
SUBJECT WITHDRAWAL
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the physician or at the institution.
Subjects can decline to continue to receive study required treatment and/or other protocol 
required procedures at any time during the study but continue to participate in 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 investigational product, study treatment or other 
protocol required therapies and must discuss options for continued participation, completion of 
procedures and the associated data collection as outlined in the SOA. The level of follow-up and 
method of communication should also be discussed between the research staff and the subject 
and documented in the source documents.
Withdraw of full consent for a study means that the subject does not wish to receive further 
protocol required therapy or undergo procedures and the subject does not wish to continue 
further study follow-up. Subject data collected up to withdraw of consent will be retained and
included in the analysis of the study, and where permitted by local regulations, publically
available data (death records) can be included after withdrawal of consent. The investigator is to 
discuss with the subject appropriate procedures for withdrawal from the study.
As part of the study sites may be asked to conduct searches of public records, such as those 
establishing survival status, if available, to obtain survival data for any subject for whom the 
survival status is not known. Sites may be also asked to also retrieve autopsy reports to confirm 
status of disease at the time of death. 
The investigator and/or sponsor can also decide to withdraw a subject from the investigational 
product and/or other protocol-required therapies, protocol procedures, or the study as a whole or 
at any time prior to study completion.
8.1.
Reasons for Removal from Treatment
Reasons for removal from protocol required investigational products or procedures include any 
of the following:

Adverse Event

Subject request

Product not available

Lost to Follow-up

Death

Decision by sponsor
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8.2.
Reasons for Removal from Study
Reasons for removal of a subject from the study are as follows:

Subject withdrawal of consent from further follow-up

Investigator decision

Lost to follow-up 

Death
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9.
SAFETY REPORTING
9.1.
Adverse Events
An adverse event 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 adverse events observed by the investigator or reported by the 
subject are recorded in the subject’s medical record. 
The definition of adverse events 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 adverse event.
Interventions for pretreatment conditions (such as elective cosmetic surgery) or medical 
procedures that were planned before study participation are not considered adverse events.
Hospitalization for study treatment infusions or precautionary measures per institutional policy 
are not considered adverse events.
The term “disease progression” or any relapse after a remission should not be reported as adverse 
events. Death due to disease progression in the absence of signs and symptoms of underlying 
disease should be reported as the primary tumor type (eg, B-cell type acute leukemia).
For situations when an adverse event or serious adverse event is due to the disease under 
investigation report the signs and symptoms. Worsening of signs and symptoms of the 
malignancy under study should also be reported as adverse events in the appropriate section of 
the CRF. 
The investigators clinical judgment is used to determine whether a subject is to be removed from 
treatment due to an adverse event. In the event a subject requests to withdraw from protocol 
required therapies or the study due to an adverse event, the subject should undergo the 
procedures outlined in the Month 3 visit of the SOA. 
9.1.1.
Diagnosis Versus Signs and Symptoms
For adverse events, a diagnosis (if known) rather than individual signs and symptoms 
should be recorded on the AE form.  The exception is for CRS where both the diagnosis 
and signs and symptoms will be captured on the CRF AE form.  For signs and symptoms of 
the underlying cancer, the signs and symptoms should be captured.  However, on the AE 
form, the investigator should state that these signs and symptoms are due to the underlying 
disease.
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9.1.2.
Abnormal Vital Sign Values
Not all vital sign abnormalities qualify as an adverse event.  A vital sign result must be 
reported as an adverse event if it is a change from baseline and meets any of the following 
criteria:

Accompanied by clinical symptoms

Results in a medical intervention or a change in concomitant therapy

Clinically significant in the investigator’s judgment
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 adverse event.  However, if a clinically significant vital sign abnormality is a 
sign of a disease or syndrome (eg, high blood pressure), only the diagnosis (ie, 
hypertension) should be recorded on the CRF.
9.1.3.
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 adverse event 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 in Table 5:
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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, bridging chemotherapy, conditioning 
chemotherapy) or until initiation of a new anti-
cancer 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 SAEs.
Abbreviations:  GVHD, graft-versus-host-disease.
See Section 9.5 for reporting requirements.  
See Section 6.7 for targeted concomitant medications and Section 9.5 for targeted SAEs reporting requirements.
See Section 9.5 for reporting requirement for non-serious CRS events Grade ≥ 3.
The investigator must address the below AEs: 

Adverse event diagnosis or syndrome (if not known, signs or symptoms)

Dates of onset and resolution

Severity

Assessment of relatedness to investigational product, chemotherapy or study procedures

Action taken
Adverse event grading scale used will be the NCI Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.03. A copy of the grading scale can be downloaded from the CTEP 
home page (http://ctep.cancer.gov). Cytokine Release Syndrome events will also be reported 
using the grading scale outlined in the KTE-X19 IB. 
In reviewing adverse events, investigators must assess whether the adverse event is possibly 
related to 1) leukapheresis, 2) bridging chemotherapy, 3) CSF prophylaxis, 4) Conditioning
chemotherapy, 5) the investigational product (KTE-X19), or any protocol required study 
procedure. The relationship is indicated by a yes or no response and entered into the CRF. A 
yes response should indicate that there is evidence to suggest a causal relationship between the 
study treatment or procedure and the adverse event. Additional relevant data with respect to 
describing the adverse event will be collected in the CRFs.
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The investigator is expected to follow reported adverse events until stabilization or resolution.  If 
a subject begins a new anti-cancer therapy, the AE reporting period for non-SAEs ends at 
the time the new treatment is started.
9.3.
Definition of Serious Adverse Events
A 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
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. 

Results in persistent or significant disability/incapacity

Congenital anomaly/birth defect

Other medically important serious event
If an investigator considers an event to be clinically important, but it does not meet any of 
the serious criteria, the event could be classified as an SAE with the criterion of “other 
medically important serious event.” 

The terms “severe” and “serious” are not synonymous.  Severity refers to the intensity 
of an adverse event according to NCI CTCAE criteria; the event itself may be of 
relatively minor medical significance and, therefore, may not meet the seriousness 
criteria.  Severity and seriousness need to be independently assessed for each adverse 
event recorded on the CRF.

Progression of the malignancy during the study should not be reported as a AE. However, 
signs and sympotms of disease progression may be recorded as AEs or SAEs and 
indicated as being due to disease progression in the CRF.  If the malignancy has a fatal 
outcome before the end of the SAE reporting period, the the event leading to the death 
must be recorded as an SAE with the outcome of being fatal. 
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9.3.1.
Hospitalization and Prolonged Hospitalization
Any adverse event that results in hospitalization or prolonged hospitalization should be 
documented and reported as a SAE as described in Section 9.5.  
The following hospitalization scenarios are not considered to be SAEs:

Hospitalization for palliative care or hospice care

Planned hospitalization required by the protocol (eg, for monitoring of the subject or to 
perform an efficacy measurement for the study)

Planned hospitalization for a pre-existing condition

Hospitalization due to progression of the underlying cancer
9.4.
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.  Every effort should 
be made to capture the established cause of death, which may become available later on 
(eg, after autopsy).
9.5.
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 Table 6 below, all SAEs will be reported within 
24 hours and recorded in the CRF.
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Table 6.
Reporting Requirements for Serious Adverse Events
Subjects who are screen-fails or who 
are enrolled, but do not receive KITE-
X19 infusion
Subjects who are enrolled and receive KITE-X19 infusion

SAEs that occur from signing of 
the latest informed consent form 
through 30 days after the last study 
specific procedure (eg, screening 
procedure, leukapheresis, bridging 
therapy, conditioning 
chemotherapy) or until initiation of 
a new anti-cancer therapy, 
whichever occurs first, will be 
recorded in the CRF   

All SAEs that occur from signing of the screening informed consent 
form through 3 months after the KITE-X19 infusion or until 
initiation of another anti-cancer therapy, whichever occurs first

After 3 months, only targeted SAEs will be reported through 
24 months after KITE-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 SAEs.  Reporting of these SAEs will commence at 
the time the SCT preparative regimen commences through 
24 months after KTE-X19 infusion or disease progression, 
whichever occurs first, within 24 hours using the SAE Report Form 
and in the CRF.

All SAEs deemed related to KITE-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
Abbreviations:  SAE, serious adverse event; GVHD, graft-versus-host-disease; CRF, case report form; ICF, informed consent form.
See Section 6.8 for concomitant medication and Section 9.2 for targeted AE reporting requirements.
All SAEs must be submitted to Kite via email to 
 within 24 hours 
following the investigator’s knowledge of the event and using a SAE report form.
Subsequently, all SAEs will be reported to the health authorities per local reporting guidelines.
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 child bearing potential must 
have a negative pregnancy test prior to enrollment because of the potentially dangerous effects of 
the preparative chemotherapy on the fetus.  Women of childbearing potential should be 
monitored according to local and country-specific regulations.  This experimental therapy 
should not be administered to pregnant women or women who are breastfeeding.
Female subjects and female partners of male subjects are recommended to use highly 
effective contraception (method must achieve an annual failure rate of < 1%) for at least 
6 months after conditioning chemotherapy dosing.  Male subjects are recommended to not
father a child for 6 months after the conditioning chemotherapy dosing.
If a pregnancy occurs in a female subject enrolled into the study, or a female partner of a male 
subject within 6 months of completing the KTE-X19 infusion, the pregnancy must be reported to
the key sponsor contact.  Information regarding the pregnancy and/or the outcome may be 
requested by the key sponsor.
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In addition to reporting any pregnancies occurring during the study, investigators should monitor 
for pregnancies that occur after the last dose of conditioning chemotherapy through 6 months 
for female subjects and for 6 months for the female partner of the male subjects.
The pregnancy should be reported to the key sponsor contact within 24 hours of the investigators 
knowledge of the pregnancy event. 
If a lactation case occurs while the female subject is taking protocol required therapies report the 
lactation case to the key sponsor contact.
In addition to reporting a lactation case during the study, investigators should monitor for 
lactation cases that occur after the last dose of protocol required therapies through 6 months.
Any lactation case should be reported to the key sponsor contact within 24 hours of the 
investigator’s knowledge of the event.
9.7.
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 from the first 3-12 subjects 
treated with KTE-X19 and make recommendations on further study conduct and progression of 
the study based on the incidence of KTE-X19 DLT and review of serious adverse events.
Dose-limiting toxicity is defined as the following KTE-X19-related events with onset within the 
first 28 days following KTE-X19 infusion:

Grade 4 hematologic toxicity lasting more than 30 days (except lymphopenia) if not 
attributable to underlying disease

All KTE-X19-related grade 3 non-hematologic toxicities lasting for > 7 days and all 
KTE-X19-related grade 4 non-hematologic toxicities regardless of duration are considered 
DLTs, with the exception of the following which are not considered DLTs:
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
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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
CRS will be graded according to a revised grading system (Lee et al, 2014).  Adverse events 
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.
Three subjects will initially be enrolled to evaluate the safety of the KTE-X19 regimen.  Subjects 
will be evaluated for DLTs within the first 28 days following the completion of the KTE-X19
infusion.  The analysis of DLTs will be based on the DLT evaluable set as defined in 
Section 10.5.  The SRT will make recommendations based on the incidence of DLT and overall 
safety profile of the KTE-X19 regimen as outlined below:

If the subject incidence of DLT is 0 of 3 subjects, the SRT may recommend either
proceeding to Phase 2 at 2 x 106 anti-CD19 CAR T cells/kg; or 
accrual of additional subjects in Phase 1 to further characterize risk/benefit prior to 
Phase 2

If the subject incidence of DLT is 1 of 3 subjects, the SRT may recommend either
accrual of an additional 3 subjects at the same cell dose with re-evaluation of the 
incidence of DLT after a total of 6 subjects in the DLT evaluable set have been assessed 
for DLT.  In this case, the SRT may recommend accrual to Phase 2 if the cumulative 
incidence of DLT in the 6 subjects is ≤1 of 6 subjects; or 
evaluation of a lower dose of 1 x 106 anti-CD19 CAR T cells/kg in an additional set of 
3-6 subjects.  In this case, the SRT may recommend accrual to Phase 2 if the cumulative 
incidence of DLT is < 33%.

