Conditions: Lymphoma, Non-Hodgkin
Keywords: Non-Hodgkin lymphoma Aggressive B-cell non-Hodgkin lymphoma Diffuse large B-cell lymphoma Relapse / refractory lymphoma Transplant not eligible High-grade B-cell lymphoma Primary central nervous system lymphoma Transformed follicular lymphoma Follicular lymphoma Grade 3B JCAR017 Liso-Cel
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 113
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of JCAR017 in participants with aggressive B-cell non-Hodgkin lymphoma (B-NHL)

Detailed description:
This is a study to determine the efficacy and safety of JCAR017 in adult participants with aggressive B-cell NHL. The study will enroll participants in Europe and Japan with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS; de novo or transformed follicular lymphoma \[tFL\]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBL), follicular lymphoma Grade 3B (FL3B), and primary central nervous system lymphoma (PCNSL). Participants with secondary central nervous system (CNS) involvement are allowed.

Once enrolled, participants will undergo leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, participants will receive lymphodepleting chemotherapy followed by infusion of JCAR017. JCAR017 will be administered by intravenous infusion. Participants will be followed for approximately 2 years after their JCAR017 infusion for safety, disease status, survival and health-related quality of life.

Delayed adverse events following exposure to gene modified T cells will be assessed and long-term persistence of these modified T cells will continue to be monitored under a separate long-term follow-up protocol for up to 15 years after JCAR017 infusion as per competent authority guidelines.

Arms:
arm 1: None

Interventions: intervention 1: JCAR017
Intervention descriptions: intervention 1: Specified dose on specified days

Protocol document:
Prot_SAP_000.pdf: 
Official Title of Study: 
A Phase 2, Single-arm, Multi-center Trial to Determine the Efficacy and Safety of JCAR017 in Subjects 
With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or With Other Aggressive B-Cell 
Malignancies 
 
NCT Number: NCT03484702 
Document Date (Date in which document was last revised): 12 August 2021 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
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CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional 
review board. The information contained in this document is regarded as 
confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by 
law or regulations. Persons to whom the information is disclosed must be 
informed that the information is confidential and may not be further 
disclosed by them. 
 
 
A PHASE 2, SINGLE-ARM, MULTI-COHORT, MULTI- 
CENTER TRIAL TO DETERMINE THE EFFICACY AND 
SAFETY OF JCAR017 IN ADULT SUBJECTS WITH 
AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA 
(TRANSCEND WORLD) 
 
 
PROTOCOL NUMBER: 
DATE FINAL: 
JCAR017-BCM-001 
24 Apr 2017 
DATE AMENDMENT 1: 
08 Jan 2018 
DATE AMENDMENT 2: 
28 Dec 2018 
DATE AMENDMENT 3: 
21 Nov 2019 
DATE AMENDMENT 4: 
16 Nov 2020 
DATE AMENDMENT 5: 
12 Aug 2021 
EudraCT NUMBER: 
2017-000106-38 
IND NUMBER: 
Not applicable 
SPONSOR NAME/ ADDRESS: 
Celgene Corporation 
86 Morris Avenue 
Summit, NJ 07901 
 
 
 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
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MEDICAL MONITOR AND EMERGENCY CONTACT INFORMATION 
 
 
Contact Information: 
Name: 
Title: 
Address: Route de Perreux 1, 2017 Boudry, Switzerland 
Phone: 
E-mail: 
Note: The back-up 24-hour global emergency contact call center should only be used if you 
are not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
 
Back-up 24-hour Global Emergency Contact Call Center: 


JCAR017 
Protocol JCAR017-BCM-001 
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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
 
 
See appended electronic signature page 
Signature of Celgene Therapeutic Area Head 
dd mmm yyyy 
Printed Name of Celgene Therapeutic Area Head and Title 
By my signature, I indicate I have reviewed this protocol and find its content to be 
acceptable. 


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Protocol JCAR017-BCM-001 
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
 
Signature of Site Principal Investigator 
dd mmm yyyy 
Printed Name of Site Principal Investigator 
Institution Name: 
 
By my signature, I agree to personally supervise the conduct of this study at my study 
site and to ensure its conduct is in compliance with the protocol, informed consent, 
Institutional Review Board (IRB)/Ethics Committee (EC) procedures, instructions from 
Celgene representatives, the Declaration of Helsinki, International Council for 
Harmonisation (ICH) Good Clinical Practices Guidelines, and local regulations 
governing the conduct of clinical studies. 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
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PROTOCOL SUMMARY 
Study Title 
A Phase 2, Single-arm, Multi-cohort, Multi-center Trial to Determine the Efficacy and Safety of 
JCAR017 in Adult Subjects with Aggressive B-Cell Non-Hodgkin Lymphoma 
Indication 
Aggressive B-cell non-Hodgkin lymphoma (B-NHL) 
Objectives 
Primary Objectives 
Cohorts 1, 2, 3, 4, and 5 
• Determine the efficacy, defined as overall response rate (ORR), of JCAR017 in 
subjects with aggressive B-cell non-Hodgkin lymphoma 
Cohort 7 
• Evaluate the safety of JCAR017 treatment in subjects intended to be treated as 
outpatients 
Secondary Objectives 
• Evaluate the safety and feasibility of administering JCAR017 (Cohorts 1, 2, 3, 4, and 
5) 
• To determine the efficacy, defined as ORR of JCAR017 in subjects intended to be 
treated as outpatients (Cohort 7) 
• Evaluate other measures of efficacy of JCAR017 (eg, complete response rate [CRR], 
event-free survival [EFS], progression-free survival [PFS], overall survival [OS], 
duration of response [DOR]) 
• Characterize the pharmacokinetic (PK) profile of JCAR017 in the peripheral blood 
measured using quantitative polymerase chain reaction (qPCR) detection for the 
JCAR017 vector sequence 
• Describe changes in health-related quality of life (HRQoL) using global health/QoL, 
fatigue, physical and cognitive functioning subscales of the European Organisation 
for Research and Treatment of Cancer – Quality of Life C30 questionnaire (EORTC 
QLQ-C30) and the Functional Assessment of Cancer Therapy-Lymphoma 
“Additional concerns” subscale (FACT-LymS) 
Study Design 
Study JCAR017-BCM-001 is a single-arm, multi-cohort, multi-center, Phase 2 study to 
determine the efficacy and safety of JCAR017 in subjects with aggressive B-cell NHL (B-NHL). 
Approximately 116 subjects will be enrolled into one of 6 cohorts as listed below: 
• Cohort 1: Subjects with diffuse large B-cell lymphoma (DLBCL) not otherwise 
specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B- 
cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL 


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histology [HGBL]) and follicular lymphoma Grade 3B (FL3B) per World Health 
Organization (WHO) 2016 classification (Swerdlow, 2016), after ≥ 2 lines of 
therapy*, including an anthracycline and rituximab (or other CD20-targeted agent) 
• Cohort 2: Transplant not eligible (TNE) subjects with DLBCL NOS (de novo or 
tFL), HGBL and FL3B per WHO 2016 classification, who failed first line therapy*, 
including an anthracycline and rituximab (or other CD20-targeted agent) 
− Transplant not eligible subjects will include those who are deemed ineligible for 
high-dose chemotherapy and HSCT due to age, performance status or 
comorbidity, while also having adequate organ function for CAR T cell treatment. 
At the very least, subjects have to meet one of the following criteria: 
a) Age ≥ 70 years 
b) ECOG performance status ≥ 2 
c) Impaired pulmonary function (diffusion capacity of carbon monoxide [DLCO] 
≤ 60%, adjusted for hemoglobin concentration using the Dinakara equation) 
d) Impaired cardiac function (left ventricular ejection fraction [LVEF] < 50%) 
e) Impaired renal function (creatinine clearance [CrCl] < 60 mL/min) 
f) Impaired hepatic function (aspartate aminotransferase [AST] / alanine 
aminotransferase [ALT] > 2 x upper limit of normal [ULN], bilirubin ≥ 2 
mg/dL or cirrhosis Child-Pugh B or C) 
• Cohort 3 (Japan only): Subjects meeting eligibility criteria for either Cohort 1 or 2 
• Cohort 4: Subjects with newly diagnosed HGBL. Subjects must be eligible for 
anthracycline and rituximab (or other CD20-targeted agent)-containing regimen as 
induction prior to consolidation with JCAR017** 
• Cohort 5: Subjects with primary central nervous system lymphoma (PCNSL), who 
failed first line therapy with high-dose chemotherapy (HDCT) and autologous stem 
cell transplantation (ASCT), or who failed to proceed to HDCT and ASCT due to 
failure of Peripheral blood stem cell (PBSC) mobilization or insufficient response at 
the completion of induction therapy with high-dose methotrexate-based 
polychemotherapy regimen (eg, high dose methotrexate, high dose cytarabine, 
rituximab and thiotepa [MATRix regimen]) 
• Cohort 6: (REMOVED) 
• Cohort 7: Subjects meeting eligibility criteria for Cohort 1 and suitable for outpatient 
treatment*** 
* For subjects with transformed disease, the subject should have had at least 2 lines of 
systemic therapy for his/her transformed disease (ie, DLBCL) for Cohort 1 and 1 line for 
Cohort 2 to be eligible. Lines of therapy do not include those given for a previously indolent 
condition (ie, follicular lymphoma). Subjects do NOT have to have anthracycline for their 
DLBCL if received for indolent disease. 


JCAR017 
Protocol JCAR017-BCM-001 
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** For subjects already undergoing anthracycline and rituximab-containing regimen, 
eligibility is to be discussed with the Medical Monitor. Subjects with complete metabolic 
response after 2 cycles of induction will proceed with JCAR017 infusion only at time of 
relapse, if applicable. 
*** Subjects must meet the conditions for outpatient treatment and monitoring as outlined in 
the Outpatient Administration and Monitoring Guidance for Lisocabtagene Maraleucel. 
Note: Subjects with secondary central nervous system (CNS) lymphoma involvement may 
enroll in Cohorts 1 to 4 and 7; subjects with PCNSL are eligible for Cohort 5. Subject 
selection must consider clinical risk factors for severe adverse events (AEs) and alternative 
treatment options. Subjects should only be enrolled if the Investigator considers the potential 
benefit outweighs the risk for the subject. For Cohort 5 and to not compromise safety, subject 
selection has been restricted to those fit enough to be considered for HDCT and ASCT as 
their prior therapy. 
The first 3 subjects in Europe in Cohort 1 will be treated with a minimum interval of 14 days 
between JCAR017 infusions and assessed for acute safety 28 days after the third subject has 
received JCAR017 infusion. In addition, the product characteristics of the JCAR017 cell product 
manufactured with processing steps in Europe will be evaluated. If criteria for safety and 
feasibility are met, Cohort 1 will continue enrollment without gating and additional Cohorts 2, 4, 
5 and 7 may be opened at Celgene’s discretion. A minimum of 14 days treatment interval will 
also apply to all subjects treated in Cohort 5. 
The first 10 subjects treated with JCAR017 in Europe must be hospitalized for a minimum of 14 
days after JCAR017 infusion, unless otherwise recommended by a local authority. Experience to 
date with JCAR017 from the Juno TRANSCEND NHL 001 (017001) study suggests that 
outpatient administration of JCAR017 can be provided safely without compromising the 
subject’s safety when appropriate education is provided and hospital admission is done upon 
symptoms of toxicity. Outpatient infusion of JCAR017 was associated with a 68% decrease in 
hospital length of stay (Palomba, 2018). Selected countries/sites will participate in the dedicated 
outpatient cohort. In order to enroll subjects in Cohort 7, sites must have treated at least 3 
DLBCL subjects with CD19-targeted CAR T cell therapy, and must have a suitable 
infrastructure to allow for outpatient treatment and monitoring as outlined in the Outpatient 
Administration and Monitoring Guidance for Lisocabtagene Maraleucel. 
Safety data will be reviewed on an ongoing basis. An early safety assessment will be performed 
28 days after JCAR017 is administered to the 10th subject treated in Europe. Enrollment will be 
halted if the observed mortality rate is > 30%, irrespective of causality, or if > 50% of subjects 
who undergo leukapheresis fail to have a satisfactory cell product available for infusion. 
In addition, an early safety assessment will be performed 28 days after JCAR017 is administered 
to the 10th subject treated in Cohort 2. Enrollment into Cohort 2 will be halted if the observed 
mortality rate within 28 days post infusion is > 30% (excluding death related to disease 
progression or relapse). 
The first 3 subjects in Japan will be treated with a minimum interval of 14 days between 
JCAR017 infusions and assessed for acute safety 28 days after the third subject has received 
JCAR017 infusion. In addition, the first 10 subjects treated with JCAR017 in Japan must be 
hospitalized for a minimum of 14 days after JCAR017 infusion. The acute and subacute toxicity 


JCAR017 
Protocol JCAR017-BCM-001 
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profile of JCAR017 cell product manufactured entirely at the current manufacturing site in the 
United States (US) has already been established in subjects with relapsed/refractory (r/r) B-NHL 
with good tolerability observed in subjects with DLBCL (Abramson, 2018). 
In addition, a staggered dosing approach will also be utilized for all new sites (Europe and Japan) 
without prior experience of administering CAR T cell therapies as follows: 
• 1st subject infusion, wait 14 days 
• 2nd subject infusion, wait 14 days 
Following completion of the site-staggered enrollment approach for the first 2 subjects, the site 
may proceed with subject enrollment as communicated by Celgene. 
Prior to initiation of any study procedure (screening period), subjects must provide informed 
consent. Once enrolled and during the pretreatment period, subjects will undergo leukapheresis 
to enable JCAR017 cell product generation. Upon successful JCAR017 cell product generation, 
subjects will enter the treatment period and receive lymphodepleting (LD) chemotherapy 
followed by infusion of JCAR017, 2 to 7 days after completion of LD chemotherapy. JCAR017 
will be administered at a dose of 100 x 106 JCAR017-positive transfected viable T cells (CAR+ 
T cells). 
After treatment with JCAR017, subjects will enter the post-treatment period. A first response 
assessment will be performed 28 days after JCAR017 infusion. Subjects will be followed for 2 
years after their JCAR017 infusion for safety, disease status, survival and health-related quality 
of life and utility values measured using EORTC QLQ-C30 and EQ-5D-5L questionnaires and 
the FACT-LymS. 
In addition, when feasible, all subjects will be invited to participate in interviews during their 
participation in the study to document their experience with JCAR017. 
Delayed adverse events following exposure to gene modified T cells will be assessed and long- 
term persistence of these modified T cells, including vector integration sites as well as the 
generation of replication competent retrovirus will continue to be monitored under a separate 
Long-term follow-up (LTFU) protocol for up to 15 years after JCAR017 infusion as per 
competent authority guidelines. 
The decision to discontinue a subject from the study is the responsibility of the Investigator or 
designee. Celgene will not delay or refuse this decision. However, prior to discontinuing a 
subject, the Investigator should contact the Medical Monitor and forward appropriate supporting 
documents for review and discussion. 
Study Population 
This study will enroll adult subjects in Europe and Japan with DLBCL NOS (de novo or tFL), 
HGBL, FL3B, and PCNSL. Subjects with secondary CNS involvement are allowed. 
Length of Study 
This study will enroll over approximately 40 months and will consist of 3 periods: 
• The pretreatment period will consist of screening for eligibility, leukapheresis and a 
pretreatment evaluation (prior to LD chemotherapy) 


JCAR017 
Protocol JCAR017-BCM-001 
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• The treatment period will start with LD chemotherapy, followed by JCAR017 
infusion 2 to 7 days after completion of LD chemotherapy. A first response 
evaluation will be performed at approximately 28 days after JCAR017 infusion 
• The post-treatment period will consist of further efficacy and safety follow-up visits 
at approximately 2, 3 (at 4 months for Cohort 5), 6, 9, 12, 18 and 24 months after 
JCAR017 infusion 
The End of Trial is defined as either the date of the last visit of the last subject completing the 
post-treatment follow-up of this study or the date when the last subject enters the LTFU study, or 
the date of receipt of the last data point from the last subject that is required for primary, 
secondary and/or exploratory analysis, as pre-specified in the protocol, whichever is the later 
date. 
Study Procedures and Treatments 
Following enrollment in the study, a leukapheresis collection will be performed on each subject 
to obtain a sufficient quantity of peripheral blood mononuclear cells (PBMCs) for the production 
of the JCAR017 cell product. 
If necessary, anticancer treatment is allowed for disease control while JCAR017 is being 
manufactured (ie, after leukapheresis and prior to LD chemotherapy). After anticancer treatment 
the subject must continue to have positron emission tomography (PET)-positive disease and meet 
eligibility criteria pertaining to adequate organ function, active infections, pregnancy, and 
washout of prior therapy before initiation of LD chemotherapy. 
Subjects will receive 3 days of fludarabine intravenously (IV) (30 mg/m2/day) and 
cyclophosphamide IV (300 mg/m2/day) for LD chemotherapy. Two to 7 days after completion of 
LD chemotherapy, JCAR017 will be administered by IV infusion at a dose of 100 x 106 
JCAR017-positive transfected viable T cells (CAR+ T cells) as a single dose on Day 1. The 
JCAR017 investigational drug product is provided as 2 individually formulated CD8+CAR+ and 
CD4+CAR + frozen T cell suspensions in media containing dimethyl sulfoxide (DMSO) that are 
thawed and administered separately by IV infusion. 
Subjects must be clinically stable and must have recovered from prior toxicities, to receive LD 
chemotherapy and proceed to JCAR017 infusion. Neither LD chemotherapy nor JCAR017 
treatment should be administered if there is a worsening of performance status to ECOG 2, rapid 
clinical deterioration, or evidence of rapidly progressive disease. Note: subjects who are 
transplant not eligible or have PCNSL may have ECOG 2, however, must be clinically stable, 
recover from prior toxicities, and not have evidence of rapidly progressive disease or rapid 
clinical deterioration prior to receiving LD chemotherapy or JCAR017 infusion. 
Overview of Key Efficacy Assessments 
• DLBCL, FL3B: Efficacy response will be assessed according to the 
“Recommendations for Initial Evaluation, Staging, and Response Assessment of 
Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification” (Cheson, 2014) 
based on radiographic tumor assessments. Subjects will have radiographic disease 
assessment by PET and/or computed tomography (CT)/ magnetic resonance imaging 
(MRI) scans at pretreatment evaluation and approximately 1, 3, 6, 9, 12, 18 and 
24 months following JCAR017 infusion or until progressive disease or relapse 


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Protocol JCAR017-BCM-001 
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− For subjects with secondary CNS involvement repeat cerebrospinal fluid (CSF) 
evaluation together with brain MRI and PET-CT when relevant 
• PCNSL: Efficacy response will be assessed according to the “Report of an 
International Workshop to Standardize Baseline Evaluation and Response Criteria for 
Primary CNS Lymphoma” (Abrey, 2005) at pretreatment evaluation and 
approximately 1, 2, 4, 6, 9, 12, 18 and 24 months based on brain MRI and CSF 
examination. For subjects without CSF involvement, repeated evaluation is not 
required in absence of interval symptoms suggestive of leptomeningeal 
dissemination. PET-CT does not need to be repeated in the absence of systemic 
disease at baseline or suspicion of systemic PD. Ophthalmologic evaluation is 
completed at screening to exclude ocular lymphoma and does not need to be repeated 
unless symptoms occur. 
Overview of Key Safety Assessments 
Safety will be monitored via the following assessments at each visit: 
• Physical examination, including performance status (PS) 
• Laboratory evaluations 
• Neurologic examination 
• Adverse event (including serious adverse event [SAE]) monitoring and collection, 
including cytokine release syndrome (CRS) evaluation and neurotoxicity 
Overview of Key Patient-Reported Outcome Assessments 
Patient-reported outcomes (PROs) will be measured via the following assessments at each visit: 
• EORTC QLQ-C30 
• EQ-5D-5L 
• FACT-LymS 
All subjects will be required to complete the above questionnaires. 
Where feasible, patient interviews will be used to capture the experience of JCAR017 therapy 
from a subject perspective. 
Overview of Key Resource Use Data Capture 
The time that subjects spend in hospital expressed in days spent in intensive care unit 
(ICU)/Non-ICU will be captured. 
Statistical Methods 
A formal interim analysis with the first 10 subjects treated with JCAR017 in Cohort 1 being 
followed for at least 3 months after JCAR017 infusion to test the superiority of JCAR017 will be 
performed. 
Data from all sites will be combined for the final analysis for each cohort. Results will be 
presented using descriptive statistics. 


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Efficacy information will be summarized separately per cohort. Safety information will be 
analyzed per cohort and across cohorts. PK information will be combined for all subjects across 
cohorts. 
The study will be conducted in compliance with International Council for Harmonisation (ICH) 
Good Clinical Practices (GCPs). 


JCAR017 
Protocol JCAR017-BCM-001 
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TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................................... 1 
PROTOCOL SUMMARY ............................................................................................................... 5 
1. 
INTRODUCTION....................................................................................................... 21 
1.1. 
Disease Background .................................................................................................... 21 
1.1.1. 
Non-Hodgkin Lymphoma ........................................................................................... 21 
1.1.1.1. 
High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 
Rearrangements with DLBCL Histology .................................................................... 22 
1.1.1.2. 
Primary Central Nervous System Lymphoma............................................................. 23 
1.2. 
Compound Background .............................................................................................. 24 
1.2.1. 
CD19 as a Therapeutic Target ..................................................................................... 24 
1.2.2. 
CD19-Targeted Chimeric Antigen Receptors ............................................................. 24 
1.2.3. 
JCAR017 Investigational Drug Product ...................................................................... 25 
1.2.4. 
Clinical Experience with JCAR017 and Related CAR T Cell Products ..................... 25 
1.3. 
Rationale ..................................................................................................................... 27 
1.3.1. 
Study Rationale and Purpose ...................................................................................... 27 
1.3.2. 
Lymphodepleting Chemotherapy Rationale ................................................................ 27 
1.3.3. 
Rationale for JCAR017 Dose Selection ...................................................................... 28 
1.3.4. 
Rationale for Pharmacodynamics and Potential Predictive Biomarkers ..................... 28 
2. 
STUDY OBJECTIVES AND ENDPOINTS .............................................................. 31 
3. 
OVERALL STUDY DESIGN .................................................................................... 36 
3.1. 
Study Design ............................................................................................................... 36 
3.2. 
Stopping Rules ............................................................................................................ 39 
3.2.1. 
Criteria for Pausing or Stopping the Study ................................................................. 39 
3.2.2. 
Criteria for Pausing or Stopping Cohort 7 .................................................................. 39 
3.3. 
Study Duration for Subjects ........................................................................................ 40 
3.4. 
End of Trial ................................................................................................................. 40 
4. 
STUDY POPULATION ............................................................................................. 43 
4.1. 
Number of Subjects ..................................................................................................... 43 
4.2. 
Inclusion Criteria ......................................................................................................... 43 
4.3. 
Exclusion Criteria ....................................................................................................... 46 
5. 
TABLE OF EVENTS ................................................................................................. 49 
6. 
PROCEDURES ........................................................................................................... 56 


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6.1. 
Pretreatment Period .................................................................................................... 56 
6.1.1. 
Screening .................................................................................................................... 56 
6.1.2. 
Leukapheresis (approximately 35 days prior to JCAR017 infusion) ......................... 57 
6.1.3. 
Anticancer Treatments between Leukapheresis and Lymphodepleting 
Chemotherapy ............................................................................................................ 59 
6.1.4. 
Pretreatment Evaluation (following enrollment and within 7 days prior to 
lymphodepleting chemotherapy) ................................................................................ 59 
6.2. 
Treatment Period ........................................................................................................ 61 
6.2.1. 
Lymphodepleting Chemotherapy (start 5 to 10 days prior to JCAR017 
infusion) ..................................................................................................................... 61 
6.2.2. 
JCAR017 Administration: Day 1 ............................................................................... 61 
6.2.3. 
Days 2 and 3 ............................................................................................................... 63 
6.2.4. 
Day 4 (+1 day) ........................................................................................................... 63 
6.2.5. 
Day 8 (±1 day) ........................................................................................................... 64 
6.2.6. 
Day 11 (±1 day) ......................................................................................................... 64 
6.2.7. 
Days 15, 22, and 29 (±2 days) .................................................................................... 65 
6.3. 
Post-Treatment Period (Follow-up) ............................................................................ 66 
6.3.1. 
Unscheduled Evaluations ........................................................................................... 67 
6.3.2. 
Assessments upon Progressive Disease ..................................................................... 68 
6.3.3. 
Assessment upon Complete Response ....................................................................... 68 
6.3.4. 
Assessments at Time of Death ................................................................................... 68 
6.3.5. 
Early Withdrawal ....................................................................................................... 69 
6.3.6. 
Survival Follow-Up .................................................................................................... 69 
6.3.7. 
Long-Term Follow-Up ............................................................................................... 69 
6.4. 
Safety Assessments .................................................................................................... 69 
6.4.1. 
Physical Examination ................................................................................................. 69 
6.4.2. 
Vital Signs .................................................................................................................. 69 
6.4.3. 
Height and Weight ..................................................................................................... 69 
6.4.4. 
Routine Neurologic and Mini Mental State Examinations ......................................... 69 
6.4.5. 
Cerebrospinal Fluid Assessment and Central Nervous System Symptom 
Assessment ................................................................................................................. 70 
6.4.6. 
Eastern Cooperative Oncology Group Performance Status ....................................... 70 
6.4.7. 
Echocardiogram and Multigated Acquisition Scan .................................................... 70 
6.4.8. 
Electrocardiogram ...................................................................................................... 70 


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6.4.9. 
Replication-Competent Lentivirus Testing ................................................................. 70 
6.4.10. 
Persistent Vector Sequence Monitoring ...................................................................... 71 
6.4.11. 
Clinical Laboratory Evaluations .................................................................................. 71 
6.5. 
Efficacy Assessment ................................................................................................... 71 
6.5.1. 
Pseudoprogression ....................................................................................................... 72 
6.5.2. 
Independent Review Committee ................................................................................. 72 
6.6. 
Pharmacokinetics ........................................................................................................ 72 
6.7. 
Biomarkers, Pharmacodynamics, Pharmacogenomics ................................................ 72 
6.7.1. 
Immunogenicity Assessments ..................................................................................... 72 
6.7.2. 
Biomarker Assessments .............................................................................................. 72 
6.8. 
Patient-Reported Outcomes......................................................................................... 74 
6.8.1. 
EORTC QLQ-C30 ...................................................................................................... 74 
6.8.2. 
EQ-5D-5L ................................................................................................................... 74 
6.8.3. 
FACT-LymS ............................................................................................................... 75 
6.8.4. 
Patient Interviews ........................................................................................................ 75 
6.9. 
Hospital Resource Utilization ..................................................................................... 77 
7. 
DESCRIPTION OF STUDY TREATMENTS ........................................................... 78 
7.1. 
Lymphodepleting Chemotherapy ................................................................................ 78 
7.2. 
Description of Investigational Product ........................................................................ 78 
7.2.1. 
JCAR017 ..................................................................................................................... 78 
7.3. 
Treatment Administration and Schedule ..................................................................... 78 
7.3.1. 
Lymphodepleting Chemotherapy ................................................................................ 78 
7.3.2. 
JCAR017 Premedication ............................................................................................. 79 
7.3.3. 
JCAR017 Preparation and Cell Thawing .................................................................... 79 
7.3.4. 
JCAR017 Administration ............................................................................................ 79 
7.3.5. 
Protocol Product Deviation Plan ................................................................................. 79 
7.3.6. 
Exception Use of Non-conforming Product ................................................................ 79 
7.3.7. 
Overdose ..................................................................................................................... 80 
7.4. 
Method of Treatment Assignment............................................................................... 80 
7.5. 
Packaging and Labeling .............................................................................................. 80 
7.5.1. 
Product Tracking ......................................................................................................... 80 
7.5.2. 
Product Packaging and Labeling ................................................................................. 80 
7.5.3. 
Cell Product Supply and Storage ................................................................................ 81 


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7.6. 
Investigational Product Accountability and Disposal ................................................. 81 
7.6.1. 
Accountability Procedures .......................................................................................... 81 
7.6.2. 
Drug Disposal and Destruction ................................................................................... 81 
7.7. 
Investigational Product Compliance ........................................................................... 81 
8. 
CONCOMITANT MEDICATIONS AND PROCEDURES ...................................... 82 
8.1. 
Permitted Concomitant Medications and Procedures ................................................. 82 
8.2. 
Prohibited Concomitant Medications and Procedures ................................................ 82 
8.3. 
Concomitant Medications and Procedures .................................................................. 83 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 85 
9.1. 
Overview ..................................................................................................................... 85 
9.2. 
Study Population Definitions ...................................................................................... 85 
9.2.1. 
Screened Set ................................................................................................................ 85 
9.2.2. 
Enrolled Set ................................................................................................................. 85 
9.2.3. 
Leukapheresed Set ...................................................................................................... 85 
9.2.4. 
JCAR017-Treated Set ................................................................................................. 85 
9.2.5. 
Efficacy Evaluable Set ................................................................................................ 85 
9.2.6. 
qPCR Pharmacokinetic Analysis Set .......................................................................... 85 
9.2.7. 
Flow Cytometry Pharmacokinetic Analysis Set .......................................................... 86 
9.2.8. 
Patient-Reported Outcome Analysis Set ..................................................................... 86 
9.2.9. 
Population Analyses .................................................................................................... 86 
9.3. 
Sample Size and Power Considerations ...................................................................... 86 
9.3.1. 
Cohort 1 ...................................................................................................................... 86 
9.3.2. 
Cohort 2 ...................................................................................................................... 86 
9.3.3. 
Cohort 3 (Japan only) .................................................................................................. 87 
9.3.4. 
Cohort 7 ...................................................................................................................... 87 
9.3.5. 
Gated Cohorts ............................................................................................................. 88 
9.4. 
Background and Demographic Characteristics ........................................................... 88 
9.5. 
Subject Disposition ..................................................................................................... 88 
9.6. 
Efficacy Analysis ........................................................................................................ 88 
9.6.1. 
General Consideration ................................................................................................. 88 
9.6.2. 
Primary Endpoint ........................................................................................................ 89 
9.6.3. 
Secondary Efficacy Endpoints .................................................................................... 89 
9.6.4. 
Subgroup Analyses...................................................................................................... 90 