If the subject incidence of DLT is ≥ 2 of 3 subjects, a lower dose of 1 x 106 anti-CD19 CAR
T cells/kg in an additional set of 3-6 subjects will be explored.  In this case, the SRT may 
recommend accrual to Phase 2 if the cumulative incidence of DLT is < 33%.
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If the conditioning chemotherapy regimen and KTE-X19 dose evaluated in Phase 1 is 
determined to be safe based on the incidence of DLT, up to approximately 40 additional subjects 
(high and non-high burden disease) may be enrolled at 2 x 106 anti-CD19 CAR T cells/kg,
1 x 106 anti-CD19 CAR T cells/kg, or 0.5 x 106 anti-CD19 CAR T cells/kg prior to commencing 
Phase 2. The data from these additional subjects will be reviewed by the SRT who will provide 
recommendations for dose for Phase 2.  Further details to be outlined in the SRT Charter.
Based on the review of all available safety and efficacy data, the benefit/risk  ratio was 
considered most favorable  at the dose of 1 x 106 anti-CD19 CAR T cells/kg, therefore the 
dose of 1 x 106 anti-CD19 CAR T cells/kg was considered the recommended Phase 2 dose. 
The final decision to commence Phase 2 and the dose selected for Phase 2 was formally 
communicated to participating sites in a separate communication.
9.8.
Data Safety Monitoring Board
An independent Data Safety Monitoring Board (DSMB) will be chartered to review safety data 
to make trial conduct recommendations. The DSMB will review safety data in an interim 
analysis during the Phase 2 portion of the study.  For this interim analysis, the DSMB will 
review safety data after 20 Phase 2 subjects have been treated with KTE-X19 and had the 
opportunity to be followed for 30 days after the KTE-X19 infusion.  During Phase 2, Kite 
Pharma or delegate will submit SAEs or suspected unexpected serious adverse reactions 
(SUSARs) to the DSMB chair for risk benefit analysis. The DSMB Chair will review reported 
SAEs at least monthly and SUSARs as soon as received.  .  
9.9.
Criteria to Pause Enrollment
Study enrollment will be paused in Phase 1 (DLT Evaluation Period) following any grade 5 
adverse event that occurs within 30 days of KTE-X19 dosing regardless of attributions.  The 
DLT evaluation period is now complete (see Section 2.8).
As part of its oversight of the study, the DSMB also will assess criteria to pause enrollment in 
Phase 2 after 10, 20, and 35 subjects enrolled in Phase 2 have been treated with KTE-X19 and
have had the opportunity to be followed for 30 days.  Enrollment will be paused if any of the 
following is met:
Subject incidence of the following grade 4 KTE-X19-related adverse events lasting more than 
7 days is >33%:

Neurologic events

CRS (per Lee 2014 criteria)

Other non-hematological serious adverse event

Infection (treatment-related)
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10.
STATISTICAL CONSIDERATIONS
10.1.
Hypothesis
This study is designed to differentiate between a treatment that has a true overall complete 
remission rate of 40% or less and a treatment with a true overall complete remission rate of 65% 
or more. The hypothesis is that the overall complete remission rate to KTE-X19 is significantly 
greater than 40%.
A secondary endpoint, Minimum Residual Disease (MRD) Negative Rate, will be tested against 
a MRD-negative rate of 30% if the testing of the overall complete remission rate is significant.
The hypothesis is that the MRD-negative rate to KTE-X19 is significantly greater than 30%.
10.2.
Study Endpoints
10.2.1.
Primary
Phase 1: Incidence of adverse events defined as dose-limiting toxicities (DLT)
Phase 2:  Overall complete remission rate (CR + CRi) per independent review (Appendix 1).  All 
subjects that do not meet the criteria for CR or CRi by the analysis data cutoff date will be 
considered non-responders for the overall complete remission rate evaluation.
10.2.2.
Secondary

Duration of Remission (DOR): for subjects who experience CR or CRi per independent
review, DOR is defined as the time between their first complete response per indepedent
review to relapse or any death in the absence of documented relapse.  Relapse is defined in 
Appendix 1.  Subjects who do not meet the criteria for relapse and who have not died will be 
censored at the last evaluable disease assessment or disease status follow up assessment. A 
sensitivity analysis will be conducted in which non-disease mortality will be considered a 
competing risk.  Disease assessments obtained after new anti-cancer therapies (including 
allogeneic SCT) will not contribute to the derivation of duration of remission. The DOR for 
subjects that undergo allogeneic SCT while in remission is censored at the date of the 
allogeneic SCT; the DOR for subjects that undergo other new anti-cancer therapies in the 
absence of documented relapse is censored at the last evaluable disease assessment prior to 
the new anti-cancer therapies.  

In subjects who achieve CR, a TKI may be resumed 2 months after KTE-X19 infusion.  In 
such subjects who resume TKI therapy, disease assessments obtained after resumption of 
TKI therapy will contribute to the derivation of the duration of remission.  A sensitivity 
analysis will be conducted in which the duration of remission in such subjects is censored at 
the first date of the resumption of TKI therapy.
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
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 (see 
Section 7.10).  

Overall complete remission rate (CR + CRi) per investigator assessment (Appendix 1).

Allogeneic Stem Cell Transplant (Allogeneic SCT) Rate

Overall Survival: OS is defined as the time from 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 their last contact date.

Relapse-free Survival (RFS):  RFS is defined as the time from the KTE-X19 infusion date to 
the date of disease relapse or death from any cause. Subjects not meeting the criteria for 
relapse by the analysis data cutoff date will be censored at their last evaluable disease 
assessment date. Subjects who have not achieved a complete remission (CR or CRi) at the 
analysis data cutoff will be evaluated as having an RFS event at Day 0. 

Incidence of adverse events and CTCAE grade changes in safety laboratory values.

Incidence of anti-KTE-X19 antibodies.

Changes over time in the EQ-5D scale score and EQ-5D VAS score
10.2.3.
Exploratory Endpoints

Treatment related mortality rate 100 days post allogeneic stem cell transplant 
(TRM-Allogeneic SCT 100 day survival)Overall survival from the time of allogeneic stem 
cell transplant (OS-Allogeneic SCT):  OS-Allogeneic SCT is evaluated in subjects who 
undergo allogeneic SCT and is defined as the time from allogeneic SCT to the date of death.  
Subjects who have not died by the analysis data cutoff date will be censored at their last 
contact date.

Complete Remission with partial Hematological Recovery (CRh). The incidence of a CRh
(see Appendix 1 for definition).  All subjects that do not meet the criteria for CRh by the 
analysis data cutoff date will not be considered to have CRh.  

Blast-free hypoplastic or aplastic bone marrow rate:  The incidence of blast-free hypoplastic 
or aplastic bone marrow (see Appendix 1 for definition).  All subjects who do not meet the 
criteria for blast-free hypoplastic or aplastic bone marrow by the analysis date cutoff date 
will not be considered to have blast-free hypoplastic or aplastic bone marrow.

Partial remission (PR) rate:  The incidence of PR (see Appendix 1 for definition).  All 
subjects that do not meet the criteria for PR by the analysis data cutoff date will not be 
considered to have PR.
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
The overall complete remission rate (CR and CRi), MRD-negative rate, and DOR among 
subjects retreated with KTE-X19 (Section 7.11.10)

Level and activity of CAR+ T cells, as well presence CD19+ cells in blood and bone marrow.

Levels of cytokines in serum and CSF.
10.2.4.
Covariates
The primary endpoints and selected secondary endpoints will be evaluated in subgroup analysis 
by subjects with or without prior blinatumomab, and by subjects with or without prior 
inotuzumab. Such subgroup analyses may not be performed if too few (eg, n < 5) subjects in the 
mITT set have received prior blinatumomab or prior inotuzumab at the time of the analysis. 
Additional covariates and subgroup analyses will be outlined in the Statistical Analysis Plan.
10.3.
Sample Size Considerations
The anticipated enrollment in this study is approximately 100 subjects.
The primary efficacy endpoint and all analyses based on the response will be based on a mITT 
population consisting of all subjects who receive any dose of KTE-X19 in Phase 2.  
This study uses a single-arm design to test for an improvement in overall complete remission 
rate.  For the test of efficacy this study has approximately 93% power to distinguish between an 
active therapy with a 65% true overall complete remission rate from a therapy with an overall 
complete remission rate of 40% or less with a 1-sided alpha level of 0.025. A step-down test of 
the secondary endpoint MRD-negative Rate will be performed against a MRD-negative rate of 
30% if the testing of the overall complete remission rate is significant. 
In Phase 1, the SRT will review safety data after 3 subjects in the DLT evaluable set (see 
Section 10.5) have had the opportunity to be followed for 28 days after the KTE-X19 infusion.  
If the conditioning regimen and KTE-X19 dose evaluated in Phase 1 is determined to be safe 
based on the incidence of DLT, up to approximately 30 additional subjects may be enrolled to 
further evaluate safety prior to commencing Phase 2. 
During Phase 2, one interim and one primary analyses will be performed.  The interim analysis is 
for safety only and will occur after 20 subjects have been treated with KTE-X19 and have had 
the opportunity to be followed for 30 days after the KTE-X19 infusion.     The primary analysis 
will occur when the overall study enrollment is complete and all subject in the mITT set have 
had the opportunity to complete the month 6 disease assessment. 65% Approximately
100 subjects may be enrolled into the entire study. At the time of the primary analysis, in the 
event that either less than or more than 50 subjects are eligible for the mITT set, all mITT 
eligible subjects will be included in the analysis.  
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10.4.
Statistical Assumptions
This study assumes that the underlying overall complete remission rate (in the absence of 
treatment with investigational therapy) is 40%. For MRD- rate, it is assumed that the underlying 
response rate (in the absence of treatment with investigational therapy) is 30%.
10.5.
Analysis Subsets  
KTE-X19 will be administered as a single infusion at a target dose of 2 x 106 anti-CD19 CAR T 
cells/kg or 1 x 106 anti-CD19 CAR T cells/kg or 0.5 x 106 anti-CD19 CAR T cells/kg .  For 
subjects weighing greater than 100 kg, a maximum flat dose of 2 x 108 or 1 x 108 or 0.5 x 108
anti-CD19 CAR T cells/kg may be administered.  Full Analysis Set:  the full analysis set will 
consist of all enrolled subjects and will be used for summaries of subject disposition.
Modified Intention-to-treat Set (mITT):  the modified intention-to-treat set will consist of all 
subjects enrolled in Phase 2 and treated with KTE-X19.  The mITT analysis set will be used for 
all efficacy analyses unless otherwise specified.
DLT-evaluable set: All Phase 1 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 a dose level has been 
evaluated for DLT and deemed safe.  Additional Phase 1 subjects enrolled and treated 
subsequently for the purpose 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 set is defined as all subjects treated with any dose of KTE-X19.
10.6.
Access to Individual Subject Treatment Assignments
This is a single arm, open-label study and subjects and investigators will be aware of treatment 
received. Data handling procedures will be devised to reduce potential sources of bias and 
maintain the validity and credibility of the study. These procedures will be outlined in the study 
statistical analysis plan, DSMB charter, and Trial Integrity Document.
10.7.
Interim Analysis
During Phase 1, the SRT will review safety data after 3 DLT evaluable subjects 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 as 
outlined in Section 9.6.
During Phase 2, the DSMB will review safety data after 20 Phase 2 subjects have been treated 
and followed for 30 days. The DSMB will also review SAEs on a monthly basis prior to the 
primary analysis. The DSMB may request additional safety data or modifying the study conduct.
The sponsor may request additional reviews by the DSMB if safety concerns are identified. Data 
submitted to the DSMB may not have undergone completion of data cleaning procedures in 
order to facilitate timelines for DSMB review.
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10.8.
Planned Method of Analysis
The primary efficacy analysis will be performed when all subject in the mITT set have had the 
opportunity to complete the month 6 disease assessment. Additional analyses may occur after 
the primary analysis has been completed.  These additional analyses will be descriptive and will 
occur after inferential testing has been performed.  The final analysis will occur when all subjects 
have completed the study.  
10.8.1.
Overall Complete Remission Rate
The incidence of response and exact 2-sided 95% confidence intervals will be generated.  An 
exact binomial test will be used to compare the observed response rate to a response rate of 40%.
10.8.2.
Duration of Remission
Duration of Remission (DOR): for subjects who experience CR or CRi per independent review, 
DOR is defined as the time between their first complete response per independent review to 
relapse or any death in the absence of documented relapse.  Relapse is defined in Appendix 1.  
Subjects who do not meet the criteria for relapse and who have not died will be censored at the 
last evaluable disease assessment or disease status follow up assessment. Disease assessments 
obtained after new anti-cancer therapies (including allogeneic SCT) will not contribute to the 
derivation of duration of remission. The DOR for subjects that undergo allogeneic SCT while in 
remission is censored at the date of the allogeneic SCT; the DOR for subjects that undergo other 
new anti-cancer therapies in the absence of relapse is censored at the last evaluable disease 
assessment prior to the new anti-cancer therapies.  Kaplan-Meier estimates and 2-sided 95% 
confidence intervals will be generated for DOR.  Estimates of the proportion of subjects 
remained as in complete remission at 3-month intervals will be provided.
A sensitivity analysis of DOR will be conducted in which non-disease mortality will be 
considered a competing risk. A competing-risk analysis method (Klein and Moeschberger 2005; 
Putter et al, 2007) will be used to estimate the cumulative incidence of relapse.  The cumulative 
incidence of relapse in the presence non-disease related mortality (the competing risk) will be 
estimated along with 2-sided 95% confidence intervals at 3-monthly time intervals.  
10.8.3.
MRD-negative rate
The incidence of MRD-negative rate and exact 2-sided 95% confidence intervals will be 
generated.  If the statistical testing of the primary endpoint (overall complete remission rate) is 
significant, an exact binomial test will be used to compare the observed MRD-negative rate to a 
rate of 30% at a one-sided alpha level of 0.025.
10.8.4.
CR Rate, CRi Rate, and DOR to Treatment Among Subjects Retreated with 
KTE-X19 for Progressive Disease after Initial Remission
The incidence of CR rate, and CRi rate, and exact 2-sided 95% confidence intervals will be 
generated.
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DOR to retreatment is defined only for subjects who experience a CR or CRi to retreatment and 
is the time from the first complete remission after retreatment to relapse after retreatment or 
death due to disease relapse. The competing-risk analysis method will be used to estimate the 
cumulative incidence of relapse after retreatment.
10.8.5.
Overall Survival
Kaplan-Meier estimates and 2-sided 95% confidence intervals will be generated for OS.  
Estimates of the proportion of subjects alive at 3-month intervals will be provided.
10.8.6.
Allogeneic Stem Cell Transplant Rate
The incidence of Allogeneic SCT in the mITT set and 2-sided 95% confidence intervals will be 
generated.
10.8.7.
Safety
Subject incidence rates of adverse events including all, serious, fatal, CTCAE version 4.03
grade 3 or higher and treatment related AEs reported throughout the conduct of the study will be 
tabulated by preferred term and/or system organ class. CTCAE grade changes in safety 
laboratory values will be summarized with descriptive statistics. The incidence of concomitant 
medications will be summarized.
Tables and/or narratives of deaths and treatment related SAEs will be provided.
10.8.8.
Long-term Data Analysis
All subjects will be followed for survival for up to approximately 15 years after the last subject
receives their KTE-X19 infusion. No formal hypothesis testing will be performed based on data 
obtained after the cutoff for the primary analysis. Descriptive estimates of key efficacy and 
safety analyses may be updated to assess the overall treatment profile.
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11.
REGULATORY OBLIGATIONS 
11.1.
Independent Review Board /Independent Ethics Committee 
A copy of the protocol, ICF and any additional subject or trial information such as subject 
recruitment materials must be submitted to each sites respective IRB/IEC for approval. Once 
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 serious adverse 
events (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 contained at all material submitted to the key sponsor contact.
The following rules are to be applied.