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9.7. 
Safety Analysis ........................................................................................................... 91 
9.7.1. 
Adverse Events ........................................................................................................... 91 
9.7.2. 
Definition of Treatment-emergent Adverse Event ...................................................... 92 
9.7.3. 
Summary of Adverse Events ....................................................................................... 92 
9.8. 
Laboratory Evaluations ............................................................................................... 93 
9.8.1. 
Numeric Laboratory Results ....................................................................................... 93 
9.8.2. 
Graded Laboratory Values .......................................................................................... 93 
9.8.3. 
Summaries of Laboratory Abnormalities .................................................................... 93 
9.9. 
Other Topics ................................................................................................................ 93 
9.9.1. 
Data Safety Monitoring Board .................................................................................... 93 
9.9.2. 
Scientific Steering Committee .................................................................................... 94 
9.9.3. 
Exploratory Analysis ................................................................................................... 94 
10. 
ADVERSE EVENTS .................................................................................................. 96 
10.1. 
Monitoring, Recording and Reporting of Adverse Events ......................................... 96 
10.2. 
Evaluation of Adverse Events ..................................................................................... 98 
10.2.1. 
Seriousness .................................................................................................................. 98 
10.2.2. 
Severity and Intensity .................................................................................................. 99 
10.2.3. 
Causality .................................................................................................................... 100 
10.2.4. 
Duration .................................................................................................................... 100 
10.2.5. 
Action Taken ............................................................................................................. 100 
10.2.6. 
Outcome .................................................................................................................... 100 
10.3. 
Abnormal Laboratory Values .................................................................................... 100 
10.4. 
Pregnancy .................................................................................................................. 101 
10.4.1. 
Females of Childbearing Potential ............................................................................ 101 
10.4.2. 
Male Subjects ............................................................................................................ 101 
10.5. 
Reporting of Serious Adverse Events ....................................................................... 102 
10.5.1. 
Safety Queries ........................................................................................................... 102 
10.5.2. 
Death Reports ............................................................................................................ 102 
10.6. 
Expedited Reporting of Adverse Events ................................................................... 102 
10.7. 
Adverse Event of Special Interest ............................................................................. 103 
10.8. 
Potential Risks and Management of Treatment Toxicities ....................................... 103 
10.8.1. 
Management of Toxicities Associated with JCAR017 ............................................. 104 
10.8.1.1. 
Cytokine Release Syndrome ..................................................................................... 104 


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10.8.1.2. 
Fever ......................................................................................................................... 104 
10.8.1.3. 
Cytopenias ................................................................................................................. 105 
10.8.1.4. 
Infections ................................................................................................................... 105 
10.8.1.5. 
Neurologic Toxicities ................................................................................................ 105 
10.8.1.6. 
Macrophage Activation Syndrome ............................................................................ 105 
10.8.1.7. 
Infusion Reactions ..................................................................................................... 106 
10.8.1.8. 
Tumor Lysis Syndrome ............................................................................................. 106 
10.8.1.9. 
B-Cell Aplasia ........................................................................................................... 106 
10.8.1.10. Graft-Versus-Host Disease ....................................................................................... 107 
10.8.1.11. Uncontrolled T Cell Proliferation .............................................................................. 107 
10.8.1.12. Replication-Competent Lentivirus, Clonality and Insertional Oncogenesis ............. 107 
10.8.1.13. Risks Associated with Lymphodepleting Chemotherapy ......................................... 107 
10.8.1.14. New Malignancies ..................................................................................................... 108 
11. 
DISCONTINUATIONS ............................................................................................ 109 
11.1. 
Treatment Discontinuation ........................................................................................ 109 
11.2. 
Study Discontinuation ............................................................................................... 109 
12. 
EMERGENCY PROCEDURES ............................................................................... 110 
12.1. 
Emergency Contact ................................................................................................... 110 
12.2. 
Emergency Identification of Investigational Products .............................................. 110 
13. 
REGULATORY CONSIDERATIONS .................................................................... 111 
13.1. 
Good Clinical Practice .............................................................................................. 111 
13.2. 
Investigator Responsibilities ..................................................................................... 111 
13.3. 
Subject Information and Informed Consent .............................................................. 112 
13.4. 
Confidentiality ........................................................................................................... 112 
13.5. 
Protocol Amendments ............................................................................................... 112 
13.6. 
Institutional Review Board and Independent Ethics Committee Review and 
Approval ................................................................................................................... 112 
13.7. 
Ongoing Information for Institutional Review Board and Ethics Committee .......... 113 
13.8. 
Termination of the Study .......................................................................................... 113 
14. 
DATA HANDLING AND RECORDKEEPING ...................................................... 114 
14.1. 
Data and Documents ................................................................................................. 114 
14.2. 
Data Management ..................................................................................................... 114 
14.3. 
Record Retention ....................................................................................................... 114 


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE ........................................ 116 
15.1. 
Study Monitoring and Source Data Verification ....................................................... 116 
15.2. 
Audits and Inspections .............................................................................................. 116 
16. 
PUBLICATIONS ...................................................................................................... 117 
17. 
REFERENCES .......................................................................................................... 118 
APPENDIX A. TABLE OF ABBREVIATIONS...................................................................... 125 
APPENDIX B. PERFORMANCE STATUS BY EASTERN COOPERATIVE 
ONCOLOGY GROUP SCALE ................................................................................ 132 
APPENDIX C. RECOMMENDATIONS FOR INITIAL EVALUATION, STAGING, 
AND RESPONSE ASSESSMENT OF HODGKIN AND NON-HODGKIN 
LYMPHOMA: THE LUGANO CLASSIFICATION............................................... 133 
APPENDIX D. MINI MENTAL STATE EXAMINATION .................................................... 137 
APPENDIX E. CLINICAL LABORATORY EVALUATIONS .............................................. 141 
APPENDIX F. COCKCROFT-GAULT EQUATION FOR CALCULATING 
ESTIMATED CREATININE CLEARANCE .......................................................... 142 
APPENDIX G. HCT-CI SCORE CALCULATOR ................................................................... 143 
APPENDIX H. FRAILTY SCALE ........................................................................................... 145 
APPENDIX I. PATIENT-REPORTED OUTCOMES: EORTC QLQ C-30 ............................ 147 
APPENDIX J. PATIENT-REPORTED OUTCOMES: EQ-5D-5L .......................................... 149 
APPENDIX K. PATIENT-REPORTED OUTCOMES: FACT-LYMS ................................... 151 
APPENDIX L. CAIRO-BISHOP DEFINITIONS OF TUMOR LYSIS SYNDROME ........... 152 
APPENDIX M. JCAR017 MANAGEMENT GUIDELINES FOR CYTOKINE 
RELEASE SYNDROME AND NEUROLOGIC TOXICITIES (V3.2) ................... 154 


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LIST OF TABLES 
Table 1: 
Study Objectives ........................................................................................................ 31 
Table 2: 
Study Endpoints ......................................................................................................... 33 
Table 3: 
Safety Monitoring Boundaries for Cohort 7 Based on Thall and Simon 
(Thall, 1994)............................................................................................................... 40 
Table 4: 
Table of Events .......................................................................................................... 49 
Table 5: 
Washout Periods Prior to Leukapheresis and Prior to Lymphodepleting 
Chemotherapy ............................................................................................................ 58 
Table 6: 
Exploratory Biomarkers Sampling ............................................................................. 73 
Table 7: 
Table of Events, Patient Interviews ............................................................................ 77 
Table 8: 
Example Rates (± 95% Confidence Intervals) ........................................................... 88 
Table 9: 
Recording Periods for Adverse Events ...................................................................... 97 


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LIST OF FIGURES 
Figure 1: 
Overall Study Design .................................................................................................. 41 
Figure 2: 
Study Schematic .......................................................................................................... 42 


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1. 
INTRODUCTION 
1.1. 
Disease Background 
1.1.1. 
Non-Hodgkin Lymphoma 
Non-Hodgkin lymphomas (NHL) comprise a heterogeneous group of malignancies. Within 
Europe, the incidence of NHL is approximately 49,533 with a mortality of 20,347 (Ferlay, 2015) 
and within the United States (US), the incidence and mortality is approximately 72,580 and 
20,150, respectively (Siegel, 2016). Non-Hodgkin lymphomas are classified according to the 
current World Health Organization (WHO) classification (Swerdlow, 2016) into immature 
lymphoid neoplasms, mature B-cell neoplasms, T cell and natural killer (NK) cell neoplasms, 
and post-transplant lymphoproliferative disorders. Mature B-cell lymphomas are further 
classified into indolent lymphomas (eg, multiple myeloma, chronic lymphocytic leukemia 
[CLL]) and aggressive lymphomas (eg, diffuse large B-cell lymphoma [DLBCL]). 
Diffuse large B-cell lymphoma is the most frequent lymphoma subtype, representing 
approximately 30% of all NHL. Diffuse large B-cell lymphoma can develop de novo or 
secondary to transformation of an indolent NHL. Estimated incidence in the European Union 
(EU) is 3 to 4/100,000/year, increasing with age from 0.3/100,000/year (35 to 39 years) to 
26.6/100,000/year (80 to 84 years) (Tilly, 2012). About 10,000 deaths per year are due to 
DLBCL in the US (National Cancer Institute). Most patients with localized DLBCL can be cured 
with conventional combination immunochemo- or combined-modality therapy (Tilly, 2015). For 
patients with advanced-stage disease, the majority of patients can be cured with doxorubicin- 
based combination chemotherapy and rituximab (eg, rituximab, cyclophosphamide, doxorubicin 
hydrochloride, vincristine sulfate, prednisone [R-CHOP]). Prognosis depends on individual risk 
factors. The International Prognostic Index (IPI) for aggressive NHL (diffuse large cell 
lymphoma) includes five significant risk factors prognostic of overall survival (OS): Patient age, 
serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) 
performance status, disease stage, and extranodal involvement. Patients with ≥ 2 risk factors after 
age-adjustment have a poor prognosis with a 5-year OS-rate of 21% to 46%. 
Despite overall improvement in outcomes of DLBCL, approximately one-third of patients will 
develop relapsed/refractory disease that remains a major cause of mortality. Refractory disease is 
defined as a < 50% decrease in lesion size or the appearance of new lesions. Relapsed disease 
reflects the (re)appearance of lesions after attainment of a partial or complete response (PR, CR) 
(Cheson, 2007). Relapsed/refractory patients have a poor prognosis due to lack of effective 
treatment options, particularly those who do not respond to second-line chemotherapy (median 
OS of 4.4 months) (Van Den Neste, 2016) and those who are transplant not eligible (TNE) after 
first line therapy. Elderly patients or patients with relevant organ dysfunction have typically been 
excluded in prospective trials exploring high-dose chemotherapy and stem cell transplant and 
evidence that this approach is better than conventional chemotherapy in this patient population 
remains to be demonstrated. The missing clear cut definitions of “not eligible for transplant” in 
the literature leads to highly individualized decision approaches among centers. To better 
describe nontransplant eligibility in this trial, Celgene and Juno jointly reached out to 
investigators in order to define criteria that are commonly used in the clinical setting to exclude 
patients from high-dose chemotherapy and stem cell transplant. These criteria are being included 
in the definition of the population to be enrolled in this study and study 017006 (PILOT), a study 


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being conducted in parallel in the US. Diffuse large B-cell lymphoma is a heterogeneous disease 
with several histological and molecular subtypes. The largest subgroup is DLBCL not otherwise 
specified (NOS). Molecular profiling by gene expression profiling (GEP) based on biologic 
similarity to normal stages of B-cell development (cell of origin [COO]) helped to further divide 
DLBCL into germinal center B-cell-like (GCB), activated B-cell-like (ABC) tumors, and 
primary mediastinal large B-cell lymphoma (PMBCL), a distinct clinical entity (Lenz, 2008). 
Immunohistochemistry (IHC) algorithms are clinically used to identify the COO and helped to 
identify ABC DLBCL as a high-risk subtype less likely to respond to standard 
immunochemotherapy. 
Despite follicular lymphoma being an indolent lymphoma type, follicular lymphoma Grade 3B 
(FL3B) is regarded as aggressive lymphoma. Clinical behavior is very similar to DLBCL and FL 
frequently undergoes histological transformation into DLBCL. Consequently, current guidelines 
recommend treating FL3B according to the DLBCL treatment algorithm (National 
Comprehensive Cancer Network [National Comprehensive Cancer Network, 2019]). These 
patients are generally treated with an anthracycline-based chemotherapy combined with 
rituximab (eg, R-CHOP) and have a similar prognosis to that of de novo DLBCL. 
1.1.1.1. 
High-grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 
Rearrangements with DLBCL Histology 
High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL 
histology (HGBL) per WHO 2016 classification (Swerdlow, 2016) now encompass the entity 
previously referred to as double-hit or triple-hit lymphoma (DHL/THL). High-grade B-cell 
lymphoma represents approximately 7% to 10% of de novo cases of DLBCL with very poor OS 
of ≤ 12 months when treated with R-CHOP (Rosenthal, 2017). 
This subset of HGBL has a poor prognosis when treated with standard chemoimmunotherapy 
and has increased risk of central nervous system (CNS) involvement and progression. 
Retrospective studies strongly suggest that aggressive induction regimens may confer a superior 
outcome. A multicenter retrospective analysis (Petrich, 2014) involving 311 patients with DHL 
treated with R-CHOP or intensive induction therapy, including dose-adjusted rituximab, 
etoposide, prednisolone, oncovin, cyclophosphamide, and hydroxydaunorubicin (R-EPOCH) 
regimen, fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (Hyper- 
CVAD) alternating with methotrexate and cytarabine (MA), or cyclophosphamide, vincristine, 
doxorubicin, high-dose methotrexate (CODOX-M)/ ifosfamide, etoposide and high-dose 
cytarabine (IVAC) showed the highest response rate for those treated with dose-adjusted R- 
EPOCH. Intensive induction was associated with improved progression free survival and 
improved overall survival in a multivariate analysis. The MD Anderson Cancer Center published 
a similar retrospective study involving 129 patients from their institution. In this study, CNS 
involvement occurred in 13% of patients. Patients with bone marrow involvement and poor 
performance status had the worst prognosis. Two-year event-free survival rates in patients who 
received R-CHOP, R-EPOCH, and R-HyperCVAD/MA were 25%, 67%, and 32%, respectively 
(Oki, 2014). Given the urgent need to improve prognosis for patients with HGBL, studies should 
embrace the concept of induction therapy followed by consolidation or maintenance therapy and 
explore novel treatment approaches in the front-line setting, a population with clear defined 
unmet medical need. 


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1.1.1.2. 
Primary Central Nervous System Lymphoma 
Primary central nervous system lymphoma (PCNSL) is defined as lymphoma involving the 
cerebral parenchyma, leptomeninges, eyes or spinal cord without evidence of systemic disease 
that occurs in immunocompetent patients. PCNSL represents 2%–3% of all brain tumours, and 
less than 1% of all NHLs. Most of the cases are DLBCLs and 10%–20% develop intraocular 
lesions but rarely disseminate systemically (Deckert, 2011). 
The International Extranodal Lymphoma Study Group (IELSG) has proposed a prognostic 
system for PCNSL based on the following prognostic factors: 
• Age > 60 years 
• Eastern Cooperative Oncology Group (ECOG) PS >1 
• Elevated serum LDH 
• Elevated cerebrospinal fluid (CSF) protein concentration 
• Tumor localization within the deep regions of the brain 
Based on the overall score, 3 categories have been defined as good risk (0–1), intermediate risk 
(2–3), and poor risk (4–5). 
The Memorial Sloan-Kettering Cancer Center prognostic model for PCNSL (Abrey, 2006) only 
requires age and clinical performance status to build 3 different risk groups: good risk (patients 
< 50 years), intermediate risk (patients ≥ 50 years and Karnofsky performance score [KPS] ≥ 70) 
and high risk (patients ≥ 50; KPS < 70). 
Historically, whole brain radiation therapy (WBRT) has been the standard treatment for PCNSL, 
and addition of immunochemotherapy to WBRT has improved significantly survival. Use of 
high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) has shown 
encouraging results in first line therapy of PCNSL with reduced neurotoxicity by avoiding 
WBRT and improving outcome (Illerhaus, 2016). Despite advances in initial treatment, up to 
half of patients relapse, and 10% to 15% of patients have primary refractory disease. Patients 
with primary refractory or relapsed PCNSL have a poor prognosis, with a median survival of 2 
months without additional treatment (Grommes, 2017). The optimal salvage regimen for patients 
with recurrent or refractory PCNSL, especially those relapsing after prior HDCT, has not been 
established. No randomized trials have been conducted so far in this patient population. 
For patients refractory to initial therapy or relapsing few treatment options are available, 
especially for patients failing HDCT and ASCT. While HDCT and ASCT plus consolidating 
WBRT may be an option in selected patients (Kasenda, 2017), most patients only have palliative 
options. Few agents have been investigated prospectively in patients with relapsed or refractory 
PCNSL. Prospective trials using single agents such as pemetrexed, topotecan, and 
temozolomide, as well as rituximab have demonstrated ORRs of 31% to 55% with limited 
median PFS of 1.6 to 5.7 months (Grommes, 2017).Unfortunately, none of these showed 
convincing activity sufficient to be established as standard therapy, and choice of salvage 
treatments depends on the clinical status, toxicities from previous treatments and duration of 
remission. Based on the limited evidence available so far, no treatment standard can be 
recommended (Vitolo, 2016). 


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1.2. 
Compound Background 
1.2.1. 
CD19 as a Therapeutic Target 
CD19 is a 95-kDa glycoprotein present on B-cells from early development until differentiation 
into plasma cells (Stamenkovic, 1988). It is a member of the immunoglobulin superfamily and a 
component of a B-cell surface signal transduction complex that positively regulates signal 
transduction through the B-cell receptor (Brentjens, 2011; Stamenkovic, 1988). CD19 is an 
attractive therapeutic target because it is expressed by most B-cell malignancies, including B-cell 
NHL (B-NHL; [Davila, 2012]). Importantly, the CD19 antigen is not expressed on hematopoietic 
stem cells or on any normal tissue apart from those of the B-cell lineage. 
1.2.2. 
CD19-Targeted Chimeric Antigen Receptors 
CD19-specific chimeric antigen receptors (CARs) are single chain variable fragments (scFv) 
fused to a transmembrane domain and cytoplasmic signaling domains. Expression of the CD19- 
directed CAR in autologous T cells is achieved by ex vivo transfection using a recombinant 
retroviral or lentiviral vector. The CAR is expressed on the T cell surface and redirects the 
transfected T cells to CD19-expressing lymphoma cells, leading to CD19-specific tumor cell 
recognition, lysis, cytokine secretion, and T cell proliferation (Sadelain, 2013). In clinical 
studies, CD19-targeted CARs have demonstrated encouraging activity in adult and pediatric 
subjects with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL) and B-NHL 
(Davila, 2014; Kochenderfer, 2015; Lee, 2015; Maude, 2014; Porter, 2011; Turtle, 2016; Turtle, 
2016). 
Three CD19-directed CAR T therapies have been approved by the US Food and Drug 
Administration (FDA) and Japan Ministry of Health, Labour and Welfare (MHLW). In addition 
two of them were also approved by the European Medicines Agency (EMA): 
• Tisagenlecleucel, approved for the treatment of patients up to age 25 years with 
B-cell precursor ALL that is refractory or in second or later relapse and for adult 
patients with relapsed or refractory (R/R) large B-cell lymphoma after 2 or more lines 
of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise 
specified (NOS), high-grade B-cell lymphoma, and DLBCL arising from follicular 
lymphoma (Kymriah™ United States Product Insert [USPI], 2018; Kymriah, 
Summary of Product Characteristics [SmPC]). 
• Axicabtagene ciloleucel, approved to treat adult patients with relapsed or refractory 
large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL 
NOS, PMBCL, high grade B-cell lymphoma, and DLBCL arising from follicular 
lymphoma (Yescarta USPI, 2019; Yescarta, SmPC). 
• Lisocabtagene maraleucel, approved for the treatment of adult patients with relapsed 
or refractory large B-cell lymphoma after two or more lines of systemic therapy, 
including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including 
DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary 
mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B (Breyanzi 
USPI, 2021). 


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1.2.3. 
JCAR017 Investigational Drug Product 
The JCAR017 investigational drug product is a novel, CD19-targeted, genetically modified, 
autologous, defined composition, T cell immunotherapy. Lisocabtagene maraleucel has been 
accepted as the generic name for JCAR017. JCAR017 is manufactured from autologous 
peripheral blood mononuclear cells (PBMCs) that are obtained via standard leukapheresis 
collection procedures. The PBMCs undergo sequential positive selection for CD8+ and CD4+ T 
cells where the CD4 and CD8 purified T cell populations derived from the same starting material 
(leukapheresis) are separated, subsequently cryopreserved, transfected with CAR and expanded 
through parallel processing in order to ensure the final product is infused to the subjects in a 
defined cell composition. The CD19-specific CAR consists of an scFv binding domain derived 
from a murine CD19-specific monoclonal antibody (mAb; FMC63) and the 4-1BB and CD3ζ 
signaling domains. The truncated human epidermal growth factor receptor (EGFRt) protein is 
co-expressed with the CD19-specific CAR as a cell surface protein for analytical detection of 
transfected T cells. 
The JCAR017 investigational drug product is provided as 2 individually formulated CD8+CAR+ 
and CD4+CAR+ T cell suspensions in media containing dimethyl sulfoxide (DMSO) that are 
thawed and administered separately by intravenous (IV) infusion. JCAR017 is administered 
intravenously. 
Please refer to the Investigator’s Brochure (IB) for detailed information concerning the available 
pharmacology, toxicology, clinical studies, and adverse event (AE) profile of JCAR017. 
1.2.4. 
Clinical Experience with JCAR017 and Related CAR T Cell Products 
JCAR017 is currently being evaluated in the Juno TRANSCEND NHL 001 (017001) study and a 
related CAR T cell product is being evaluated in the PLAT-02 study. In the PLAT-02 study, a 
first-in-human Phase 1 study of pediatric and young adult subjects with relapsed CD19+ B-cell 
ALL (PLAT-02 study; NCT02028455), a total of 43 subjects with relapsed CD19+ B-cell ALL 
were treated with JCAR017 at dose levels ranging from 5 x 105 to 10 x 106 CAR+ T cells/kg. All 
43 infused subjects received lymphodepleting (LD) chemotherapy prior to T cell infusion 
(cyclophosphamide, n=27; cyclophosphamide and fludarabine, n=14; cyclophosphamide and 
etoposide, n=1; fludarabine, n=1). Thirty-nine of the 43 (91%) subjects received infusions at the 
desired 1:1 CD4:CD8 ratio and their infusions were well tolerated with only 1 related AE > 
Grade 2. A total of 93% (40/43) of the subjects had a documented minimal residual disease 
(MRD)-negative CR within 21 days following CAR T cell therapy. The 12-month event-free 
survival (EFS) is 50.8% (95% confidence interval [CI] 36.6, 69.9) and 12-month OS is 69.5% 
(95% CI 55.8, 86.5) (Gardner, 2017). 
The TRANSCEND study is investigating JCAR017 in adult subjects with r/r B-cell NHL (Juno 
TRANSCEND NHL 001 (017001) study; NCT02631044) (Abramson, 2018). A total of 55 
subjects had received JCAR017 at the time of data cutoff (May 4th, 2017). Preliminary data 
suggest promising antitumor activity of JCAR017 in these heavily pretreated, poor prognosis r/r 
subjects with aggressive NHL (median of 3 prior lines of therapy). The overall response rate 
(ORR) reported was 76% with a CR rate at 3 months of 51% and an acceptable safety profile. No 
dose-limiting toxicity (DLT) was observed at dose level DL2 (JCAR017 infusion of 100 x 106 
viable CAR+ T cells) with a trend toward improved response rate at 3 months in patients treated 
at DL2 when compared to DL1: ORR 64% vs 46% and CR 46% vs 33% (trend maintained at the 


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July 04th data cut. Pharmacokinetic (PK) analyses showed that in vivo expansion of CAR+ T 
cells peaks around day 11 after infusion of JCAR017. This is consistent with the reported safety 
with most important toxicities (cytokine release syndrome [CRS] and neurotoxicity [NT]) 
occurring within the first 14 days after infusion. 
Major safety findings include CRS, NT and hematological disorders, including neutropenia, 
thrombocytopenia and anemia. The most significant toxicities reported have been severe 
cytokine release syndrome (sCRS) and NT. Cytokine release syndrome was observed in 19 
(35%) subjects treated, with only 1 subject developing sCRS (Grade 3-4). Neurotoxicity was 
observed in 12 (18%) subjects, of which 9 subjects (16%) developed severe NT (Grade 3-4). 
Median time to onset of CRS after JCAR017 infusion was 5 days, median time to onset of NT 
was 11 days. The median time to resolution to Grade 1 or better was 5 days for CRS and 7 days 
for NT. No unexpected early or late toxicities were reported. No cerebral edema, fatal CRS or 
NT were observed and symptoms were reversible and manageable with appropriate treatment 
intervention and close monitoring (Abramson, 2018). 
The ability of CAR T cells to cross the blood-brain barrier has been reported (Kochenderfer, 
2017) and has been observed in study 017001 (Abramson, 2018). At the time of data analysis, 
the subjects enrolled and experiencing NT had no evidence of CNS involvement. This supports 
the rationale to further investigate CAR T cell therapy in patients with primary CNS or 
secondary CNS involvement. Two subjects with secondary CNS involvement by DLBCL were 
included in study 017001. Both subjects experienced complete resolution of their CNS disease 
with no neurologic adverse events observed. 
JCAR014, a CAR T cell product that expresses the same CD19-specific CAR as JCAR017 but is 
produced using a different manufacturing process, is currently being evaluated in a first-in- 
human Phase 1/2 trial in adult subjects with relapsed/refractory CD19+ ALL, CLL, and NHL 
(2639 study; NCT01865617). Data are available from 41 subjects with NHL, 39 of whom are 
evaluable for efficacy (Turtle, 2016). Among all 41 subjects with NHL, the rate of sCRS was 
13% (4/32) and the rate of severe neurotoxicity was 25% (8/32). The dose of 2 x 107 CAR+ T 
cells/kg was determined to have unacceptable toxicity with two deaths from sCRS at that dose 
level. Fludarabine and cyclophosphamide LD chemotherapy was associated with a higher 
response rate than non-fludarabine regimens. The ORR and CR rate were 74% and 44%, 
respectively, in 27 subjects treated with the fludarabine-containing regimen versus 50% and 8%, 
respectively, in the 12 subjects treated with non-fludarabine-containing regimens. In the group of 
subjects treated with fludarabine-containing LD chemotherapy and a CAR+ T cell dose of 2 x 
106 CAR+ T cells/kg, the ORR was 80% (16/20) and the CR rate was 50% (10/20). 
Data are also available from 36 adult subjects with B-cell ALL treated with JCAR014 as part of 
the 2639 trial (Turtle, 2016). Twelve of the 36 subjects were post allogeneic hematopoietic stem 
cell transplantation (HSCT). CAR+ T cell doses were 2 x 105, 2 x 106, and 2 x 107 CAR+ T 
cells/kg. Lymphodepleting chemotherapy consisted of cyclophosphamide 60 mg/kg on Day 1 
and fludarabine 25 mg/m2 for 3 to 5 days in 23 subjects. The remainder received non- 
fludarabine-containing LD chemotherapy regimens. Use of fludarabine-containing LD 
chemotherapy was associated with increased expansion and persistence of the CAR+ T cells. 
Thirty-four subjects were evaluable for a response assessment: 34 (100%) achieved a 
morphologic bone CR, with 32 of 34 (94%) achieving a bone marrow CR. In 87 subjects 
evaluated for toxicity, the rates of sCRS and Grade ≥ 3 neurotoxicity were 16% and 31%, 


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respectively. Four subjects (4%) died of complications of CRS and one subject experienced 
irreversible neurotoxicity. See the JCAR017 Investigator’s Brochure for further details. 
1.3. 
Rationale 
1.3.1. 
Study Rationale and Purpose 
The purpose of this Phase 2 study is to evaluate the efficacy and safety of JCAR017 in adult 
subjects with aggressive B-NHL. Multiple recent reports in B-NHL have demonstrated 
encouraging activity of CD19-targeted CAR T cell investigational drug products that are 
unselected for T cell subsets (Kochenderfer, 2015; Schuster, 2016). JCAR017 differs from these 
products in that it consists of CD4+ and CD8+ CD19-targeted CAR+ T cells administered in a 
defined composition. It is known that CD4+ T cells enhance CD8+ effector T cell persistence, 
memory formation, and trafficking to antigen-rich tissues. Activated CD8+ T cells have also 
shown poor survival when CD4+ T cell help is absent, and CD4+ T cell help is required during 
recall expansion of memory CD8+ T cells (Bos, 2010; Toes, 1999). Likewise, CAR+ CD4+ T 
cells enhance CAR+ CD8+ cytolytic effector T cell function both in vitro and in vivo 
(Adusumilli, 2014). Thus, since JCAR017 has a defined ratio of CD4+ to CD8+ CD19-targeted 
CAR+ T cells, persistence, trafficking to the tumor, and antitumor activity may be improved 
compared with CAR T cell investigational drug products without a defined composition. 
Emerging data indicates that in vivo expansion of CD19-targeted CAR T cells strongly correlates 
with antitumor response (Gardner, 2017; Kochenderfer, 2015; Schuster, 2016). The antitumor 
activity of CAR T cells in NHL has been lower than that observed in ALL subjects. The effect of 
the tumor microenvironment or bone marrow lymphoma involvement (ie, more accessible target 
antigen) on CAR T cell expansion and function may be important for antitumor activity in NHL. 
Biopsies will be required during this study to assess disease attributes that may affect expansion 
and activity of JCAR017. 
The dose level to be used in this study was evaluated in the Juno TRANSCEND NHL 001 
(017001) study (NCT02631044) being conducted in the US. Preliminary safety, PK and efficacy 
analyses of JCAR017 at dose level DL2 (100 x 106 viable CAR+ T cells) show a well-defined 
safety profile with low incidence of severe CRS or neurotoxicity and a favourable risk/benefit 
ratio. All these supporting the justification for the planned dose to be administered in the 
JCAR017-BCM-001 study (Abramson, 2018). 
1.3.2. 
Lymphodepleting Chemotherapy Rationale 
Data have been published for approximately 40 subjects with NHL who were treated with 3 
different CD19-targeted CAR T cell products; however, there is no consensus on the optimal LD 
chemotherapy regimen to use prior to CD19-targeted CAR T cell therapy. 
Encouraging antitumor activity has been observed in 11 subjects with NHL who received LD 
chemotherapy with a combination of high doses of cyclophosphamide (60 to 120 mg/kg) and 
fludarabine (25 mg/m2/day x 5 days) (Kochenderfer, 2015). However, significant cardiac 
toxicity, neurotoxicity, and death were reported at the highest CAR T cell dose level (5 x 106 
CAR+ T cells/kg). When the CAR T cell dose was reduced to 1 x 106 CAR+ T cells/kg and a 
lower dose regimen of cyclophosphamide (300 mg/m2/day x 3 days) and fludarabine (30 
mg/m2/day x 3 days) was used, the severe cardiac and neurotoxicity was eliminated, and 