Subjects will be identified by a unique identification number

Date of birth or year of birth/age at time of enrollment will be reported according with local 
laws and regulations
For reporting of serious adverse events, subjects will be identified by their respective subject 
identification number, initials and data of birth (as per their local reporting requirements for both 
initials and date of birth)
Per federal regulations and ICH/GCP guidelines, investigators and institutions are required to 
permit authorization to the sponsor, 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 under the following criteria:

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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12.
PROTOCOL AMENDMENTS AND TERMINATION
If the protocol is amended, the investigators 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 and the investigator reserve the right to terminate the investigators 
participation in the study as per the terms of the agreement in the study contract. The 
investigator is to provide written communication to the IRB/IEC of the trial completion or early 
termination and provide the CRO with a copy of the correspondence.
Kite Pharma reserves the unilateral right, at is sole discretion, to determine whether to 
manufacture KTE-X19 T cells and provide them to sites and subjects after the completion of the 
study and before treatment becomes commercially available.
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13.
STUDY DOCUMENTATION AND ARCHIVE
The investigator will maintain a list of qualified staff to whom study responsibilities have been 
delegated. These individuals authorized to fulfil these responsibilities should be outlined and 
included in the Delegation of Authority Form.
Source documents are original documents, data and records for which the study data are 
collected and verified. Example of such source documents may include, but are not limited to,
hospital records and patient charts, laboratory, pharmacy, radiology and records, subject diaries, 
microfiches, correspondence and death registries. Case report form entries may be considered as 
source data if the site of the original data collection is not available. However use of the CRFs as 
source documentation as a routine practice is not recommended.
The investigator and study staff are responsible for maintaining a comprehensive and centralize 
filing system of all subject records that are readily retrieved to be monitored and or audited at 
any time by the key sponsor contact, regulatory authorities and IRB/IECs. The filing system will 
include at minimum:

Subject content including ICFs and subject identification lists

Protocols and protocol amendments, investigator 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 and the investigator. Should storage no longer be available to 
archive source documents or must be moved to an alternative location, the research staff should 
notify the key sponsor contact prior to the shipping the documents.
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14.
STUDY MONITORING AND DATA COLLECTION
The key sponsor contact, monitors, auditors or regulatory inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and verifying 
source documents and records assuring that subject confidentially is respected.
The monitor is responsible for source document verification of CRF data at regular intervals 
during the study. Protocol adherence, accuracy and consistency of study conduct and data
collection with respect to local regulations will be confirmed. Monitors will have access to 
subject records as identified in Section 13.
By signing the investigator agreement, the investigator agrees to cooperate with the monitor to 
address and resolve issues identified during monitoring visits.
In accordance with ICH GCP and the audit plan, a site may be chosen for a site audit. A site 
audit would include, but is not limited to, an inspection of the facility (ies), review of subject and 
study related records, and compliance with protocol requirements as well as ICH GCP and 
applicable regulatory policies.
All data will be collected in an electronic CRF system. All entries must be completed in English 
and concomitant medications should be identified by tradenames. For further details 
surrounding the completion of CRFs, refer to the CRF completion guidelines.
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15.
PUBLICATION
Authorship of publications from data generated in study KTE-C19-103 will be determined based 
on the uniform requirements for manuscripts submitted to biomedical journals (as outlined in the 
International Committee of Medical Journal Editors December 2013) which states: 

Authorship should be based on
Substantial contributions to the conception or design of the work, acquisition of data,
analysis, or interpretation of data for the work AND
Drafting the article or revising it critically for important intellectual content; AND
Final approval of the version to be published; AND
Agreement to be accountable for all aspects of the work in ensuring that questions related 
to the accuracy or integrity of any part of the work re appropriately investigated or 
resolved
When a large, multicenter group has conducted the work, the group should identify the 
individuals who accept direct responsibility for the manuscript. This individual should fully 
meet the criteria for authorship defined above.
Funding, collection of data or general supervision of the research alone or in combination does 
not qualify an individual for authorship.
Any publication, in any form, that is derived from this study must be submitted to Kite Pharma 
for review and approval. The study contract between the institution, principal investigation and 
Kite Pharma or its delegate will outline the requirements for publication review.
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16.
COMPENSATION
Kite Pharma will provide compensation for study related illness or injury pursuant to the 
information outlined in the injury section of the ICF.
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17.
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Herzig RH, Bortin MM, Barrett AJ, Blume KG, Gluckman E, Horowitz MM, et al. Bone-
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Kantarjian H, Thomas D, O'Brien S, Cortes J, Giles F, Jeha S, et al. Long-term follow-up results 
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Kantarjian HM, O'Brien S, Smith T, Estey EH, Beran M, Preti A, Pierce S, Keating MJ. Acute 
lymphocytic leukaemia in the elderly: characteristics and outcome with the vincristine-
adriamycin-dexamethasone (VAD) regimen. British Journal of Haematology. 1994;88(1):94-
100.
Kershaw MH, Westwood JA, Darcy PK. Gene-engineered T cells for cancer therapy. Nature 
Reviews Cancer. 2013;13(8):525-41.
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New York: Springer; 2005.
Kochenderfer JN, Dudley ME, Kassim SH, Carpenter RO, Yang JC, Phan GQ, et al. Effective 
Treatment Of Chemotherapy-Refractory Diffuse Large B-Cell Lymphoma With Autologous T 
Cells Genetically-Engineered To Express An Anti-CD19 Chimeric Antigen Receptor. Blood. 
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Kochenderfer JN, Dudley ME, Kassim SH, Somerville RP, Carpenter RO, Stetler-Stevenson M, 
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 
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Kolb H-J, Simoes B, Schmid C. Stem cell transplants for patients with relapsed/refractory 
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Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, et al. T 
cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children 
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signatures of cytokine release syndrome and neurologic events in a multicenter registrational trial 
(ZUMA-1) in subjects with refractory diffuse large B cell lymphoma treated with axicabtagene 
ciloleucel (KTE-C19). Cancer Research. 2017;77(13 Supplement):CT020-CT.
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T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507-17.
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Shah B, Huynh V, Sender LS, Lee DW, Castro JE, Wierda WG, et al. High Rates of Minimal 
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18.
APPENDICES
Appendix 1.
OVERALL DISEASE RESPONSE CLASSIFICATION
Appendix 2.
EXTRAMEDULLARY DISEASE RESPONSE
Appendix 3.
SCHEDULE OF ASSESSMENTS FOR GERMAN SUBJECTS FOLLOWING 
KTE-X19 INFUSION
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Appendix 1.
OVERALL DISEASE RESPONSE CLASSIFICATION 
Response
BM
Peripheral Blood d
CNS 
EMD
Non-CNS 
EMD b, e
CR
≤ 5% f
and
ANC ≥ 1,000 and Plt ≥ 100,000
and
CNS-1
and
CR c
CRi
ANC ≥ 1000 and Plt < 100,000
OR
ANC < 1000 and Plt ≥ 100,000
CRh
ANC ≥ 500 and Plt ≥ 50,000 
but not CR
Blast-free 
hypoplastic or 
aplastic BM
Any values not meeting criteria for 
CR, CRi or CRh
PR
All criteria for CR, CRi, CRh or blast-free hypoplastic or aplastic bone 
marrow are met
and
PR
Relapse
>5% f 
or
Circulating leukemia present a
or
CNS-2 or 
CNS-3
or
PD
No response
All required assessments are performed with failure to attain the criteria needed for any response 
category
Unknown
Assessment is not done, incomplete, or indeterminate
Note: Overall disease response can be assessed as ‘Relapsed disease’ if any single element of 
disease response assessment shows relapse, other Unknown elements of disease response 
assessment do not need to be evaluated
ANC = absolute neutrophil count; BM = bone marrow; EMD = extramedullary disease; Plt = platelets; 
a 
No circulating leukemia is < 1% circulating blasts by morphology; Circulating leukemia is ≥ 1% circulating blasts by 
morphology; If ≥1% blast by morphology and there is no other evidence of leukemia, then flow or molecular studies should 
be conducted to confirm that blasts are leukemia.
b 
See Overall Non-CNS EMD table (Appendix 2)
c 
If baseline EMD is present, then images must show CR. If no baseline EMD, then images are not required, but if 
performed, must show CR per Appendix 2.
d 
ANC and Plt:  The units for Plt and ANC are per uL.  ANC and Plt values should be evaluated every time a BM evaluation 
is performed.  If not done, ANC and Plt values used for response assessment can be from any time 7 days prior to the BM 
result to any time after the BM result. 
e 
In subjects evaluated for non-CNS EMD, imaging and bone marrow results used for assessment of overall disease response 
must be within 30 days of each other
f
Blasts by morphology in BM
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Appendix 2.
EXTRAMEDULLARY DISEASE RESPONSE
Subjects with known baseline extramedullary disease (EMD) should have disease assessed by 
the investigator per the Table below at baseline and post-baseline with an imaging modality 
appropriate for the anatomical site and clinical scenario (eg, MRI for CNS lesion, ultrasound for 
testicular lesion, CT for intra-abdominal or thoracic lesion) and with the same imaging modality
throughout.  
Response a
PET
Baseline, 
On-study
Baseline lesion(s) 
(by CT or MRI) b
New Lesion(s)
CR
Neg, N/A
and
All of:

Disappearance of measurable and non-measurable 
nodal lesions: 
o
Nodal masses >1.5 cm in greatest 
transverse diameter (GTD) at baseline must 
have regressed to ≤1.5 cm in GTD
o
Nodes that were 1.1 to 1.5 cm in their long 
axis and more than 1.0 cm in their short 
axis before treatment must have decreased 
to 1.0cm in their short axis after treatment

If testes, spleen and/or liver involvement, they must 
be normal size by imaging or physical examination.
and
No
Pos, Neg
and
Any
and
No
PR
Any
and
All of:

≥ 50% decrease in sum of the product of the 
diameters (SPD) of up to 6 of the largest dominant 
masses. Dominant masses should be clearly 
measurable in at least 2 perpendicular dimensions, 
and should be from different regions of the body if 
possible. 

No increase in size of liver or spleen by imaging or 
physical exam

If multiple splenic and hepatic nodules are present, 
they must regress by ≥ 50% in the SPD. There must 
be a > 50% decrease in the greatest transverse 
diameter for a single nodule. 
and
No
SD
Does not meet the criteria for CR, PR, or PD
PD
Any
and
At least one of the following:

≥ 50% increase from nadir in the sum of the 
products of at least two lymph nodes, or if a single 
node is involved at least a 50% increase in the 
product of the diameters of this one node. 

At least a 50% increase in the longest diameter of 
any single previously identified node more than 1 
cm in its short axis

Greater than or equal to a 50% increase in size of 
splenic, hepatic or any other non-nodal lesion. 
or
Yes
Neg = Negative; Pos = Positive; N/A = Not applicable
a
Modified Revised IWG Criteria (Cheson et al, 2007)
b
see Section 7.9.2 of protocol for details.
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Appendix 3.
SCHEDULE OF ASSESSMENTS FOR GERMAN SUBJECTS 
FOLLOWING KTE-X19 INFUSION
The post-infusion monitoring of subjects, described in section 7.11.7.2 in this protocol, will 
be extended by monitoring on Day 8, Day 9, and Day 10, according to procedures outlined 
in the Schedule of Assessment Table, column “IP administration period, 1-7”. The subject 
may stay hospitalized or return to the clinic daily for this extended monitoring at the 
discretion of the investigator.
The daily monitoring will include vital signs (see section 7.4), blood draw for chemistry 
panel with CRP, ferritin (and LDH if indicated as per section 7.11.7.4), blood draw for 
CBC w/differential, and neurological assessment (see section 7.5). Any observed toxicity 
will be managed according to section 6.10 of this protocol.
KTE-C19 
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SAP_001.pdf: 
Sponsor:
Kite Pharma, Inc.
2400 Broadway
Santa Monica, CA 90404
United States of America
Product Name:
KTE-X19
Protocol:
A Phase 1/2 Multi-Center Study Evaluating the Safety and 
Efficacy of KTE-X19 in Adult Subjects with 
Relapsed/Refractory B-precursor Acute Lymphoblastic 
Leukemia (r/r ALL) (ZUMA-3)
Version Number:
Version 2.0
Release Date:
06 July 2020
Replaces Previous Version(s):
Version 1.0; dated 16 May 2018
CONFIDENTIALITY NOTICE
This document contains confidential information of Kite Pharma Inc., a wholly owned subsidiary 
of Gilead Sciences Inc. This document must not be disclosed to anyone other than the site 
research staff and members of the Institutional Review Board/Independent Ethics Committee, a 
scientific review board or an equivalent. The information in this document cannot be used for 
any purpose other than the conduct of the clinical investigation without the prior written consent 
of Kite Pharma Inc. Questions regarding how this document should be used or the conduct of the 
clinical trial should be directed to the key sponsor contacts.


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TABLE OF CONTENTS
TABLE OF CONTENTS ..............................................................................................................................................2
LIST OF IN-TEXT TABLES........................................................................................................................................3
LIST OF ABBREVIATIONS AND DEFINTIONS OF TERMS .................................................................................4
1.
INTRODUCTION ................................................................................................................................................6
2.
OBJECTIVES.......................................................................................................................................................7
3.
STUDY OVERVIEW...........................................................................................................................................8
3.1.
Study Design............................................................................................................................................8
3.2.
Hypothesis................................................................................................................................................8
3.3.
Sample Size Considerations.....................................................................................................................8
3.4.
Statistical Assumptions ............................................................................................................................9
4.
STUDY ENDPOINTS AND COVARIATES ....................................................................................................10
4.1.
Endpoints ...............................................................................................................................................10
4.2.
Covariates...............................................................................................................................................11
5.
DEFINITIONS....................................................................................................................................................13
5.1.
General...................................................................................................................................................13
5.2.
Safety .....................................................................................................................................................13
5.3.
Efficacy..................................................................................................................................................15
6.
ANALYSIS SUBSETS.......................................................................................................................................18
6.1.
mITT ......................................................................................................................................................18
6.2.
Safety Analysis Set ................................................................................................................................18
6.3.
FAS ........................................................................................................................................................18
6.4.
mITT Retreatment Analysis Set.............................................................................................................18
6.5.
Safety Retreatment Analysis Set............................................................................................................18
6.6.
Subgroup Analysis Sets..........................................................................................................................18
6.7.
DLT-evaluable Analysis Set ..................................................................................................................18
7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES...................................................................19
7.1.
Phase 1 – Safety Interim Analyses.........................................................................................................19
7.2.
Phase 2 – Interim Safety Analyses.........................................................................................................19
7.3.
Access to Aggregate and Subject-level Data and Individual Subject Treatment Assignments..............20
8.
DATA SCREENING AND ACCEPTANCE......................................................................................................21
8.1.
General Principles ..................................................................................................................................21
8.2.
Electronic Transfer and Archival of Data ..............................................................................................21
8.3.
Handling of Missing and Incomplete Data.............................................................................................21
8.3.1.
Efficacy ................................................................................................................................21
8.3.2.
Safety....................................................................................................................................21
8.4.
Detection of Bias....................................................................................................................................21
8.5.
Outliers...................................................................................................................................................22
8.6.
Distributional Characteristics.................................................................................................................22
8.7.
Validation and Configuration Management ...........................................................................................22
9.
STATISTICAL METHODS OF ANALYSIS ....................................................................................................23
9.1.
General Principles ..................................................................................................................................23
9.2.
Subject Accountability...........................................................................................................................23
9.3.
Important Protocol Deviations ...............................................................................................................23


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9.4.
Demographic and Baseline Characteristics............................................................................................23
9.5.
Efficacy Analyses...................................................................................................................................23
9.5.1.
OCR (CR + CRi) Rate..........................................................................................................24
9.5.2.
DOR .....................................................................................................................................25
9.5.3.
Rate of MRD− Remission ....................................................................................................25
9.5.4.
Allo-SCT Rate......................................................................................................................25
9.5.5.
Relapse-free Survival ...........................................................................................................25
9.5.6.
Overall Survival ...................................................................................................................26
9.5.7.
OCR (CR + CRi) Rate Among Subjects Retreated with KTE-X19 .....................................26
9.5.8.
DOR Among Subjects Retreated with KTE-X19.................................................................26
9.6.
Safety Analyses......................................................................................................................................26
9.6.1.
AEs.......................................................................................................................................27
9.6.2.
Procedures and Concomitant Medications ...........................................................................28
9.6.3.
Laboratory Test Results........................................................................................................28
9.6.4.
Anti-CD19 CAR Antibodies ................................................................................................28
9.6.5.
RCR......................................................................................................................................28
9.6.6.
Exposure to Study Treatment...............................................................................................28
9.6.7.
Exposure to Concomitant Medications and Procedures .......................................................28
9.6.8.
EQ-5D for Subjects in Phase 2.............................................................................................29
9.7.
Subsequent Anticancer Therapy.............................................................................................................29
9.8.
Schedule of Study Treatment .................................................................................................................29
9.9.
Lymphocyte Subsets ..............................................................................................................................29
10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES.............................................................................30
11.
REFERENCES ...................................................................................................................................................31
12.
HISTORY OF REVISIONS ...............................................................................................................................32
13.
APPENDICES ....................................................................................................................................................33
LIST OF IN-TEXT TABLES
Table 1.
Imputation Rules for Partial or Missing Start Dates...............................................................33


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LIST OF ABBREVIATIONS AND DEFINTIONS OF TERMS
ADaM
Analysis data model
AE
Adverse event
ALL
Acute Lymphoblastic Leukemia
allo SCT
Allogeneic stem cell transplant
BFBM
Blast-free hypoplastic or aplastic bone marrow rate
CAR
Chimeric antigen receptor 
CI
Confidence interval
CMH
Cochran-Mantel-Haenszel
CNS
Central nervous system
CR
Complete response
CRF
Case report form
CRh
CR with partial hematological recovery
CRi
CR with incomplete hematologic recovery
CRS
Cytokine release syndrome
CSF
Cerebrospinal fluid
CSR
Clinical study report
CT
Computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DLT
Dose limiting toxicity
DMP
Data management plan
DOR
Duration of response
DORR
Duration of response to retreatment
DSMB
Data Safety Monitoring Board
ECOG
Eastern Cooperative Oncology Group
EFS
Event-free survival
EQ-5D-5L
European quality of life five dimensions five levels
FAS
Full analysis set
GVHD
Graft versus host disease
HDT
High-dose therapy 
HLGT
High-level group term
IVIG
Intravenous immunoglobulin
KM
Kaplan-Meier
MedDRA
Medical Dictionary for Regulatory Activities
mITT
Modified intent-to-treat
MLL
Mixed lineage leukemia
MRD
Minimal residue disease
NE
Neurologic event
OCR
Overall complete remission
OS
Overall survival


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PFS
Progression-free survival
PR
Partial remission
PRO
Patient reported outcome
RCR
Replication-competent retrovirus
RFS
Relapse free survival
r/r
Relapsed/refractory
SAE
Serious adverse event
SCT
Stem cell transplant
SDTM
Study data tabulation model 
SOC
System organ class
SOP
Standard operating procedures
SMQ
Standardized MedDRA query
SRT
Safety review team
SUSAR
Suspected unexpected serious adverse reaction
TEAE
Treatment-emergent adverse event
TFL
Tables, figures, and listings
TID
Trial integrity document
TKI
Tyrosine kinase inhibitor
VAS
Visual analog scale
WHO
Would health organization


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1.
INTRODUCTION
This statistical analysis plan provides the prespecification and details for the statistical analyses 
outlined within protocol KTE-C19-103 entitled “A Phase 1/2 Multi-Center Study Evaluating the 
Safety and Efficacy of KTE-X19 in Adult Subjects with Relapsed/Refractory B-precursor Acute 
Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)”. The scope of this plan includes the interim, 
primary, and final analyses that are planned.


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2.
OBJECTIVES
The primary objective of Phase 1 is to evaluate the safety of KTE-X19 and determine the dosage 
for Phase 2.
The primary objective of Phase 2 is to evaluate the efficacy of KTE-X19, as measured by the 
overall complete remission (OCR) rate defined as the proportion of subjects achieved either 
complete response (CR) or CR with incomplete hematologic recovery (CRi) in this study.
Secondary objectives will include assessing the safety and tolerability of KTE-X19 and 
additional efficacy endpoints.