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although transient neurotoxicity (aphasia and ataxia) was still evident, encouraging antitumor 
activity was observed (Kochenderfer, 2014). 
Data suggest that CAR T cell expansion, persistence, and antitumor activity are not as 
encouraging and retreatment is not as effective in JCAR014-treated subjects who were 
lymphodepleted with regimens other than fludarabine and cyclophosphamide (Turtle, 2016). 
When a high-dose cyclophosphamide (60 mg/kg) and fludarabine (25 mg/m2/day x 3 to 5 days) 
lymphodepletion regimen was used, preliminary data suggest that cell expansion and antitumor 
activity of JCAR014 are improved; however, similar to the data presented by Kochenderfer et 
al., cardiac toxicity, neurotoxicity, and death were observed with high cell doses (20 x 106 CAR+ 
T cells/kg; see the JCAR017 IB for further details). Cellular expansion was also observed in a 
small number of subjects after retreatment with JCAR014 after fludarabine and 
cyclophosphamide LD chemotherapy, whereas no appreciable expansion was observed in 
subjects retreated with JCAR014 after LD chemotherapy with regimens other than fludarabine 
and cyclophosphamide (Turtle, personal communication). 
The LD chemotherapy regimen employed in the current protocol is similar in intensity to the 
low-dose LD regimens described above. This regimen was selected to limit toxicity and retain 
antitumor activity, as well as to optimize cellular expansion and antitumor activity after 
retreatment and with multiple-dose schedules of JCAR017 infusion. Cyclophosphamide and 
fludarabine given in combination are now being uniformly used as lymphodepletion regimen in 
CAR T cell programs and are also used as standard combination regimen on Celgene’s CAR T 
development programs. Cyclophosphamide and fludarabine will be administered at the same 
dose as in TRANSCEND NHL 001 (017001) study. 
1.3.3. 
Rationale for JCAR017 Dose Selection 
Promising results have been reported for different CD19-directed CARs in the treatment of adult 
(Kochenderfer, 2016; Schuster, 2016; Turtle, 2016) and pediatric (Park, 2016) CD19-positive 
lymphatic malignancies. 
The Juno Phase 1 trial (TRANSCEND NHL 001 (017001), NCT02631044) is evaluating 
JCAR017 at several dose levels after LD chemotherapy with cyclophosphamide (300 mg/m2/day 
x 3 days) combined with fludarabine (30 mg/m2/day x 3 days). The initial dose level selected 
(DL1: 50 x 106 CAR+ T cells) was found to be tolerable, the dose was escalated to 100 x 106 
CAR+ T cells (DL2) and additional dosing schedules were evaluated (Abramson, 2018). 
Preliminary analysis of safety and efficacy of 18 subjects treated at DL2 showed good 
tolerability and efficacy with a single JCAR017 infusion. Based on this data, a dose of 100 x 106 
CAR+ T cells (DL2) was selected for this Phase 2 trial. 
1.3.4. 
Rationale for Pharmacodynamics and Potential Predictive Biomarkers 
The magnitude of CAR T cell expansion and persistence is, in some cases, a predictive 
biomarker that may correlate with response. Upon infusion, CAR T cells can expand > 1000-fold 
followed by a contraction phase and a persistence phase (Davila, 2014; Kalos, 2011). The second 
generation of CAR T cells containing a co-stimulatory domain, CD28 or 4-1BB (CD137) with 
enhanced proliferative capacity and persistence over the first generation of CAR T cells, showed 
marked antitumor effects in B-cell malignancies (Grupp, 2013; Kalos, 2011; Kochenderfer, 
2010; Porter, 2011). Additionally, the administration of high-dose steroids ablated CAR T cell 


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expansion and was associated with recurrence of disease after initially achieving a complete 
response after CAR T cell infusion (Davila, 2014). These findings suggest that monitoring CAR 
T cells in a quantitative, sensitive and relevant manner is advantageous and thus both molecular 
and cellular methods will be used. A threshold for expansion or persistence that determines 
response or response duration remains to be identified. 
An additional factor with the potential to limit CAR T cell persistence is the development of 
immunogenicity. The antigen receptor expressed on CAR T cells is comprised of a chimeric 
protein bearing regions of CD28, CD3, and the scFv derived from a mouse sequence against 
human CD19. The mouse derived sequence and the junctional regions could give rise to unique 
epitopes eliciting an immune response to inhibit CAR T cell persistence leading to CAR T cell 
loss and relapse. Humoral and/or cellular responses to CAR T cells have been reported 
(Kershaw, 2006; Lamers, 2011; Till, 2008) where limited CAR T cell persistence coincided with 
the detection of humoral and anti-CAR T cell immune responses (Lamers, 2011). 
As the development of an immune response to CAR T cells could diminish efficacy, 
immunogenicity will be monitored during the course of the trial for correlation with loss of CAR 
T cell persistence and clinical outcome. 
Severe cytokine release syndrome and neurotoxicity are toxicities observed with CAR T cell 
therapy. Increases in several cytokines such as interleukin (IL)-6, IL-5, IL-10, and interferon 
gamma (IFN-γ) have been observed although the pattern of elevated cytokines varies among 
subjects (Davila, 2014). Some degree of correlation may exist between the development of CRS 
and efficacy. While the severity of CRS has not been shown to be predictive of response, it has 
been associated with disease burden (Maude, 2014). Preliminary observations show a correlation 
of a subset of the aforementioned cytokines as well as additional cytokines such as IL-8, IL-15 
and transforming growth factor alpha (TGF-α) may predict the severity of CRS and 
neurotoxicity. In addition, clinical markers of inflammation, C-reactive protein (CRP) and 
ferritin, are at elevated levels in subjects displaying CRS (Bonifant, 2016; Davila, 2014; Turtle, 
2016). To understand the pathophysiology of potential CAR T cell mediated toxicity, an 
extensive soluble factor panel will be conducted on a multiplex assay platform. 
Based on clinical data available from ALL studies, CD19 antigen loss has been associated with 
relapse in subjects treated with CD19-targeted CAR T cells. Initial estimates indicate 10% to 
20% CD19 epitope loss in pediatric B-ALL while no CD19 antigen loss has been reported in 
adults with CLL after CAR T cell treatment suggesting subject population and/or disease 
indication may contribute to these differences (Grupp, 2013). The molecular characterization of 
CD19 antigen loss in B-ALL indicate a combination of aberrations at the deoxyribonucleic acid 
(DNA) and ribonucleic acid (RNA) level (Ruella, 2016; Sotillo, 2015). While reports of CD19 
antigen expression are preliminary in NHL patients, correlation between CD19 antigen loss and 
relapse have been noted. The expression of CD19 in tumor will be monitored by IHC for 
potential loss of antigen and correlated with relapse. 
The prolonged persistence of CAR T cells and its relevance in efficacy may stem from the 
generation of memory CAR T cells. Based on multi-parameter flow cytometry to characterize the 
expression and phenotype of CD19 CAR T cells directly obtained from treated subjects, both 
CD4+ and CD8+ CAR T cell subsets displayed features associated with the central memory 
phenotype. Expression of CCR7 and higher levels of CD27, CD28 and CD127 were detected on 
the CAR T cells several months post infusion suggesting that persistence and perhaps clinical 


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response may be attributed to this T cell subtype (Kalos, 2011). However, the lack of persistence 
alone may not completely address CAR T cell treatment failure. A marker associated with T cell 
dysfunction, programmed cell death protein 1 (PD-1), was observed at high levels approximately 
one month post infusion and readily detected albeit at lower levels at five months. Therefore, a 
phenotypic analysis of the CAR T cells for various markers of exhaustion to understand features 
associated with persistence and function will be conducted. In addition, immune cells with 
suppressive activity such as T regulatory cells that may modulate CAR T cell function will be 
evaluated. 
Exploratory assessments using tumor tissue, such as IHC, gene expression profiling, or whole 
exome sequencing will be correlated with disease features and JCAR017 efficacy. Additional 
correlative analyses will be conducted to understand features of JCAR017 PK, and 
characteristics of JCAR017 cells and circulating immune cells on JCAR017 persistence and 
function, clinical response, duration of response and toxicity. 


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2. 
STUDY OBJECTIVES AND ENDPOINTS 
Table 1: 
Study Objectives 
 
Primary Objectives 
The primary objectives are: 
Cohorts 1, 2, 3, 4, and 5 
• To determine the efficacy, defined as overall response rate (ORR) of JCAR017 in 
subjects with aggressive B-cell non-Hodgkin lymphoma 
Cohort 7 
• To evaluate the safety of JCAR017 treatment in subjects intended to be treated as 
outpatients 
Secondary Objectives 
The secondary objectives are: 
• To evaluate the safety and feasibility of administering JCAR017 (Cohorts 1, 2, 3, 4, 
and 5) 
• To determine the efficacy, defined as ORR of JCAR017 in subjects intended to be 
treated as outpatients (Cohort 7) 
• To evaluate other measures of efficacy of JCAR017 (eg, complete response rate 
[CRR], event-free survival [EFS], progression-free survival [PFS], overall survival 
[OS], duration of response [DOR]) 
• To characterize the pharmacokinetic (PK) profile of JCAR017 in the peripheral blood 
measured using qPCR detection for the JCAR017 vector sequence 
• To describe changes in health-related quality of life (HRQoL) using the global 
health/QoL, fatigue, physical and cognitive functioning subscales of the European 
Organisation for Research and Treatment of Cancer – Quality of Life C30 
questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer 
Therapy-Lymphoma “Additional concerns” subscale (FACT-LymS) 


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Table 1: 
Study Objectives (Continued) 
 
Exploratory Objectives 
The exploratory objectives are: 
• To characterize the PK profile of JCAR017 in the peripheral blood using flow 
cytometry 
• To evaluate pharmacodynamic markers of JCAR017, including soluble factors such 
as chemokines and cytokines 
• To evaluate clinical outcomes versus histologies, disease characteristics and subject 
characteristics 
• To evaluate the tumor and tumor microenvironment for mechanisms of response and 
resistance to JCAR017 
• To describe the effect of treatments directed at severe cytokine release syndrome 
(sCRS) and neurotoxicity on duration and severity of these events 
• To describe JCAR017 PK and pharmacodynamic effects on JCAR017 cell persistence 
and on the response of JCAR017 treatment of the disease under study 
• To characterize the prevalence and incidence of humoral immune responses to 
JCAR017 
• To characterize the subject experience on JCAR017 using patient interviews 
• To measure hospital resource utilization, including hospitalization rate 
• To describe changes in the other domains of HRQoL using the rest of subscales in 
EORTC QLQ-C30 questionnaire (ie, those not specified in the secondary objectives) 
• To describe changes in health utility scores and global health using the European 
Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L) 


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Table 2: 
Study Endpoints 
 
Endpoint 
Name 
Description 
Timeframe 
Primary 
Non-Hodgkin lymphoma 
(NHL; including 
secondary central nervous 
system [CNS] 
involvement): Overall 
Response Rate (ORR) 
Cohorts 1, 2, 3, and 4 
Proportion of subjects achieving a 
complete response (CR) or partial 
response (PR) based on the 
Lugano classification (Cheson, 
2014) (see Appendix C) 
Up to 2 years after 
JCAR017 infusion 
Relapsed/refractory (r/r) 
primary central nervous 
system lymphoma 
(PCNSL): ORR 
Cohort 5 
Proportion of subjects achieving a 
complete response (CR)/complete 
response unconfirmed (CRu) or 
PR based on the International 
Workshop to Standardize 
Baseline Evaluation and 
Response Criteria in Primary 
CNS Lymphoma (Abrey, 2005) 
Up to 2 years after 
JCAR017 infusion 
Safety in subjects intended 
to be treated as outpatients 
Cohort 7 
Type, frequency, and severity of 
all adverse events (AEs), 
including serious adverse events 
(SAEs) and laboratory 
abnormalities 
Up to 2 years after 
JCAR017 infusion 
Secondary 
Safety 
Type, frequency, and severity of 
AEs, including SAEs and 
laboratory abnormalities 
Up to 2 years after 
JCAR017 infusion 
Safety in subjects treated 
as outpatients 
Type, frequency, and severity of 
AEs, including SAEs and 
laboratory abnormalities 
Up to 2 years after 
JCAR017 infusion 
ORR in subjects intended 
to be treated as outpatients 
Cohort 7 
Proportion of subjects achieving a 
CR or PR based on the Lugano 
classification (Cheson, 2014) (see 
Appendix C) 
Up to 2 years after 
JCAR017 infusion 
Complete response rate 
(CRR) 
Proportion of subjects achieving a 
CR (or CR and CRu for subjects 
with PCNSL) following 
JCAR017 infusion 
Up to 2 years after 
JCAR017 infusion 
Event-free survival (EFS) 
Time from JCAR017 infusion to 
death from any cause, progressive 
disease (PD), or starting a new 
anticancer therapy, whichever 
occurs first 
Up to 2 years after 
JCAR017 infusion 


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Endpoint 
Name 
Description 
Timeframe 
Secondary 
Progression-free survival 
(PFS) 
Time from JCAR017 infusion to 
the first documentation of PD, or 
death due to any cause, whichever 
occurs first 
Up to 2 years after 
JCAR017 infusion 
Overall survival (OS) 
Time from JCAR017 infusion to 
time of death due to any cause 
Up to last subject last 
visit 
Duration of response 
(DOR) 
Time from first response to 
progressive disease or death 
from any cause, whichever 
occurs first 
Up to 2 years after 
JCAR017 infusion 
Pharmacokinetics (PK) by 
qPCR 
Maximum concentration (Cmax), 
time to peak concentration (Tmax), 
area under the curve (AUC), and 
persistence of JCAR017 in 
peripheral blood as assessed by 
qPCR 
Up to 2 years after 
JCAR017 infusion 
Health Related Quality of 
Life (domain of interest) 
HRQoL using the global 
health/QoL, fatigue, physical and 
cognitive functioning subscales of 
the European Organisation for 
Research and Treatment of 
Cancer – Quality of Life C30 
questionnaire (EORTC QLQ- 
C30) and the Functional 
Assessment of Cancer Therapy- 
Lymphoma “Additional 
concerns” subscale (FACT- 
LymS) 
Up to 2 years after 
JCAR017 infusion 
Exploratory 
Blood biomarker 
Analyses of soluble factors, 
including, but not limited to, 
cytokines and chemokines, 
immune cell subsets and gene 
expression analyses 
Up to 6 months after 
JCAR017 infusion 
Immunogenicity 
assessments 
Humoral immune response (anti- 
therapeutic antibody [ATA]). Cell 
mediated immune response may 
also be assessed 
Up to 2 years after 
JCAR017 infusion 
Tumor biomarker 
Cellular and molecular profiling 
of tumor tissue to explore 
potential efficacy and resistance 
mechanisms 
Up to 2 years after 
JCAR017 infusion 


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Endpoint 
Name 
Description 
Timeframe 
Exploratory 
PK by flow cytometry 
Maximum concentration (Cmax), 
time to peak concentration (Tmax), 
area under the curve (AUC), and 
persistence of JCAR017 in 
peripheral blood as assessed by 
flow cytometry 
Up to 2 years after 
JCAR017 infusion 
Safety 
Response and time to resolution 
for severe cytokine release 
syndrome (sCRS) and/or 
neurotoxicity to interventions 
Up to 2 years after 
JCAR017 infusion 
Hospital resource 
utilization 
Number of inpatient intensive 
care unit (ICU) days, and 
outpatient visits 
Up to 2 years after 
JCAR017 infusion 
HRQoL (other) 
Other domains of HRQoL (not 
specified as secondary endpoints) 
measured by the rest of subscales 
of EORTC QLQ-C30 
Up to 2 years after 
JCAR017 infusion 
Health Utility 
Health utility scores and overall 
health as measured by EQ-5D-5L 
Up to 2 years after 
JCAR017 infusion 
Subject experience on 
JCAR017 
Qualitative data obtained from 
completion of patient interviews 
Up to 2 years after 
JCAR017 infusion 