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3.
STUDY OVERVIEW
3.1.
Study Design
Study KTE-C19-103 is a Phase 1/2 multicenter, open-label study evaluating the safety and 
efficacy of KTE-X19 in adult subjects with r/r ALL. The trial will be separated into 2 distinct 
phases designated as Phase 1 and Phase 2.
During Phase 1, approximately 3 to 12 subjects with high-burden [M3 marrow (> 25% leukemic 
blasts) or ≥1000 blasts/mm3 in the peripheral circulation] r/r ALL disease who are evaluable for 
dose-limiting toxicity (DLT) 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 the safety data and make recommendations regarding further enrollment 
in Phase 1 or proceeding to Phase 2 based on the incidence of DLTs and overall safety profile of 
KTE-X19. Up to approximately 40 additional subjects with high- or low-burden disease may be 
enrolled to further assess safety in Phase 1. The DLT definition and assessment is described in 
the study protocol. 
During Phase 2, approximately 50 subjects with r/r ALL treated with KTE-X19 will be assessed 
to evaluate the efficacy and safety of KTE-X19. One interim and one primary analysis will be 
performed. A Data Safety Monitoring Board (DSMB) will review safety data after 20 subjects in 
Phase 2 have been treated and followed for 30 days. 
The primary analysis will occur when the overall study enrollment is complete, and the last 
subject treated with KTE-X19 has had the opportunity to complete the 6-month disease 
assessment. The final analysis will occur when all subjects have completed the study. 
3.2.
Hypothesis
This study is designed to differentiate between a treatment that has a true OCR rate of 40% or 
less and a treatment with a true OCR rate of 65% or more. The hypothesis is that the OCR rate 
with KTE-X19 treatment is significantly greater than the historical control rate of 40%, ie,
:  ≤0.4 . :  > 0.4
3.3.
Sample Size Considerations
Three to 12 subjects will be enrolled to evaluate for DLT in Phase 1, and up to approximately 
40 additional subjects will be enrolled into Phase 1 of this study.
If the study proceeds to Phase 2, approximately 50 subjects will be enrolled into Phase 2.
Approximately 100 subjects may be enrolled and treated in the entire study (both Phase 1 and 
Phase 2).
KTE-X19 doses will range from 0.5 x 106 to 2 x 106 cells/kg. For the Phase 1 portion of the 
study and the evaluation of DLT, the doses are 2.0 x 106 anti-CD19 CAR T cells/kg (± 20%),
1.0 x 106 anti-CD19 CAR T cells/kg (± 20%), or 0.5 x 106 anti-CD19 CAR T cells/kg (± 20%).
For subjects weighing greater than 100 kg, a maximum flat dose of 2 x 108, 1 x 108, or 0.5 x 108
anti-CD19 CAR T cells will be administered.


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Efficacy analyses will be based on a modified intent-to-treat (mITT) population consisting of all 
subjects enrolled in the Phase 2 portion of the study who receive KTE-X19 at any dose.
Efficacy analyses may also be based on a full analysis set (FAS) population consisting of all 
subjects enrolled in the Phase 2 portion of the study. 
Safety analyses will be based on all subjects dosed with KTE-X19.
DLT analyses will be based on the DLT-evaluable analysis set, defined in Section 6.7.
This study uses a single-arm design to test for an improvement in OCR rate. A sample size of 
50 KTE-X19 subjects in Phase 2 provides approximately 93% power to distinguish between an 
active therapy with a 65% true OCR rate from a therapy with a response rate of 40% or less, with 
the one-sided alpha level of 0.025. A step-down test of the secondary endpoint minimal residual 
disease negative (MRD ) rate will be performed against an MRD
rate of 30% if the testing of 
the OCR rate is significant. EAST version 6 was used to evaluate the operating characteristics of 
this design.
The hypothesis of MRD- will only be performed if the primary efficacy endpoint OCR rate 
reaches statistical significance, so that the family-wise type I error will be controlled at one-sided 
2.5% level under this hierarchical testing scheme. 
During Phase 2, 1 interim and 1 primary analysis will be performed. 

The interim analysis will occur after 20 subjects in the mITT analysis set have had the 
opportunity to be followed for 30 days; this analysis will be for the assessment of safety only.
The DSMB will review the 20-patient interim analysis.

The primary analysis will occur when the overall study enrollment is complete and the last 
treated subject in the mITT analysis set has had the opportunity to complete the 6-month
disease assessment after KTE-X19 infusion.
At the time of the primary analysis, if either less than or more than 50 subjects are eligible for the 
mITT analysis set, all mITT-eligible subjects will be included in the analysis. 
3.4.
Statistical Assumptions
This study assumes that the underlying overall complete remission rate (in the absence of 
treatment with investigational therapy) is 40% and that an improvement in the overall complete 
remission rate to 65% provides clinically meaningful benefit. The responses from subjects in the 
study population are assumed to be independent and follow binomial distribution; therefore, an 
exact binomial test will be used to test the statistical hypothesis.
For MRD
rate, it is assumed that the underlying response rate (in the absence of treatment with 
investigational therapy) is 30%.


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4.
STUDY ENDPOINTS AND COVARIATES
4.1.
Endpoints
Primary endpoint (Phase 1): The incidence of adverse events (AEs) defined as DLTs in the 
DLT-evaluable set
Primary endpoint (Phase 2): OCR (CR + CRi) rate per independent review
Secondary endpoints (Phase 2, unless noted): 

MRD
remission rate

CR rate per independent review

CRi rate per independent review

Duration of Remission (DOR) per independent review

OCR (CR + CRi) rate per investigator review

Allogeneic stem cell transplant (allo-SCT) rate

Rate of MRD
CR

Rate of MRD
CRi

Overall survival (OS)

Relapse-free survival (RFS)

Incidence of AEs and clinically significant changes in safety laboratory values

Incidence of anti-CD19 CAR antibodies

Changes over time in the EQ-5D scale score and EQ-5D visual analogue scale (VAS) score
Exploratory endpoint:

The OCR (CR + CRi) rate, rate of MRD negative remission, and DOR among subjects 
retreated with KTE-X19

Survival rate and non-relapse survival rate 100 days after allo-SCT

CR with partial hematological recovery (CRh) 

Blast-free hypoplastic or aplastic bone marrow rate (BFBM)


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
Rate of MRD
CRh

Rate of MRD
BFBM

Partial remission (PR) rate

Level and activity of CAR T cells, as well as presence and status of CD19+ cells in blood 
and bone marrow

Levels of cytokines in serum and cerebrospinal fluid (CSF)
Endpoints related to product characterization (level and activity of CAR T cells), presence and 
status of CD19+ cells in blood and bone marrow, as well as analyses related to these endpoints 
will be described in a supplemental statistical analysis plan.
4.2.
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 at baseline (< 65 years, ≥65 years)

Sex (male, female)

Race: white, black or African American, Asian, American Indian or Alaska Native, Native 
Hawaiian or Other Pacific Islander, other (categories may be collapsed or expanded based on 
accrual)

Region (North America, Europe)

Relapsed or refractory (r/r) Subgroup (primary refractory [refractory to first-line therapy],
first relapse if duration of first remission was < 12 months, r/r to 2nd or greater line therapy, 
r/r after allo-SCT)

Prior blinatumomab treatment (yes, no)

Prior inotuzumab treatment (yes, no)

Prior allo-SCT (yes, no)

Extramedullary disease (yes, no)

Lines of prior therapies (1, 2, > 2; categories may be modified based on accrual)

% bone marrow blasts at screening (< 50%, ≥50%)


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
Peripheral blasts (0, > 0 to 1000, > 1000 blasts/mm3)

Normal karyotype

CD19 expression based on central read (positive, negative)

Philadelphia chromosome t(9;22) (yes, no)

Mixed lineage leukemia (MLL) translocation t(4;11) t(8;14) (yes, no)

Complex karyotype (≥5 chromosomal abnormalities) (yes, no)

Low hypodiploidy (30-39 chromosomes) (yes, no)

Near triploidy (60-78 chromosomes) (yes, no)

Bridging chemotherapy (yes, no)
Covariate levels that are sparse may be collapsed for purposes of statistical modeling.


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5.
DEFINITIONS
5.1.
General
Study enrollment: Study enrollment occurs when the subject commences leukapheresis. 
Study Day 0: Study Day 0 is defined as the day the subject received the first KTE-X19 infusion.
The day prior to Study Day 0 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 value taken prior to conditioning 
chemotherapy.
Study therapy: Study therapy includes bridging chemotherapy, CSF prophylaxis, conditioning 
chemotherapy, and KTE-X19.
On-study: time from enrollment to the last date of contact or death
r/r subgroup: The r/r subgroups are defined as below:

r/r disease after allo-SCT: A subject is considered to be r/r after allo-SCT if the subject 
experienced relapse or failed to achieve CR after allo-SCT

Primary refractory: A subject is considered to be primary refractory if the subject failed to 
achieve CR to first-line therapy. 

r/r to 2nd- or greater-line therapy: A subject is considered to be r/r to 2nd- or greater-line 
therapy if the subject failed to achieve CR or relapsed after the 2nd- or greater-line therapy. 

First relapse with first remission ≤ 12 months: A subject is considered to be first relapse with 
first remission ≤ 12 months if the subject achieved CR but relapsed within 12 months. 
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 or last date known to 
be alive, 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
Treatment-emergent AE (TEAE): Any AE with an onset on or after the KTE-X19 infusion.
For subjects who are retreated with KTE-X19, TEAEs during the retreatment period may be 
summarized separately. 


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KTE-X19 Retreatment period (defined only for subjects who undergo retreatment with 
KTE-X19): The KTE-X19 retreatment period begins on the day of the first dose of conditioning 
chemotherapy for retreatment or retreatment enrollment date, whichever is earlier.
Deaths: All deaths that occur after leukapheresis will be summarized. For subjects who undergo
retreatment with KTE-X19, deaths that occur during the retreatment period may also be 
summarized separately. 
AEs of special interest: AEs of interest for KTE-X19 treatment include the following 
categories:
Identified risks:

Cytokine release syndrome (CRS)

Neurologic events, including cerebral edema

Cytopenias (thrombocytopenia, neutropenia, and anemia)

Infections

Hypogammaglobulinemia
Potential risks:

Secondary malignancy

Immunogenicity

Replication-competent retrovirus (RCR)

Tumor lysis syndrome

Graft-versus-host disease (GVHD)
Time to onset and duration of the important identified risks CRS and neurologic events will be 
summarized.
CRS will be identified via collection of the syndrome on a case report form (CRF) specifically 
designed to record CRS. Specific individual symptoms of CRS (eg, fever) collected on the AE 
log will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) and linked 
to the corresponding CRS episode. Individual symptoms of CRS will be graded per Common 
Terminology Criteria for Adverse Events (CTCAE) version 4.03, and CRS as a syndrome will be 
graded per modified Lee criteria {Lee 2014}. In the modified grading scale, neurologic AEs are 
not to be reported as part of the CRS syndrome and will be reported separately and summarized 
separately. 


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Neurologic events will be identified with a search strategy based on known neurologic toxicities 
associated with anti-CD19 immunotherapy {Topp 2015}. The search strategy focuses on central 
nervous system (CNS) toxicity, without regard to relatedness, temporal relationship, or 
concomitant conditions (eg, CRS). Additionally, the MedDRA system organ classes (SOCs) of 
Psychiatric Disorders and Nervous System Disorders will be reviewed for additional events; 
these events will then be evaluated for potential inclusion as neurologic AEs.
Immunogenicity will be identified by the development of antibodies against CAR-expressing 
cells using flow cytometry. In addition, a manual review of the AE terms indicative of 
autoimmunity will be performed, including infusion-related events and anaphylactic reactions 
among subjects who test positive for anti-CD19 CAR antibodies.
For other AEs of special interest, specific AEs may be mapped to these categories using 
dictionary-coded event terms and standardized MedDRA queries (SMQs) or other search 
strategies. Specific definitions of these events and the coded terms to which they correspond will 
be provided in the Program Safety Analysis Plan.
Duration of an AE of interest: 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 stop day of the last AE in the event class
the start day of the first AE 
in the event class + 1.
5.3.
Efficacy
OCR (CR + CRi) rate: The proportion of subjects with either CR or CR with incomplete 
hematologic recovery (CRi) per independent review or investigator review prior to the 
subsequent anticancer therapy and allo-SCT.
CR rate: The proportion of subjects who experience CR, which will be analyzed per 
independent review and investigator review separately.
DOR: DOR is defined only for subjects who experience CR or CRi per independent review or 
investigator review and is the time from the first CR or CRi to relapse or death from any cause in 
the absence of documented relapse. Subjects not meeting the criteria for relapse and who have 
not died by the analysis data cutoff date will be censored at their last evaluable disease 
assessment date or disease status follow-up assessment. DOR will be derived using disease 
assessments obtained on study prior to initiation of new anticancer therapy and allo-SCT 
(excluding resumption of tyrosine kinase inhibitor (TKI)). Disease assessments obtained after 
new anticancer therapies including allo-SCT will not contribute to the derivation of DOR. The 
DOR for subjects who undergo allo-SCT while in remission will be censored at the last 
evaluable disease assessment prior to the allo-SCT; the DOR for subjects who undergo other new 
anticancer therapies in the absence of documented relapse is censored at the last evaluable 
disease assessment prior to the new anticancer therapies. A sensitivity analysis will be conducted 
in which the DOR in subjects who received subsequent allo-SCT will not censor at the last 
disease assessment prior to SCT, and instead, the response after SCT will contribute to the 
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In subjects who resume TKI therapy, disease assessments obtained after resumption of TKI 
therapy will contribute to the derivation of DOR. A sensitivity analysis will be conducted in 
which the DOR in such subjects is censored at the last evaluable disease assessment prior to the 
resumption of TKI therapy.
A sensitivity analysis may be conducted in which receiving allo-SCT or subsequent anti-cancer 
therapy are considered events.
Further details on the derivation of DOR are provided in Appendix 2.
DOR analysis will be conducted per independent review and investigator review separately. Both 
the mITT analysis set and the full analysis set (FAS) will be used. 
MRD
remission rate: The incidence of an MRD
response. MRD
is defined as MRD < 10 4
per the standard assessment as described in the protocol. MRD
remission rate will be estimated 
for all dosed subjects, subjects with a CR, subjects with a CRi, and subjects with either a CR or a 
CRi combined. MRD
remission rate will also be estimated for subjects with CRh and blast-free 
hypoplastic or aplastic bone marrow.  
Allo-SCT rate: the incidence of allo-SCT among subjects who have been treated with 
KTE-X19.
OS: OS for the mITT analysis set is defined as the time from the KTE-X19 infusion to the date 
of death from any cause.
OS for all enrolled subjects in the FAS is defined as the time from enrollment to the date of death 
from any case. 
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. 
Further details on the derivation of OS and the specific data modules that will be used to derive 
the last date known to be alive are provided in Appendix 2.
Relapse-free Survival (RFS): RFS for the mITT analysis set is defined as the time from the 
KTE-X19 infusion date to the date of disease relapse or death from any cause. RFS for all 
enrolled subjects in the FAS is defined as the time from enrollment to the date of disease relapse 
or death from any cause. Subjects who have not achieved a CR or CRi at the analysis data cutoff 
will be evaluated as having an RFS event at Day 0 for RFS analysis on mITT set, or at the date 
of enrollment for RFS analysis on FAS set. Subjects not meeting the criteria for relapse by the 
analysis data cutoff date will be censored at their last evaluable disease assessment date or 
disease status follow up assessment. RFS will be derived using disease assessments obtained on 
study prior to initiation of new anticancer therapy and allo-SCT (excluding resumption of a 
TKI). A sensitivity analysis will be conducted in which the RFS in subjects who received 
subsequent allo-SCT will not be censored at the last disease assessment prior to SCT, and 
instead, the response after SCT will contribute to the derivation of RFS.


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In subjects who resume TKI therapy, disease assessments obtained after resumption of TKI 
therapy will contribute to the derivation of RFS. A sensitivity analysis will be conducted in 
which the RFS in such subjects is censored at the last evaluable disease assessment prior to the 
resumption of TKI therapy. Further details on the derivation of RFS are provided in Appendix 2.
OCR (CR + CRi) rate for retreatment: the incidence of OCR rate for subjects in the 
retreatment period.
DOR to retreatment (DORR): DORR is defined only for subjects who experience OCR to 
retreatment and is the time from the first OCR after retreatment to relapse after retreatment or 
death from any cause in the absence of documented relapse.
MRD
remission rate for subjects with CRh: The incidence of an MRD  response for 
subjects who had the best response of CRh. MRD
is defined as MRD < 10 4.
MRD
remission rate for subjects with blast-free hypoplastic or aplastic bone marrow: The 
incidence of an MRD  response for subjects who had the best response of blast-free hypoplastic 
or aplastic response. MRD
is defined as MRD < 10 4.
Mortality rate 100 days after allo-SCT: The rate of deaths within 100 days after allo-SCT for 
subjects who undergo allo-SCT.
PR rate: The incidence of PR. 
Changes over time in the EQ-5D scale score and EQ-5D VAS score: The changes of the 
EQ-5D scale score and EQ-5D VAS score at each assessment time compared to baseline will be 
presented.


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6.
ANALYSIS SUBSETS
The following analysis sets are defined for each study phase separately.
6.1.
mITT
The mITT analysis set will consist of all subjects enrolled and treated with KTE-X19 in Phase 2.
This analysis set will be used for all efficacy analyses unless specified otherwise.
6.2.
Safety Analysis Set
The safety analysis set is defined as all subjects treated with any dose of KTE-X19.
6.3.
FAS
The FAS will consist of all enrolled (leukapheresed) subjects and will be used for the summary 
of subject disposition, subject listings of deaths, and efficacy analyses, which is specified in 
Section 9.5.
6.4.
mITT Retreatment Analysis Set
The mITT retreatment analysis set will consist of all subjects who undergo retreatment with 
KTE-X19 at any dose administered in Phase 2. This set will be used for all retreatment efficacy 
analyses.
6.5.
Safety Retreatment Analysis Set
The safety retreatment analysis set will consist of all subjects who undergo retreatment with 
KTE-X19. This set will be used for all retreatment safety analyses.
6.6.
Subgroup Analysis Sets
Subgroup analyses of selected efficacy and safety endpoints may be performed for the baseline 
covariates defined in Section 4.2.
6.7.
DLT-evaluable Analysis Set
The DLT-evaluable analysis set includes the first 3-6 subjects in Phase 1 who are 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 postinfusion period, up to the time 
at which a dose level has been evaluated for DLT and deemed safe. Additional subjects who are 
subsequently enrolled and treated in Phase 1 for the purpose 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 
analysis set, and DLT will not be assessed for such subjects.


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7.
INTERIM ANALYSIS AND EARLY STOPPING GUIDELINES
The SRT will review the safety data during Phase 1 of the study and make a recommendation to 
progress the study from Phase 1 to Phase 2 based on the incidence of DLT and review of SAEs.
The DSMB will meet once during the Phase 2 portion of the study. The DSMB will review 
safety data and will be chartered to make trial conduct recommendations based on the risk versus
benefit of treatment with KTE-X19. No early stopping for efficacy or futility is planned in the 
interim analysis.
7.1.
Phase 1 – Safety Interim Analyses
The SRT will evaluate the incidence of DLTs and SAEs after 3 subjects have been treated in a 
dose cohort and have met the criteria for the DLT-evaluable analysis set. The SRT may 
recommend progression to the Phase 2 portion of the trial.
Study enrollment may be paused in Phase 1 (DLT Evaluation Period) following any Grade 5 AE
that occurs within 30 days of KTE-X19 dosing, regardless of attributions.
7.2.
Phase 2 – Interim Safety Analyses
An independent DSMB will be chartered to make recommendations on study conduct. The 
DSMB will meet once during the study. Details may be found in the Data Safety Monitoring 
Board Charter.
The interim analysis will be conducted after 20 subjects in the mITT analysis set in Phase 2 have 
had the opportunity to be followed for 30 days after the KTE-X19 infusion. This interim analysis 
will be for safety only. 
As part of its oversight of the study, the DSMB also will assess whether to pause enrollment in 
Phase 2 after 10, 20, and 35 subjects enrolled in Phase 2 have been treated with KTE-X19 and 
have had the opportunity to be followed for 30 days. Enrollment will be paused if any of the 
following is met:

Subject incidence of the following Grade 4 KTE-X19-related AEs lasting more than 7 days is 
> 33%:
Neurotoxicity
CRS (per Lee 2014 criteria)
Other nonhematological SAE
Treatment-related infection


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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. Data handling procedures, designed to maintain 
the trial credibility and validity in this open-label single-arm study, are described in the Trial 
Integrity Document (TID).


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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 (DMP) and 
additional manual data reviews defined by the study team. Data inconsistencies will be reviewed 
and resolved before the database snapshot for the primary analysis and the final database lock.
For interim analyses, snapshots may include data that has not passed all data cleaning procedures 
at the time the data are extracted for snapshot.
8.2.
Electronic Transfer and Archival of Data
The Medidata Rave system will be used to collect the data in this study. 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, the product manufacture (total T cells, CAR T cells 
(transduction ratio), duration of manufacturing time), central laboratory assessment of subject 
serum samples (CAR T cell levels in the peripheral blood, cytokine levels, antibody assays, RCR 
testing), MRD, and central radiology and clinical review will be generated from contract 
laboratories, Kite Pharma, and central imaging vendor. These data will be transferred to Kite
study team 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 AE start dates, the 
algorithm defined in Appendix 1 will be used. Completely missing death dates or death dates 
with only a year reported will not be imputed.
8.4.
Detection of Bias
A listing of subjects with important protocol deviations will be generated. The deviations 
included in this list will include violations of eligibility criteria and violations that may have an 
impact on the efficacy evaluation. 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.


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Endpoints derived from investigator assessment of radiologic scans and clinical disease 
assessments may be subject to bias; the concordance between investigator and central review of 
radiologic scans and clinical disease assessments will be summarized.
8.5.
Outliers
Descriptive statistics will be used to identify potential outliers in any key variables analyzed.
Suspected outliers will be included in all analyses unless there is sufficient scientific justification 
to exclude them.
8.6.
Distributional Characteristics
The primary analysis of the primary endpoint is an exact binomial test used to compare the 
observed OCR rate (CR + CRi) in the mITT analysis set to an OCR rate of 40%. This test 
assumes the independence of the individual subject responses.
An exact 95% confidence interval (CI) will be generated about the response rate. 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 (TFL) will be developed and maintained according to Kite Standard 
Operating Procedures (SOP). The software and version used to generate analyses will be 
indicated in the archived documentation.