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3. 
OVERALL STUDY DESIGN 
3.1. 
Study Design 
This study is a single-arm, multi-cohort, multi-center, Phase 2 study to determine the efficacy 
and safety of JCAR017 in adult subjects with aggressive B-NHL. 
Subjects will be enrolled into one of 6 cohorts as listed below (see Figure 1). 
• Cohort 1: Subjects with DLBCL not otherwise specified (NOS; de novo or 
transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and 
BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBL) and follicular 
lymphoma Grade 3B (FL3B) per World Health Organization (WHO) 2016 
classification (Swerdlow, 2016), after ≥ 2 lines of therapy*, including an 
anthracycline and rituximab (or other CD20-targeted agent) 
• Cohort 2: Transplant not eligible (TNE) subjects with DLBCL NOS (de novo or 
tFL), HGBL and FL3B per WHO 2016 classification (Swerdlow, 2016), who failed 
first line therapy*, including an anthracycline and rituximab (or other CD20-targeted 
agent) 
− Transplant not eligible subjects will include those who are deemed ineligible for 
high-dose chemotherapy and HSCT due to age, performance status or 
comorbidity, while also having adequate organ function for CAR T cell treatment. 
At the very least, subjects have to meet one of the following criteria: 
a) Age ≥ 70 years 
b) ECOG performance status ≥ 2 
c) Impaired pulmonary function (diffusion capacity of carbon monoxide [DLCO] 
≤ 60%, adjusted for hemoglobin concentration using the Dinakara equation 
d) Impaired cardiac function (left ventricular ejection fraction [LVEF] < 50%) 
e) Impaired renal function (creatinine clearance [CrCl] < 60 mL/min) 
f) Impaired hepatic function (aspartate aminotransferase [AST] / alanine 
aminotransferase[ALT] > 2 x upper limit of normal [ULN], bilirubin ≥ 2 
mg/dL or cirrhosis Child-Pugh B or C) 
− Comorbidity will be assessed using Appendix G (HCT)-specific comorbidity 
index (HCT-CI) score (Sorror, 2005) to better describe the population in the 
analysis 
• Cohort 3 (Japan only): Subjects meeting eligibility criteria for either Cohort 1 or 2 
• Cohort 4: Subjects with newly diagnosed HGBL. Subjects must be eligible for 
anthracycline and rituximab (or other CD20-targeted agent) containing regimen as 
induction prior to consolidation with JCAR017** 
• Cohort 5: Subjects with primary central nervous system lymphoma (PCNSL), who 
failed first line therapy with HDCT and ASCT, or who failed to proceed to HDCT 
and ASCT due to failure of PBSC mobilization or insufficient response at the 


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completion of induction therapy with high-dose methotrexate-based 
polychemotherapy regimen (eg high dose methotrexate, high dose cytarabine, 
rituximab and thiotepa [MATRix regimen]) 
• Cohort 6: (REMOVED) 
• Cohort 7: Subjects meeting eligibility criteria for Cohort 1 and suitable for outpatient 
treatment*** 
* For subjects with transformed disease, the subject should have had at least 2 lines of 
systemic therapy for his/her transformed disease (ie, DLBCL) for Cohort 1 and 1 line for 
Cohort 2 to be eligible. Lines of therapy do not include those given for a previously indolent 
condition (ie, follicular lymphoma). Subjects do NOT have to have anthracycline for their 
DLBCL if received for indolent disease. 
** For subjects already undergoing anthracycline and rituximab containing regimen, 
eligibility is to be discussed with Medical Monitor. Subjects with complete metabolic 
response after 2 cycles of induction will proceed with JCAR017 infusion only at time of 
relapse, if applicable. 
*** Subjects must meet the conditions for outpatient treatment and monitoring as outlined in 
the Outpatient Administration and Monitoring Guidance for Lisocabtagene Maraleucel. 
Note: Subjects with secondary CNS lymphoma involvement may enroll in Cohorts 1 to 4 and 
7; subjects with PCNSL are eligible for Cohort 5. Subject selection must consider clinical 
risk factors for severe adverse events (AEs) and alternative treatment options. Subjects 
should only be enrolled if the Investigator considers the potential benefit outweighs the risk 
for the subject. For Cohort 5 and to not compromise safety, subject selection has been 
restricted to those fit enough to be considered for HDCT and ASCT as their prior therapy. 
The first 3 subjects in Europe in Cohort 1 will be treated with a minimum interval of 14 days 
between JCAR017 infusions and assessed for acute safety 28 days after the third subject has 
received JCAR017 infusion. In addition, the product characteristics of the JCAR017 cell product 
manufactured with processing steps in Europe will be evaluated. If criteria for safety and 
feasibility are met, Cohort 1 will continue enrollment without gating and additional Cohorts 2, 4, 
5 and 7 may be opened at Celgene’s discretion. A minimum of 14 days treatment interval will 
also apply to all subjects treated in Cohort 5. 
The first 10 subjects treated with JCAR017 in Europe must be hospitalized for a minimum of 14 
days after JCAR017 infusion, unless otherwise recommended by a local authority. Experience to 
date with JCAR017 from the Juno TRANSCEND NHL 001 (017001) study suggests that 
outpatient administration of JCAR017 can be provided safely without compromising the 
subject’s safety when appropriate education is provided and hospital admission is done upon 
symptoms of toxicity. Outpatient infusion of JCAR017 was associated with a 68% decrease in 
hospital length of stay (Palomba, 2018). Selected countries/sites will participate in the dedicated 
outpatient cohort. In order to enroll subjects in Cohort 7, sites must have treated at least 3 
DLBCL subjects with CD19-targeted CAR T cell therapy, and must have a suitable 
infrastructure to allow for outpatient treatment and monitoring as outlined in the Outpatient 
Administration and Monitoring Guidance for Lisocabtagene Maraleucel. 


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Safety data will be reviewed on an ongoing basis. An early safety assessment will be performed 
28 days after JCAR017 is administered to the 10th subject treated in Europe. Enrollment will be 
halted if the observed mortality rate is > 30%, irrespective of causality, or if > 50% of subjects 
who undergo leukapheresis fail to have a satisfactory cell product available for infusion. 
In addition, an early safety assessment will be performed 28 days after JCAR017 is administered 
to the 10th subject treated in Cohort 2. Enrollment into Cohort 2 will be halted if the observed 
mortality rate within 28 days post infusion is > 30% (excluding death related to disease 
progression or relapse). 
The first 3 subjects in Japan will be treated with a minimum interval of 14 days between 
JCAR017 infusions and assessed for acute safety 28 days after the third subject has received 
JCAR017 infusion. In addition, the first 10 subjects treated with JCAR017 in Japan will be 
hospitalized for a minimum of 14 days after JCAR017 infusion. The acute and subacute toxicity 
profile of JCAR017 cell product manufactured entirely at the current manufacturing site in the 
US has already been established in subjects with r/r B-NHL with good tolerability observed in 
subjects with DLBCL (Abramson, 2018). 
In addition, a staggered dosing approach will also be utilized for all new sites (Europe and Japan) 
without prior experience of administering CAR T cell therapies as follows: 
• 1st subject infusion, wait 14 days 
• 2nd subject infusion, wait 14 days 
Following completion of this site-staggered enrollment approach, the site may proceed with 
subject enrollment as communicated by Celgene. Calls will be scheduled at least monthly with 
all sites and their respective Investigators aiming to review and share all safety related events. 
Prior to initiation of any study procedure (screening period), subjects must provide informed 
consent. Once enrolled and during the pretreatment period (see Figure 2), subjects will undergo 
leukapheresis to enable JCAR017 cell product generation. Upon successful JCAR017 cell 
product generation, subjects will enter the treatment period and receive LD chemotherapy 
followed by infusion of JCAR017, 2 to 7 days after completion of LD chemotherapy. JCAR017 
will be administered at a dose of 100 x 106 JCAR017-positive transfected viable T cells (CAR+ 
T cells). 
After treatment with JCAR017, subjects will enter the post-treatment period. A first response 
assessment will be performed 28 days after JCAR017 infusion. Subjects will be followed for 2 
years after their JCAR017 infusion for safety, disease status, survival and health-related quality 
of life and utility values measured using European Organisation for Research and Treatment of 
Cancer – Quality of Life C30 questionnaire (EORTC QLQ-C30) and the European Quality of 
Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L) and the Functional Assessment 
of Cancer Therapy-Lymphoma “Additional concerns” subscale (FACT-LymS). 
In addition, when feasible, all subjects will be invited to participate in interviews during their 
participation in the study to document their experience with JCAR017. 
Delayed adverse events following exposure to gene-modified T cells will be assessed and long- 
term persistence of these modified T cells, including vector integration sites as well as the 
generation of replication competent retrovirus will continue to be monitored under a separate 


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Long-term follow-up (LTFU) protocol for up to 15 years after JCAR017 infusion as per 
competent authority guidelines. 
The decision to discontinue a subject from the study is the responsibility of the Investigator or 
designee. Celgene will not delay or refuse this decision. However, prior to discontinuing a 
subject, the Investigator should contact the Medical Monitor and forward appropriate supporting 
documents for review and discussion. 
The study will be conducted in compliance with the International Council for Harmonisation 
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good 
Clinical Practice (GCP) and applicable regulatory requirements. 
3.2. 
Stopping Rules 
Adverse events and serious adverse events (SAEs) are expected to occur frequently in this study 
based on the subject population being accrued and on the nature of the advanced hematologic 
malignancy under study. Regular systematic review of SAEs will serve as the basis for pausing 
or prematurely stopping the study. Unexpected SAEs that are related to JCAR017 will be the 
primary criteria for pausing or stopping the study for all study cohorts except Cohort 7. Review 
of these SAEs, and any decision to pause enrollment or terminate the study, will be determined 
by the Data Safety Monitoring Board (DSMB) and Celgene. Decisions to pause enrollment or 
terminate a given cohort or the study will be communicated promptly to Investigators, to the 
Institutional Review Boards (IRBs)/Ethics Committees (ECs), Institutional Biosafety 
Committees (IBCs) (if applicable), and to the appropriate regulatory authorities. 
3.2.1. 
Criteria for Pausing or Stopping the Study 
A study cohort may be suspended or terminated for the following reasons: 
• Any subject develops uncontrolled JCAR017 proliferation that is unresponsive to 
treatment 
• Any subject develops detectable replication-competent lentivirus during the study 
• Celgene, IRB/EC, or DSMB decides that subject safety may be compromised by 
continuing the study 
• Celgene decides to discontinue/limit the development of JCAR017 in the indications 
under evaluation 
3.2.2. 
Criteria for Pausing or Stopping Cohort 7 
Safety monitoring boundaries based on Bayesian framework (Thall, 1994) have been included to 
help detect signals that may occur in Cohort 7. Safety monitoring boundaries are reported on 
Table 3. If the safety boundaries are crossed, Cohort 7 enrollment will be paused and ad hoc 
DSMB meetings will be held to review the data. Cohort 7 will remain paused for enrollment 
pending the DSMB recommendations. 
Events occurring within 30 days of a JCAR017 cell product infusion defined for the safety 
boundaries are as follows: 
• A Grade 3 or above, JCAR017-related, treatment-emergent neurological toxicity 


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• Prolonged Grade 4 and Grade 5 individual safety events 
− Life-threatening (Grade 4) toxicity attributable to JCAR017 that is unexpected, 
unmanageable (ie, does not resolve to Grade 3 or lower within 7 days), and 
unrelated to chemotherapy 
− Death related to JCAR017 therapy 
Table 3: 
Safety Monitoring Boundaries for Cohort 7 Based on Thall and Simon 
(Thall, 1994) 
 
Number of Subjects Treated in Cohort 7 
Incidence 
1-5 
No Stopping 
6-7 
≥ 5 
8-9 
≥ 6 
10-11 
≥ 7 
12-13 
≥ 8 
14-15 
≥ 9 
16-17 
≥ 10 
18-19 
≥ 11 
20-21 
≥ 12 
22-23 
≥ 13 
24-26 
≥ 14 
Note: No stopping boundaries for less than 6 subjects in Cohort 7. The enrollment will be paused if the boundaries 
are crossed, eg, out of 10 subjects treated in Cohort 7, at least 7 subjects experience specified toxicity events. 
 
3.3. 
Study Duration for Subjects 
This study will enroll over approximately 40 months and will consist of 3 periods: 
• The pretreatment period will consist of screening for eligibility, leukapheresis and a 
pretreatment evaluation (prior to LD chemotherapy) 
• The treatment period will start with LD chemotherapy, followed by JCAR017 
infusion 2 to 7 days after completion of LD chemotherapy. A first response 
evaluation will be performed at approximately 28 days after JCAR017 infusion. 
• The post-treatment period will consist of further efficacy and safety follow-up visits 
at approximately 2, 3, (at 4 months for Cohort 5), 6, 9, 12, 18 and 24 months after 
JCAR017 infusion 
3.4. 
End of Trial 
The End of Trial is defined as either the date of the last visit of the last subject completing the 
post-treatment follow-up of this study or the date when the last subject enters the LTFU study, or 
the date of receipt of the last data point from the last subject that is required for primary, 
secondary and/or exploratory analysis, as pre-specified in the protocol, whichever is the later 
date. 


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Figure 1: 
Overall Study Design 
 
Abbreviations: CNS = central nervous system; CR = complete response; DLBCL = diffuse large B-cell lymphoma; DOR = duration of response; ECOG = 
Eastern Cooperative Oncology Group; EFS = event-free survival; FL3B = follicular lymphoma Grade 3B; HGBL = High-grade B-cell lymphoma with MYC and 
BCL2 and/or BCL6 rearrangements with DLBCL histology; HSCT = hematopoietic stem cell transplantation; L = line(s) of therapy; max= maximum; MRI = 
magnetic resonance imaging; NHL = non-Hodgkin lymphoma; NOS = not otherwise specified; ORR = overall response rate; OS = overall survival; PCNSL = 
primary central nervous system lymphoma; PET = positron emission tomography; PFS = progression-free survival; tFL = transformed follicular lymphoma; TNE 
= transplant not eligible. 


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Figure 2: 
Study Schematic 
 
 
Abbreviations: Flu/Cy = fludarabine/cyclophosphamide; IV = intravenous. 