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9.
STATISTICAL METHODS OF ANALYSIS
9.1.
General Principles
The goal of the primary statistical analysis is to compare the observed OCR (CR + CRi) rate in 
the mITT analysis set to a historical control rate of 40% using an exact binomial test. Hypothesis 
testing will be 1 sided, and all 95% CIs will be 2 sided. At the time of the test of the overall study 
population, 95% CIs for the OCR rate in Phase 2 will be presented.
The timing of the interim and primary analyses will be based on subject accrual and disease 
assessment milestones. The primary analysis clinical study report (CSR) will be written at the 
primary analysis.
Analyses of the Phase 1 and Phase 2 portions of the study will be presented separately.
9.2.
Subject Accountability
The number of subjects screened, enrolled/leukapheresed, treated with bridging chemotherapy, 
treated with intrathecal chemotherapy for CSF prophylaxis, treated with conditioning 
chemotherapy, treated with KTE-X19, and retreated with KTE-X19 will be summarized. The 
reasons for discontinuing treatment and survival follow-up periods will be summarized.
Summaries of actual and potential follow-up time will be provided.
The number of subjects enrolled by country and site will be summarized.
The number of subjects in each analysis set along with reasons for exclusion will be provided.
9.3.
Important Protocol Deviations
The clinical study team will define important protocol deviation (IPD) categories and review, at 
a minimum, all IPDs prior to the database snapshot for the primary efficacy analysis. IPDs will 
be categorized by deviation type (eg, entry/eligibility, use of excluded medication). The subject 
incidence of IPDs 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
Efficacy analyses will be conducted on the mITT analysis set.
The key efficacy analyses will also be presented in the following populations:

Phase 2 FAS

Phase 1 by cohort in the safety analysis set


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
Combined Phase 1 and Phase 2 at 1.0 x 106 anti-CD19 CAR T cells/kg dose levels, both on
Subjects who have been treated with KTE-X19
FAS. 
For subjects retreated with KTE-X19, disease assessments obtained prior to retreatment but not 
disease assessment obtained after retreatment will be included in the primary summaries of OCR
rate, rate of MRD
remission, DOR, and RFS. Disease assessments obtained after retreatment 
may be included in the summaries of OCR rate, rate of MRD
remission, DOR, and RFS after 
retreatment with KTE-X19. The subject’s OS time will be derived from the last date known to be 
alive regardless of retreatment time.
9.5.1.
OCR (CR + CRi) Rate
9.5.1.1.
Primary Analysis of OCR (CR + CRi) Rate
The subject incidence of OCR (CR + CRi) will be calculated. An exact binomial test will be used 
to compare the observed OCR rate per independent review in the mITT analysis set to the 
hypothesized historical control rate of 40%. The subject incidence of best response of CR and
CRi will be tabulated. CIs will be provided about the OCR (CR + CRi) rate, as well as the CR 
rate and CRi rate separately, calculated with the Clopper-Pearson method.
The primary analysis of OCR rate will include subjects from the mITT analysis set in Phase 2. A 
sensitivity analysis of the OCR rate will be conducted in the FAS.
The CR rate will be calculated for the mITT analysis set and FAS. A 95% CI will be provided 
about the CR rate using the Clopper-Pearson method. 
9.5.1.2.
Subgroup Analyses of OCR (CR + CRi) Rate
The OCR (CR + CRi) rate with 95% CIs will be generated for subgroups of the mITT analysis 
set defined by the selected covariates as listed in Section 4.2.
A forest plot of the proportion (and 95% CI) of subjects achieving CR or CRi for each of these 
subgroups will be generated.
9.5.1.3.
Analyses of OCR Rate
Phase 1
Analyses of OCR rate in Phase 1 based on investigator assessment may occur at any time during 
Phase 1. The purpose of these analyses may include publications, preliminary evaluation of 
benefit-risk, and to inform decisions on dose.
At a minimum, CR + CRi rates, CR rates and 95% CIs will be generated for each dose cohort (if 
applicable) in Phase 1.


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9.5.2.
DOR
The primary analysis of DOR will use the Kaplan-Meier method and consider all relapses and 
deaths as events for DOR. The reverse Kaplan-Meier approach {Schemper 1996} will be used to 
estimate the follow-up time for DOR. Kaplan-Meier plots, and estimate of the median DOR, and 
2-sided 95% CIs will be generated. Estimates of the proportion of subjects who remained in 
response at 3-month intervals will be provided. The number of subjects censored and the reasons 
for censoring will be summarized. DOR will be analyzed in both mITT and FAS.
A sensitivity analysis will be conducted in which disease assessments obtained after allo-SCT 
are included in the derivation of DOR.
A sensitivity analysis of DOR will be conducted in which the DOR for subjects undergoing TKI
is censored at the last disease assessment prior to the resumption of TKI therapy.
A sensitivity analysis of DOR will be conducted in which receiving allo-SCT or subsequent 
anti-cancer therapy are considered events.
A sensitivity analysis of DOR may be conducted with non-disease mortality considered a 
competing risk. 
In the cases where subjects missed at least two consecutive visits and deemed relapse in the next 
following up visit, a sensitivity analysis of DOR may be conducted in which such cases will be 
censored at the last disease assessment before the consecutively missed disease assessment visits. 
9.5.3.
Rate of MRD
Remission
The MRD
remission rate and 95% CIs will be estimated for all treated subjects, subjects with a 
CR, subjects with a CRi, and subjects with either a CR or CRi combined.
9.5.4.
Allo-SCT Rate
The subject incidence rate of on-study allo-SCT will be summarized overall, by subjects 
achieving a CR + CRi, by subjects achieving a CR, and by subjects achieving a CRi. 
Corresponding 95% CIs may be generated.
9.5.5.
Relapse-free Survival 
Kaplan-Meier (KM) plots, estimate of the median RFS, and 2-sided 95% CIs will be generated.
Estimates of the RFS rates at 3-month intervals will be provided. The number of subjects 
censored and the reasons for censoring will be summarized. Median RFS may be estimated for 
MRD
responders and MRD+ responders.
A sensitivity analysis of RFS will be conducted in the FAS. RFS for enrolled subjects is defined 
as the time from enrollment until relapse or death from any cause. 
A sensitivity analysis will be conducted in which disease assessments obtained after allo-SCT 
are included in the derivation of RFS.


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A sensitivity analysis of RFS will be conducted in which the RFS for subjects undergoing TKI is 
censored at the last disease assessment prior to the resumption of TKI therapy.
In the cases where subjects missed at least two consecutive visits and deemed relapse in the next 
following up visit, a sensitivity analysis of RFS may be conducted in which such cases will be 
censored at the last disease assessment before the consecutively missed disease assessment visits. 
9.5.6.
Overall Survival
KM plots, estimate of the median OS, and 2-sided 95% CIs will be generated. Estimates of OS 
rates at 3-month intervals will be provided. The number of subjects censored and the reasons for 
censoring will be summarized. Median OS may be estimated for MRD
responders and MRD+
responders.
Graphical summaries of the time to CR or CRi, DOR, retreatment, relapse, and death times from 
the time of KTE-X19 infusion depicted on a horizontal time axis for each subject (“swim lane 
plot”) may be provided.
The OS will also be analyzed in the FAS. OS for enrolled subjects is defined as the time from 
enrollment until death from any cause. 
9.5.7.
OCR (CR + CRi) Rate Among Subjects Retreated with KTE-X19
The subject incidence of subjects retreated with KTE-X19 will be tabulated. The subject 
incidence of CR, CRi, and CR and CRi combined after retreatment among subjects retreated with 
KTE-X19 will be tabulated. Corresponding CIs will be provided.
9.5.8.
DOR Among Subjects Retreated with KTE-X19
The analysis of DOR to retreatment among subjects responding to retreatment with KTE-X19 
will use the same methods as the analysis of DOR.
9.6.
Safety Analyses
Safety analyses will be conducted on the safety analysis set. The primary analysis of safety data 
will summarize all AEs and laboratory values with an onset on or after the KTE-X19 infusion 
date and prior to the retreatment period (if applicable). Additional summary tables may be 
provided to present the AEs that occurred within certain study periods. For subjects who undergo 
retreatment with KTE-X19, AEs occurring in the KTE-X19 retreatment period may be 
summarized separately.
AEs will be coded with the Medical Dictionary for Regulatory Activities (MedDRA) at the time 
of each analysis. The version of the MedDRA may vary over time as the current version in use is 
updated. The severity of AEs will be graded using the CTCAE version 4.03.


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CRS will be graded using a revised CRS grading scale (see details in protocol) developed by Lee 
and colleagues {Lee 2014}. Individual symptoms associated with CRS will be graded per 
CTCAE version 4.03.
Fatal AEs that are attributed to disease progression may be included in the death summary with a 
primary death reason of “disease progression” regardless of the coded CTCAE version 4.03 
preferred term.
Subjects enrolled but not dosed with KTE-X19 will be followed for AEs for 30 days after the last 
study-specific procedure. AEs reported in these subjects will be archived in the study database 
and available in SDTM and ADAM datasets but will not be tabulated in AE summaries.
9.6.1.
AEs
The subject incidence of the following TEAEs will be tabulated:

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

Fatal AEs

AEs of interest, including identified risks and potential risks
By-subject listings of deaths through 30 days after KTE-X19 infusion and SAEs will be provided
overall and by treatment period.
Subgroup analyses of AEs may be generated for selected covariates from the list in Section 4.2.
The time to onset and resolution and the duration of CRS will be summarized. Cardiac 
arrhythmias and cardiac failure in the context of CRS may be summarized. 
The time to onset and resolution and the duration of neurologic events will be summarized. 
Cytopenias will be summarized by categories of neutropenia, anemia, and thrombocytopenia; 
cytopenias present 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).


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Potential secondary malignancies will be identified within the system organ class of neoplasms 
benign, malignant, and unspecified (including cysts and polyps). Potential secondary 
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 CTCAE version 4.03. The incidence of post-
infusion worst-grade laboratory toxicities for all analytes will be provided. Additional summaries 
for the shift from baseline to the worst toxicity grade after KTE-X19 infusion may also be 
generated.
9.6.4.
Anti-CD19 CAR Antibodies
The subject incidence of any anti-KTE-X19 antibodies will be tabulated. For subjects testing 
positive for antibodies, the persistence of the antibodies over time will be summarized.
9.6.5.
RCR
The subject incidence of RCR detected in blood samples will be tabulated overall and by 
assessment time. The persistence of RCR over time will be summarized.
9.6.6.
Exposure to Study Treatment
Summary statistics and subject listings will be provided for the following:

Total body surface area-adjusted dose of cyclophosphamide

Total body surface area-adjusted dose of fludarabine

Weight-adjusted dose of KTE-X19

Total CAR T cells of the KTE-X19 infusion

Total T cells of the KTE-X19 infusion
Separate summaries will be presented for retreatment with conditioning chemotherapy and
KTE-X19 among subjects in the safety retreatment analysis set.
9.6.7.
Exposure to Concomitant Medications and Procedures
The subject incidence of concomitant medications will be provided and summarized by 
medication category and WHO drug coded term. The subject incidence of procedures will be 
tabulated. The duration and indication of concomitant medications of interest (eg, steroids and 
tocilizumab) may be summarized. 


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9.6.8.
EQ-5D for Subjects in Phase 2
EQ-5D and VAS scores will be summarized at baseline and after study treatment visits. Changes 
in the EQ-5D and VAS scores from baseline at each post-study treatment visit will also be 
summarized with descriptive statistics.
Further analyses of these quality-of-life data may be described in a supplemental statistical 
analysis plan.
9.7.
Subsequent Anticancer Therapy
The incidence and type (by WHO drug coded term) of subsequent anticancer therapy will be 
summarized.
9.8.
Schedule of Study Treatment
Summary statistics will be provided for the following durations:

Days from leukapheresis to product release

Days from leukapheresis to receipt of KTE-X19 at the study site

Days from leukapheresis to administration of KTE-X19

Duration of hospitalization following the KTE-X19 infusion
9.9.
Lymphocyte Subsets
Summary statistics for the levels of lymphocytes and the subject incidence of lymphopenia, 
B-cell aplasia, recovery after lymphopenia, and recovery after B-cell aplasia will be provided for 
each subject based on lymphocyte subsets measured prior to conditioning chemotherapy, on the 
day of the KTE-X19 infusion, and at Week 4, Month 3, Month 6, Month 12, Month 15, and 
Month 24. Graphical summaries of the median value and interquartile range over time may be 
provided. Among subjects who experience lymphopenia or B-cell aplasia, summary statistics for 
the time to the onset of these conditions will be provided. The duration of lymphopenia and 
B-cell aplasia will be summarized; the duration of these events for subjects with persistent 
lymphopenia or B-cell aplasia at the last lymphocyte measurement will be censored at that time.
The use of IVIG treatment in the presence of B-cell aplasia may be summarized.


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10.
CHANGES FROM PROTOCOL-SPECIFIED ANALYSES
None.


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11.
REFERENCES
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, Gokbuget 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 Oncol 
2015;16 (1):57-66.


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12.
HISTORY OF REVISIONS
Version
Date
Protocol
Description of Changes
Original 
(1.0)
16 May 2018
Original to 
Amendment 5
N/A
2.0
30 May 2020
Amendment 6

Remove reference and definitions of study 
administrative periods that are irrelevant to the analysis 
from the SAP in Section 3.1;

Patients with prior Blinatumomab will be more than 
5 patients, so the primary endpoints and selected 
secondary endpoints will be evaluated in subgroup 
analysis by subjects with or without prior 
Blinatumomab;

Definition of ‘on-study’ is updated to include death 
event;

Definition of ‘actual follow-up time’ is updated to 
include last date known alive; 

Added “Time to onset, and duration of important 
identified risks CRS and neurologic events will be 
summarized.”

Methods of confidence interval calculation – only keep 
the main method: clopper-pearson and remove the 
sensitivity methods;

Added the definition of secondary malignancy.

Added the analysis of “Days from leukapheresis to 
receipt of KTE-X19 at the study site”

Minor format changes.

Re-treatment period definition updated in Section 5.2

RFS and OS for all enrolled subjects are added. 

A sensitivity analysis of DOR in which allo-SCT and 
subsequent anti-cancer therapy are considered as events 
is added. 


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13.
APPENDICES
Appendix 1.
Conventions for Clinical Data That Require Imputation for Partial or 
Missing Dates
The following data will be imputed using the following algorithm:

AE start dates

Deaths (please see exceptions below)

Concomitant medication start dates

Subsequent anticancer therapy start dates
Table 1.
Imputation Rules for Partial or Missing Start Dates
Start Date
Stop Date
Complete: yyyymmdd
Partial: yyyymm
Partial: yyyy
Missing
< Day 0
≥ Day 0
< Day 0
yyyymm
≥ Day 0
yyyymm
< Day 0
yyyy
≥ Day 0
yyyy
Partial
yyyymm
= Day 0
yyyymm
2
1
2
1
n/a
1
1
≠ Day 0
yyyymm
2
2
2
2
2
Partial
yyyy
= Day 0
yyyy
3
1
3
1
n/a
1
1
≠ Day 0
yyyy
3
3
3
3
3
Missing
4
1
4
1
4
1
1
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
Note: if the start date imputation leads to a start date that is after the stop date, then do not impute the start date.
I 
I 
I 
I 
I 
I 
I 
I 


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Imputation rules for partial or missing death dates:
1) 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.
2) 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.
Derivation of Time-to-event Endpoints and Last Date Known to Be 
Alive
Additional details on the derivations of duration of remission (DOR), relapse-free survival
(RFS), and overall survival (OS) are provided below.
1) DOR: DOR is defined only for subjects who experience a CR or CRi and is the time from the 
first OCR (CR or CRi) to relapse or death due to any cause.

Primary analysis of DOR:
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(including allo-SCT)
Event
Relapse date
Death without documented relapse and without new 
anti-cancer therapy (including allo-SCT but 
excluding resumption of TKI)
Event
Death date
Remain in remission without new anti-cancer 
therapy (including allo-SCT but excluding 
resumption of TKI) 
Censored
Last evaluable disease 
assessment date
Initiated new anti-cancer therapy (including allo-
SCT but excluding resumption of TKI) prior to 
documented relapse or death
Censored
Last evaluable disease 
assessment date prior to 
initiation of new therapy
including allo-SCT
Remain in remission without documented relapse 
and without new anti-cancer therapy (including allo-
SCT but excluding resumption of TKI) until 
withdrawal of consent or loss to follow-up
Censored
Last evaluable disease 
assessment date prior to data 
cutoff

Sensitivity analysis of DOR (not censoring at SCT):
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(excluding allo-SCT)
Event
Relapse date
Death without documented relapse and without new 
anti-cancer therapy (excluding allo-SCT and
resumption of TKI)
Event
Death date
Remain in remission without new anti-cancer 
therapy (excluding allo-SCT and resumption of TKI) 
Censored
Last evaluable disease 
assessment date
Initiated new anti-cancer therapy (excluding allo-
SCT and resumption of TKI) prior to documented 
relapse or death
Censored
Last evaluable disease 
assessment date prior to 
initiation of new therapy
excluding allo-SCT
Withdrawal of consent or lost to follow-up prior to 
documented relapse or death
Censored
Last evaluable disease 
assessment date prior to data 
cutoff


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
Sensitivity analysis of DOR (censoring for TKI):
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(including allo-SCT and resumption of TKI)
Event
Relapse date
Death without documented relapse and without new 
anti-cancer therapy (including allo-SCT and 
resumption of TKI)
Event
Death date
Remain in remission without new anti-cancer 
therapy (including allo-SCT and resumption of TKI) 
Censored
Last evaluable disease 
assessment date
Initiated new anti-cancer therapy (including allo-
SCT and resumption of TKI) prior to documented 
relapse or death
Censored
Last evaluable disease 
assessment date prior to 
initiation of new therapy
including allo-SCT and 
resumption of TKI
Withdrawal of consent or lost to follow-up prior to 
documented relapse or death
Censored
Last evaluable disease 
assessment date prior to data 
cutoff

Sensitivity analysis of DOR (both allo-SCT and subsequent therapy as events):
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(including allo-SCT)
Event
Relapse date
Death without documented relapse and without new 
anti-cancer therapy (including allo-SCT but 
excluding resumption of TKI)
Event
Death date
Remain in remission without new anti-cancer 
therapy (including allo-SCT but excluding 
resumption of TKI) 
Censored
Last evaluable disease 
assessment date
Initiated new anti-cancer therapy (including allo-
SCT but excluding resumption of TKI) prior to 
documented relapse or death
Event
Start date of new therapy 
including allo-SCT
Remain in remission without documented relapse 
and without new anti-cancer therapy (including allo-
SCT but excluding resumption of TKI) until 
withdrawal of consent or loss to follow-up
Censored
Last evaluable disease 
assessment date prior to data 
cutoff


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2) RFS: RFS for all dosed subjects on the mITT set is defined as the time from the KTE-X19 
infusion date to the date of disease relapse or death from any cause.

Primary analysis of RFS:
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(including allo-SCT)
Event
Relapse date
Subject has CR or CRi, then died without 
documented relapse and without new anti-cancer 
therapy (including allo-SCT but excluding 
resumption of TKI)
Event
Death date
Subject has disease assessment done but does not 
have a CR or CRi, or subject died or received new 
anti-cancer therapy (including allogenic SCT but 
excluding resumption of TKI) before any disease 
assessment
Event
KTE-X19 infusion date
Remain in remission and alive without new anti-
cancer therapy (including allo-SCT but excluding 
resumption of TKI) 
Censored
Last evaluable disease assessment 
date
Subject has a CR or CRi and subsequently initiated 
new anti-cancer therapy (including allo-SCT but 
excluding resumption of TKI) prior to documented 
relapse or death
Censored
Last evaluable disease assessment 
date prior to initiation of new therapy
including allo-SCT.
Remained in remission without new anti-cancer 
therapy (including allo-SCT but excluding 
resumption of TKI) until withdrawal of consent or 
loss to follow-up 
Censored
Last evaluable disease assessment 
date.
Subject enrolled and treated with KTE-X19 but the 
disease assessment has not been done and the subject 
is still alive and has not received any new anti-
cancer therapy
Censored
KTE-X19 infusion date

Sensitivity analysis of RFS (not censoring at SCT):
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(excluding allo-SCT)
Event
Relapse date
Subject has CR or CRi, then died without 
documented relapse and without new anti-cancer 
therapy (excluding allo-SCT and resumption of TKI)
Event
Death date
Subject has disease assessment done but does not 
have a CR or CRi, or subject died or received new 
anti-cancer therapy (excluding allogenic SCT and
resumption of TKI) before any disease assessment
Event
KTE-X19 infusion date


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Circumstance
Event/Censored
Date of Event/Censoring
Remain in remission and alive without new anti-
cancer therapy (excluding allo-SCT and resumption 
of TKI) 
Censored
Last evaluable disease assessment 
date
Subject has a CR or CRi and subsequently initiated 
new anti-cancer therapy (excluding allo-SCT and
resumption of TKI) prior to documented relapse or 
death
Censored
Last evaluable disease assessment 
date prior to initiation of new therapy
excluding allo-SCT.
Remained in remission without new anti-cancer 
therapy (excluding allo-SCT and resumption of TKI) 
until withdrawal of consent or loss to follow-up 
Censored
Last evaluable disease assessment 
date.
Subject enrolled and treated with KTE-X19 but the 
disease assessment has not been done and the subject 
is still alive and has not received any new anti-
cancer therapy
Censored
KTE-X19 infusion date

Sensitivity analysis of RFS (censoring at TKI):
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(including allo-SCT and resumption of TKI)
Event
Relapse date
Subject has CR or CRi, then died without 
documented relapse and without new anti-cancer 
therapy (including allo-SCT and resumption of TKI)
Event
Death date
Subject has disease assessment done but does not 
have a CR or CRi, or subject died or received new 
anti-cancer therapy (including allo-SCT and 
resumption of TKI) before any disease assessment
Event
KTE-X19 infusion date
Remain in remission and alive without new anti-
cancer therapy (including allo-SCT and resumption 
of TKI) 
Censored
Last evaluable disease assessment 
date
Subject has a CR or CRi and subsequently initiated 
new anti-cancer therapy (including allo-SCT and 
resumption of TKI) prior to documented relapse or 
death
Censored
Last evaluable disease assessment 
date prior to initiation of new therapy
(including allo-SCT and resumption 
of TKI)
Remained in remission without new anti-cancer 
therapy (including allo-SCT and resumption of TKI) 
until withdrawal of consent or loss to follow-up 
Censored
Last evaluable disease assessment 
date.
Subject enrolled and treated with KTE-X19 but the 
disease assessment has not been done and the subject 
is still alive and has not received any new anti-
cancer therapy
Censored
KTE-X19 infusion date


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3) RFS for all enrolled subjects is defined as the time from the enrollment date to the date of 
disease relapse or death from any cause.

Analysis of RFS for all enrolled subjects:
Circumstance
Event/Censored
Date of Event/Censoring
Relapse prior to initiation of new anti-cancer therapy 
(including allo-SCT)
Event
Relapse date
Subject has CR or CRi, then died without 
documented relapse and without new anti-cancer 
therapy (including allo-SCT but excluding 
resumption of TKI)
Event
Death date
Subject has disease assessment done but does not 
have a CR or CRi, or subject died or received new 
anti-cancer therapy (including allogenic SCT but 
excluding resumption of TKI) before any disease 
assessment
Event
Enrollment date
Remain in remission and alive without new anti-
cancer therapy (including allo-SCT but excluding 
resumption of TKI) 
Censored
Last evaluable disease assessment 
date
Subject has a CR or CRi and subsequently initiated 
new anti-cancer therapy (including allo-SCT but 
excluding resumption of TKI) prior to documented 
relapse or death
Censored
Last evaluable disease assessment 
date prior to initiation of new therapy
including allo-SCT.
Remained in remission without new anti-cancer 
therapy (including allo-SCT but excluding 
resumption of TKI) until withdrawal of consent or 
loss to follow-up 
Censored
Last evaluable disease assessment 
date.
Subject enrolled but the disease assessment has not 
been done and the subject is still alive and has not 
received any new anti-cancer therapy
Censored
Enrollment date
4) OS: OS is defined as the time from the KTE-X19 infusion to the date of death from any 
cause.
Circumstance
Event/Censored
Date of Event/Censoring
Death before data cutoff date for analysis
Event
Date of death
Death after data cutoff date for analysis
Censored
Data cutoff date
Known to be alive after data cutoff date for 
analysis
Censored
Data cutoff date
Alive up through data cutoff date and no 
further information available after data 
cutoff date
Censored
Last date known to be alive 
Full withdrawal of consent or lost to follow-
up prior to data cutoff date
Censored
Last date known to be alive prior to 
full consent withdrawal or lost to 
follow-up


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5) OS for all enrolled subjects, which is defined as the time from the enrollment date to the date 
of death from any cause, will use the same censoring strategy as described above.
6) 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 (including targeted AE)

Leukapheresis dates

Conditioning chemotherapy administration dates

KTE-X19 infusion dates

Bone marrow assessment dates

Cerebrospinal fluid analysis dates

Hematology specimen collection dates

Minimal residual disease analysis dates

Extramedullary disease assessment dates (including positron emissions tomography
assessment, target lesion assessment, non-target lesion assessment, new lesion assessment, 
and disease response assessment dates) 

Long-term follow-up subject status date where status  ‘alive’

End-of-treatment disposition where status is not equal to death or lost to follow-up

End of post-treatment assessment period where status is not equal to death or lost to 
follow-up

End-of-study data where end-of-study reason is not equal to death or lost to follow up