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4. 
STUDY POPULATION 
4.1. 
Number of Subjects 
This study will enroll approximately 116 adult subjects in Europe and Japan. 
4.2. 
Inclusion Criteria 
Subjects must satisfy the following criteria to be enrolled in the study: 
1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF) 
2. Subject must understand and voluntarily sign an ICF prior to any study-related 
assessments/procedures being conducted 
3. Subject is willing and able to adhere to the study visit schedule and other protocol 
requirements 
4. Investigator considers the subject is appropriate for adoptive T cell therapy 
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Subjects not 
eligible for transplant (TNE) in Cohorts 2 and 3 and subjects in Cohort 5 may be enrolled 
with ECOG of 2 only if they meet all other inclusion/exclusion criteria. 
6. Subjects with one of the following: 
• Cohort 1: Subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 
2016 classification (Swerdlow, 2016), after ≥ 2 lines of therapy*, including an 
anthracycline and rituximab (or other CD20-targeted agent) 
• Cohort 2: Transplant not eligible subjects with DLBCL NOS (de novo or tFL), HGBL 
and FL3B per WHO 2016 classification (Swerdlow, 2016), who failed first line 
therapy*, including an anthracycline and rituximab (or other CD20-targeted agent) 
− Transplant not eligible subjects will include those who are deemed ineligible for 
high-dose chemotherapy and HSCT due to age, performance status or 
comorbidity, while also having adequate organ function for CAR T cell treatment. 
At the very least, subjects have to meet one of the following criteria: 
a) Age ≥ 70 years 
b) ECOG performance status ≥ 2 
c) Impaired pulmonary function (DLCO ≤ 60%, adjusted for hemoglobin 
concentration using the Dinakara equation) 
d) Impaired cardiac function (LVEF < 50%) 
e) Impaired renal function (CrCl < 60 mL/min) 
f) Impaired hepatic function (AST/ALT > 2 x ULN, bilirubin ≥ 2 mg/dL or 
cirrhosis Child-Pugh B or C) 
− Subjects must fulfill all other inclusion and exclusion criteria 


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• Cohort 3 (Japan only): Subjects meeting eligibility criteria for either Cohort 1 or 2 
• Cohort 4: Subjects with newly diagnosed HGBL. Subjects must be eligible for 
anthracycline and rituximab (or other CD20-targeted agent) containing regimen as 
induction prior to consolidation with JCAR017** 
• Cohort 5: Subjects with PCNSL who failed first line therapy with HDCT and ASCT, 
or who failed to proceed to HDCT and ASCT due to failure of PBSC 
mobilization or insufficient response at the completion of induction therapy with 
high-dose methotrexate-based polychemotherapy regimen (eg, high dose 
methotrexate, high dose cytarabine, rituximab and thiotepa [MATRix regimen]) 
• Cohort 6: (REMOVED) 
• Cohort 7: Subjects meeting eligibility criteria for Cohort 1 and suitable for outpatient 
treatment*** 
* For subjects with transformed disease, the subject should have had at least 2 lines of 
systemic therapy for his/her transformed disease (ie, DLBCL) for Cohort 1 and 1 line for 
Cohort 2 to be eligible. Lines of therapy do not include those given for a previously 
indolent condition (ie, follicular lymphoma). Subjects do NOT have to have 
anthracycline for their DLBCL if received for indolent disease. 
** For subjects already undergoing anthracycline and rituximab containing regimen, 
eligibility is to be discussed with Medical Monitor. Subjects with complete metabolic 
response after 2 cycles of induction will proceed with JCAR017 infusion only at time of 
relapse, if applicable. 
*** Subjects must meet the conditions for outpatient treatment and monitoring as 
outlined in the Outpatient Administration and Monitoring Guidance for Lisocabtagene 
Maraleucel. 
Note: Subjects with secondary CNS lymphoma involvement may enroll in Cohorts 1 to 4 
and 7; subjects with PCNSL are eligible for Cohort 5. Subject selection must consider 
clinical risk factors for severe adverse events (AEs) and alternative treatment options. 
Subjects should only be enrolled if the Investigator considers the potential benefit 
outweighs the risk for the subject. For Cohort 5 and to not compromise safety, subject 
selection has been restricted to those fit enough to be considered for HDCT and ASCT as 
their prior therapy. 
7. Histological confirmation of diagnosis at last relapse. Enough tumor material must be 
available for central confirmation of diagnosis, otherwise a new tumor biopsy is 
mandated. 
Note: If the subject did not experience CR since last biopsy, the most recent biopsy will 
be considered adequate to participate in the trial. For subjects with PCNSL, at a 
minimum, corresponding pathology report is required if archival tumor material is not 
available and repeated biopsy not feasible. 
8. For subjects with NHL (except Cohort 5): Subjects must have positron emission 
tomography (PET)-positive disease as per Lugano Classification (Cheson, 2014) 


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9. For subjects with PCNSL: Subjects must have disease that is objectively measurable by 
International Workshop to Standardize Baseline Evaluation and Response Criteria in 
Primary Central Nervous System Lymphoma (Abrey, 2005). Cerebrospinal fluid (CSF) 
cytology will be repeated to monitor leptomeningeal disease. 
10. Adequate organ function, defined as: 
• Adequate bone marrow function to receive LD chemotherapy as assessed by the 
Investigator 
• Serum creatinine < 1.5 x ULN or creatinine clearance > 30 mL/min (estimated 
glomerular filtration rate [eGFR] by Cockroft-Gault) 
• Alanine aminotransferase (ALT) ≤ 5 x ULN and total bilirubin < 2.0 mg/dL (or 
< 3.0 mg/dL for subjects with Gilbert’s syndrome or lymphomatous infiltration of the 
liver) 
• Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common 
Terminology Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) 
≥ 92% on room air 
• Adequate cardiac function, defined as LVEF ≥ 40% as assessed by echocardiogram 
or multigated acquisition (MUGA) scan performed within 4 weeks prior to 
leukapheresis 
11. Adequate vascular access for leukapheresis procedure 
12. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage 
in other individuals after the JCAR017 infusion 
13. Female subjects of childbearing potential (FCBP) must: 
a. Have two negative pregnancy tests as verified by the Investigator (one negative serum 
beta human chorionic gonadotropin [ß-hCG] pregnancy test result at screening and 
one negative serum pregnancy test within 48 hours prior to the first dose of LD 
chemotherapy). This applies even if the subject practices true abstinence* from 
heterosexual contact 
b. Either commit to true abstinence* from heterosexual contact (which must be 
reviewed on a monthly basis and source documented) or agree to use, and be able to 
comply with, effective contraception without interruption. Contraception methods 
must include 1 highly effective (barrier) method of contraception from screening until 
at least 12 months following LD chemotherapy 
Note: Highly effective methods are defined as those that result in a low failure rate 
(ie, less than 1% per year) when used consistently and correctly. The following are 
examples of contraception: 
Highly effective methods: 
− Intrauterine device (IUD) 
− Hormonal (birth control pill, injections, implants) 
− Tubal ligation 


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− Partner’s vasectomy 
c. Agree to abstain from breastfeeding during study participation and for at least 12 
months following LD chemotherapy 
d. There is insufficient exposure data to provide any recommendation concerning the 
duration of contraception and the abstaining from breastfeeding following treatment 
with JCAR017. Any decision regarding contraception and breastfeeding after 
JCAR017 infusion should be discussed with the treating physician 
14. Male subjects must: 
a. Practice true abstinence* (which must be reviewed on a monthly basis and source 
documented) or agree to use a condom during sexual contact with a pregnant female 
or a female of childbearing potential while participating in the study and until at least 
12 months following LD chemotherapy even if he has undergone a successful 
vasectomy 
b. There is insufficient exposure data to provide any recommendation concerning the 
duration of contraception following treatment with JCAR017. Any decision regarding 
contraception after JCAR017 infusion should be discussed with the treating 
physician. 
* True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the 
subject. In contrast, periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
4.3. 
Exclusion Criteria 
The presence of any of the following will exclude a subject from enrollment: 
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric 
illness that would prevent the subject from participating in the study 
2. Subject has any condition including the presence of laboratory abnormalities, which 
would place the subject at unacceptable risk if participating in the study 
3. Subject has any condition that confounds the ability to interpret data from the study 
4. Subjects with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary 
cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), 
Epstein-Barr virus (EBV) positive DLBCL of the elderly, Burkitt lymphoma, and 
intraocular lymphoma 
5. Subjects with prior history of malignancies, other than aggressive r/r NHL, unless the 
subject has been in remission for ≥ 2 years with the exception of the following non- 
invasive malignancies: 
• Basal cell carcinoma of the skin 
• Squamous cell carcinoma of the skin 
• Carcinoma in situ of the cervix 
• Carcinoma in situ of the breast 


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• Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, 
nodes, metastasis] clinical staging system) or prostate cancer that is curative 
• Other completely resected stage 1 solid tumor with low risk for recurrence 
6. Treatment with any prior gene therapy product 
7. Subjects who have received previous CD19-targeted therapy 
8. Human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C: 
• Subjects with a history of or active HIV are excluded 
• Subjects with active hepatitis B, or active hepatitis C are excluded 
− Subjects with a negative polymerase chain reaction (PCR) assay for viral load for 
hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen 
and/or anti-hepatitis B core antibody with negative viral load are eligible and 
should be considered for prophylactic antiviral therapy 
9. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including 
tuberculosis) despite appropriate antibiotics or other treatment at the time of 
leukapheresis or JCAR017 infusion 
10. Presence of acute or chronic graft-versus-host disease (GVHD) 
11. Active autoimmune disease requiring immunosuppressive therapy 
12. History of any one of the following cardiovascular conditions within the past 6 months: 
• Heart failure class III or IV as defined by the New York Heart Association (NYHA) 
• Cardiac angioplasty or stenting 
• Myocardial infarction 
• Unstable angina 
• Other clinically significant cardiac disease 
13. History or presence of clinically relevant CNS pathology not related to disease under 
study such as epilepsy, seizure, aphasia, stroke, cerebral edema, severe brain injuries, 
dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis 
14. Pregnant or nursing women 
15. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with 
fludarabine or cladribine within 3 months of leukapheresis 
16. Use of the following (see Section 8.2 for full details): 
• Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or 
equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 
infusion. Physiologic replacement, topical, and inhaled steroids are permitted. 
• Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2) 
given after leukapheresis to maintain disease control must be stopped ≥ 7 days prior 
to LD chemotherapy 


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• Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 
week prior to leukapheresis. Oral anticancer agents, including lenalidomide and 
ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis 
• Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide > 300 mg/m2, 
ifosfamide, bendamustine) within 2 weeks prior to leukapheresis 
• Experimental agents within 4 weeks prior to leukapheresis unless no response or 
progressive disease (PD) is documented on the experimental therapy and at least 3 
half-lives have elapsed prior to leukapheresis 
• Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 
infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, 
mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti- 
tumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R) 
• Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion 
• Radiation within 6 weeks prior to leukapheresis. Subjects must have progressive 
disease in irradiated lesions or have additional non-irradiated, PET-positive lesions to 
be eligible. Radiation to a single lesion, if additional non-irradiated, measurable PET- 
positive lesions are present, is allowed up to 2 weeks prior to leukapheresis. Prior 
WBRT for subjects enrolled in Cohort 5 is not allowed 
• Allogeneic HSCT within 90 days prior to leukapheresis 
• Prior hematopoietic stem cell transplant (only applicable to Cohort 2) 
• Systemic immunostimulatory agents (including but not limited to interferon and IL-2) 
within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to JCAR017 
infusion 
17. Progressive vascular tumor invasion, thrombosis, or embolism 
18. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation 
19. Known severe hypersensitivity to DMSO or Dextran 


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5. 
TABLE OF EVENTS 
Table 4: 
Table of Events 
 
Pretreatment Period 
Treatment Period 
Post-Treatment Period 
Survi 
val 
Fol- 
low- 
up 
Screen- 
ing 
Leuka- 
pheresis 
Pre- 
Treat- 
ment 
Evalua- 
tion 
LD 
Chemo- 
therapy 
JCAR017 
Infusion 
Follow-Up 
Study Day 
Up to 14 
days 
before 
leuka- 
pheresisdd 
Approx- 
imately 
35 days 
before 
Day 1 
Within 7 
days 
before LD 
chemo- 
therapy 
Start 5 
to 10 
days 
before 
Day 1ee 
1 
2 
3 
4 
8 
11 
15 
22 
29 
60 
90/ 
120jj 
180 270 
365 
545 
730 
(EOS) 
or ET 
q3m 
Visit Window (Days) 
- 
- 
- 
- 
- 
- 
- 
+1 
±1 
±1 
±2 
±2 
±2 +14 
+14 +35 +35 +35 
+35 
+35 
±30 
STUDY PROCEDURES 
Informed consent 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Eligibility criteria 
x 
- 
xy 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Medical history 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
ECOG 
x 
x 
x 
x 
x 
- 
- 
- 
x 
- 
x 
x 
x 
x 
xa, jj 
xa 
xa 
xa 
xa 
xa 
- 
HCT-CIx 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Frailty index scorex 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Pulmonary function test 
(DLCO and FEV1)x 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Height 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Weight 
x 
- 
x 
- 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Physical examinationb 
xaa 
- 
xaa 
- 
x 
x 
x 
x 
x 
x 
x 
x 
x 
xa 
xa, jj 
xa 
xa 
x 
- 
x 
- 
Routine neurologic 
examination 
x 
- 
x 
- 
x 
- 
- 
x 
x 
x 
x 
x 
x 
xii 
xjj 
xa, ii 
xa, ii 
xa, ii 
xa, ii 
xa, ii 
- 
Ophthalmologic 
examinationii, kk 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
Table 4: 
Table of Events (Continued) 
Confidential and Proprietary 
50 
Approved v 1.10.0  930196084 1.0 
EDMS Doc. Number: 25746049 - 21742731 
JCAR017-BCM-001 Amendment 5: 12 Aug 2021 
 
 
 
 
Pretreatment Period 
Treatment Period 
Post-Treatment Period 
Survi 
val 
Fol- 
low- 
up 
Screen- 
ing 
Leuka- 
pheresis 
Pre- 
Treat- 
ment 
Evalua- 
tion 
LD 
Chemo- 
therapy 
JCAR017 
Infusion 
Follow-Up 
Study Day 
Up to 14 
days 
before 
leuka- 
pheresisdd 
Approx- 
imately 
35 days 
before 
Day 1 
Within 7 
days 
before LD 
chemo- 
therapy 
Start 5 
to 10 
days 
before 
Day 1ee 
1 
2 
3 
4 
8 
11 
15 
22 
29 
60 
90/ 
120jj 
180 
270 
365 545 
730 
(EOS) 
or ET 
q3m 
Visit Window (Days) 
- 
- 
- 
- 
- 
- 
- 
+1 
±1 
±1 ±2 ±2 
±2 
+14 
+14 
+35 +35 +35 +35 
+35 
±30 
IPI 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
MMSEhh 
- 
- 
x 
- 
x 
- 
- 
x 
x 
- 
x 
- 
x 
- 
xjj 
- 
- 
- 
- 
- 
- 
Vital signsd 
x 
xe 
x 
x 
xf 
x 
x 
x 
x 
x 
x 
x 
x 
- 
- 
- 
- 
- 
- 
- 
- 
12-lead ECG 
x 
- 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
MUGA scan/ECHO 
xz 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Viral serology 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Serum pregnancy 
x 
- 
xg 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
xjj 
x 
x 
x 
- 
- 
- 
HLA typing and donor 
chimerismh 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Urinalysis 
x 
- 
- 
- 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Leukapheresis 
- 
xi 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
LD chemotherapy 
- 
- 
- 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
JCAR017 infusiongg 
- 
- 
- 
- 
xj 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
Table 4: 
Table of Events (Continued) 
Confidential and Proprietary 
51 
Approved v 1.10.0  930196084 1.0 
EDMS Doc. Number: 25746049 - 21742731 
JCAR017-BCM-001 Amendment 5: 12 Aug 2021 
 
 
 
 
Pretreatment Period 
Treatment Period 
Post-Treatment Period 
Survi 
val 
Fol- 
low- 
up 
Screen- 
ing 
Leuka- 
pheresis 
Pre- 
Treat- 
ment 
Evalua- 
tion 
LD 
Chemo- 
therapy 
JCAR017 
Infusion 
Follow-Up 
Study Day 
Up to 14 
days 
before 
leuka- 
pheresisdd 
Approx- 
imately 5 
weeks 
before 
Day 1 
Within 7 
days 
before LD 
chemo- 
therapy 
Start 5 
to 10 
days 
before 
Day 1 ee 
1 
2 
3 
4 
8 
11 
15 
22 
29 
60 
90/ 
120jj 
180 
270 
365 
545 
730 
(EOS) 
or ET 
q3m 
Visit Window (Days) 
- 
- 
- 
- 
- 
- 
- 
+1 
±1 
±1 
±2 
±2 
±2 
+14 
+14 
+35 
+35 
+35 
+35 
+35 
±30 
Adverse events and 
concomitant medicationsb 
AEs related to protocol-mandated 
procedures and associated 
concomitant medications 
All AEs and associated concomitant medicationscc 
AEs related to JCAR017 and/or 
LD chemotherapy and associated 
concomitant medications 
- 
CT/MRI 
x 
- 
xk, l 
- 
- 
- 
- 
- 
- 
- 
- 
- 
xm 
xii 
xa, jj 
xa 
xa 
xa 
xa 
xa 
- 
Brain MRIll 
x 
- 
xk, l 
- 
- 
- 
- 
- 
- 
- 
- 
- 
xc 
xii 
xa, c, jj 
xa, c 
xa, c 
xa, c 
xa, c 
xa, c 
- 
CSF assessmentc 
x 
- 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
x 
xa, o, 
ii 
xa, o, jj 
xa, o 
xa, o 
xa, o 
xa, o 
xa, o 
- 
PET 
xn 
- 
xk, l 
- 
- 
- 
- 
- 
- 
- 
- 
- 
xm 
xii, p 
xp, jj 
xp 
xp 
xp 
xp 
xp 
- 
Tumor biopsy 
xq, z 
- 
- 
- 
- 
- 
- 
- 
- 
- 
x 
- 
- 
At progression 
- 
BMA/BMB 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
At time of CR in subjects with previous bone 
marrow involvement 
- 
Hematology 
x 
x 
x 
x 
x 
- 
- 
x 
x 
x 
x 
x 
x 
x 
xjj 
x 
x 
x 
x 
x 
- 
Coagulation 
- 
- 
x 
- 
x 
- 
- 
x 
x 
x 
x 
x 
x 
- 
- 
- 
- 
- 
- 
- 
- 
Chemistry 
x 
x 
x 
x 
x 
- 
- 
x 
x 
x 
x 
x 
x 
- 
- 
- 
- 
- 
- 
- 
- 
Creatinine clearance 
x 
- 
- 
xs 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
Inflammatory markers 
- 
- 
x 
- 
x 
- 
- 
x 
x 
x 
x 
xt 
xt 
- 
- 
- 
- 
- 
- 
- 
- 
Immunoglobulins 
- 
- 
x 
- 
- 
- 
- 
- 
- 
- 
x 
x 
x 
xu 
xu 
xu 
xu 
xu 
xu 
xu 
- 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
Table 4: 
Table of Events (Continued) 
Confidential and Proprietary 
52 
Approved v 1.10.0  930196084 1.0 
EDMS Doc. Number: 25746049 - 21742731 
JCAR017-BCM-001 Amendment 5: 12 Aug 2021 
 
 
 
 
Pretreatment Period 
Treatment Period 
Post-Treatment Period 
Survi 
val 
Fol- 
low- 
up 
Screen- 
ing 
Leuka- 
pheresis 
Pre- 
Treat- 
ment 
Evalua- 
tion 
LD 
Chemo- 
therapy 
JCAR01 
7 
Infusion 
Follow-Up 
Study Day 
Up to 14 
days 
before 
leuka- 
pheresisdd 
Approx- 
imately 5 
weeks 
before 
Day 1 
Within 7 
days 
before LD 
chemo- 
therapy 
Start 5 
to 10 
days 
before 
Day 1 ee 
1 
2 
3 
4 
8 
11 
15 
22 
29 
60 
90/ 
120jj 
180 
270 
365 
545 
730 
(EOS) 
or ET 
q3m 
Visit Window (Days) 
- 
- 
- 
- 
- 
- 
- 
+1 
±1 
±1 
±2 
±2 
±2 
+14 
+14 
+35 
+35 
+35 
+35 
+35 
±30 
EORTC QLQ-C30 
x 
- 
x 
- 
x 
- 
- 
- 
- 
- 
- 
- 
x 
x 
x 
x 
x 
x 
x 
x 
- 
EQ-5D-5L 
x 
- 
x 
- 
x 
- 
- 
- 
- 
- 
- 
- 
x 
x 
x 
x 
x 
x 
x 
x 
- 
FACT-LymS 
x 
- 
x 
- 
x 
- 
- 
- 
- 
- 
- 
- 
x 
x 
x 
x 
x 
x 
x 
x 
- 
Hospital resource 
utilization 
- 
- 
- 
at all time 
- 
Survival status 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
x 
RESEARCH SAMPLES 
Peripheral blood sample 
for soluble factorsff 
(plasma) 
x 
- 
x 
- 
xv 
- 
- 
x 
x 
x 
x 
x 
x 
- 
- 
- 
- 
- 
- 
- 
- 
Peripheral blood sample 
for immunogenicity 
(serum) 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
x 
- 
x 
x 
x 
x 
x 
x 
x 
x 
- 
Peripheral blood sample 
for immunogenicity 
(PBMC) 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
x 
- 
x 
x 
- 
- 
- 
- 
- 
- 
- 
Peripheral blood sample 
for PK by flow 
cytometrybb 
x 
- 
- 
- 
xv 
- 
- 
x 
x 
x 
x 
x 
x 
x 
xjj 
x 
x 
x 
x 
x 
- 
Peripheral blood sample 
for viral vector sequence 
PK by qPCRw 
x 
- 
- 
- 
xv 
- 
- 
x 
x 
x 
x 
x 
x 
x 
xjj 
x 
x 
x 
x 
x 
- 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
Table 4: 
Table of Events (Continued) 
Confidential and Proprietary 
53 
Approved v 1.10.0  930196084 1.0 
EDMS Doc. Number: 25746049 - 21742731 
JCAR017-BCM-001 Amendment 5: 12 Aug 2021 
 
 
 
 
Pretreatment Period 
Treatment Period 
Post-Treatment Period 
Survi 
val 
Fol- 
low- 
up 
Screen- 
ing 
Leuka- 
pheresis 
Pre- 
Treat- 
ment 
Evalua- 
tion 
LD 
Chemo- 
therapy 
JCAR017 
Infusion 
Follow-Up 
Study Day 
Up to 14 
days 
before 
leuka- 
pheresisdd 
Approx- 
imately 5 
weeks 
before 
Day 1 
Within 7 
days 
before LD 
chemo- 
therapy 
Start 5 
to 10 
days 
before 
Day 1 ee 
1 
2 
3 
4 
8 
11 
15 
22 
29 
60 
90/ 
120jj 
180 
270 
365 
545 
730 
(EOS) 
or ET 
q3m 
Visit Window (Days) 
- 
- 
- 
- 
- 
- 
- 
+1 
±1 
±1 
±2 
±2 
±2 
+14 
+14 
+35 
+35 
+35 
+35 
+35 
±30 
Peripheral blood sample 
for biomarkers (PBMC) 
x 
- 
- 
- 
- 
- 
- 
- 
- 
x 
- 
x 
x 
- 
x 
- 
- 
- 
- 
- 
Peripheral blood sample 
for biomarkers 
(Immunophenotyping) 
x 
x 
- 
- 
- 
- 
- 
- 
x 
- 
x 
x 
x 
x 
- 
x 
- 
- 
- 
- 
- 
Peripheral blood sample 
for RCL testing 
- 
x 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
x 
x 
- 
x 
- 
x 
- 
Abbreviations: AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; CNS = central nervous system; CR = complete response CRF = case report form; 
CSF = cerebrospinal fluid; CT = computed tomography; DLCO = diffusion capacity of carbon monoxide; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern 
Cooperative Oncology Group; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer – Quality of Life C30 questionnaire; EOS = end of study; EQ- 
5D-5L = European Quality of Life-5 Dimensions health state classifier to 5 Levels; ET = early termination; FACT-LymS = Functional Assessment of Cancer Treatment- 
Lymphoma “Additional concerns” subscale; FEV1 = forced expiratory volume in one second; GVHD = graft-versus-host disease; HCT = hematopoietic cell transplantation; HCT- 
CI = HCT-specific comorbidity index; HLA = human leukocyte antigen; HSCT = hematopoietic stem cell transplantation; ICF = informed consent form; IPI = International 
Prognostic Index; IV = intravenous; LD = lymphodepleting; MMSE = Mini Mental State Examination; MRI = magnetic resonance imaging; MUGA = multigated acquisition; 
PBMC = peripheral blood mononuclear cell; PCNSL = primary central nervous system lymphoma; PCR = polymerase chain reaction; PD = progressive disease; PET = positron 
emission tomography; PK = pharmacokinetic; q3m = every 3 months; qPCR = quantitative polymerase chain reaction; RCL = replication-competent lentivirus; TNE = transplant 
not eligible. 
a Not required after PD/relapse or subsequent anticancer treatment. 
b Please refer to Section 6.3 for the assessments that will be performed in subjects who have received subsequent anticancer treatment. 
c For Cohort 1, 2, 3, 4, and 7: Required at screening for subjects with suspected or confirmed CNS involvement. Subsequent assessments are only required for subjects with 
confirmed CNS involvement. For Cohort 5: Required at screening and at time of pre-treatment evaluation unless medically contraindicated. For subjects without CSF 
involvement, repeated evaluation is not required in absence of interval symptoms suggestive of leptomeningeal dissemination. 
d Subjects who require hospitalization should have vital signs assessed daily. Minimum and maximum values within a 24-hour period should be recorded on the appropriate CRF. 
e Vital signs should be taken before and after leukapheresis. 
f Measured within 15 minutes prior to the first JCAR017 administration and approximately every 15 minutes thereafter for the first hour, and hourly for the next 2 hours. If the 
subject's vital signs are not stable 4 hours following the final IV administration, vital signs should be monitored as clinically indicated until stable. 
g Within 48 hours prior to starting LD chemotherapy. 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
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h Data from local testing will be collected for those subjects with prior allogeneic HSCT. 
i Should be scheduled as soon as possible after meeting eligibility criteria. 
j 2 to 7 days after completion of LD chemotherapy. 
k For subjects who receive anticancer treatment for disease control while JCAR017 is being manufactured, restaging must be performed after completion of the intervening 
anticancer treatment and as close as possible to the start of lymphodepleting chemotherapy (recommended within 7 to 14 days prior to start). For Cohort 4, restaging is 
mandatory after 2 cycles of induction to check for complete metabolic response. 
l Recommended within 14 days prior to start of LD chemotherapy. Not required if intervening anticancer treatment was not given and if scans were done at the study site for 
screening or within 6 weeks prior to the start of LD chemotherapy. 
m Once between Days 29 to 35. Not required for subjects in Cohort 5 without systemic involvement at screening. 
n PET scan to confirm the presence of PET-positive lymphoma or, for Cohort 5, to assess potential systemic involvement in subjects with PCNSL. PET scan may be performed 
more than 30 days prior to screening if no intervening anticancer treatments have been performed or if the Investigator confirms continued disease presence 
o CSF assessment not required for subjects in CR unless suspicion for CNS relapse. 
p Not required for subjects in Cohort 5 without systemic involvement at screening, subjects in CR, subjects who have progressed, or after institution of additional anticancer 
treatment. A PET scan should be performed to verify PD. 
q Collection of tissue from latest archived tumor biopsy (block or slides) for tumor evaluation. If archival sample is before most recent relapse, a new tumor biopsy is mandated to 
confirm diagnosis. Note: If the subject did not experience CR since last biopsy, the most recent biopsy will be considered adequate to participate in the trial. For subjects with 
PCNSL, at a minimum, corresponding pathology report is required if archival tumor material is not available and repeated biopsy not feasible. 
r For subjects with accessible disease. 
s First day of LD chemotherapy only. 
t If clinically indicated. 
u Not required for subjects with documented B-cell recovery without recent use of intravenous immunoglobulin. 
v Pre-infusion. 
w At any time point ≥ 12 months after JCAR017 infusion, if persistence vector sequence is detected in ≥ 1% of cells, the pattern for vector integration sites will be analyzed. If 
integration pattern suggests a predominant integration site, a repeat analysis will be conducted within 3 months and further studies including insertion site analysis will be 
performed. 
x For TNE subjects in Cohorts 2 and 3 only. 
y The subject must continue to meet pretreatment eligibility criteria pertaining to adequate organ function, active infections, pregnancy, and washout of prior therapy before 
initiation of LD chemotherapy. 
z Performed within 4 weeks prior to leukapheresis. 
aa Including GVHD assessment (if applicable). 
bb Not required at Japanese sites. 
cc For subjects receiving LD chemotherapy but not JCAR017, all AEs and associated concomitant medications will be collected for 30 days following the last dose of LD 
chemotherapy. 
dd Screening procedure as standard of care within 30 days prior to signing the ICF may be used to evaluate study eligibility based on discussion with Celgene. 
ee Assessments to be performed each day before administration of LD chemotherapy (refer to Section 6.2.1). 
ff Soluble factors, such as cytokines and chemokines. 
gg Prior to dose, it must be confirmed that the subject meets criteria for JCAR017 infusion (refer to Section 6.2.2). 
hh If subjects develop neurologic symptoms suspicious of and/or diagnosed as neurologic toxicity, subjects will have daily MMSE exams (see Appendix D) until resolution of 
symptoms, unless the subject is medically incapacitated and/or medically unable to complete the MMSE. If exceptional circumstances preclude the continued administration of 
outcome measures using planned modalities, then alternate administration methods (eg, abbreviated version of the MMSE questionnaire) may be used. If immune effector cell- 
associated encephalopathy (ICE) scores are taken per institutional practice, those scores should be recorded as well. 
ii For PCNSL subjects in Cohort 5 only (refer to Section 6.5). 
jj For PCNSL subjects in Cohort 5 only: all efficacy assessments should be performed at Day 120 instead of Day 90 (refer to Section 6.5) and only other study procedures and 
research samples marked with jj are repeated at Day 90 and at Day 120. 
kk Only to be repeated after screening if new symptom(s) or suspicion occurs. 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
55 
Approved v 1.10.0  930196084 1.0 
EDMS Doc. Number: 25746049 - 21742731 
JCAR017-BCM-001 Amendment 5: 12 Aug 2021 
 
 
ll For Cohort 1, 2, 3, 4, and 7, brain MRI is required at screening for subjects with suspected or confirmed CNS involvement. Subsequent assessments are only required for 
subjects with confirmed CNS involvement. 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
EDMS Doc. Number: 25746049 - 21742731 
Confidential and Proprietary 
56 
JCAR017-BCM-001 Amendment 5: 12 Aug 2021 
930196084 1.0 
Approved v 1.10.0 
 
 
 
6. 
PROCEDURES 
Any questions regarding the protocol should be directed to the Medical Monitor(s) or 
designee. 
6.1. 
Pretreatment Period 
6.1.1. 
Screening 
Screening may begin up to 14 days prior to leukapheresis when the subject signs the IRB/EC- 
approved informed consent form and continues until enrollment (ie, meeting eligibility 
requirements; or screen failure is determined). Where applicable, institutional decision boards 
(eg, multidisciplinary tumor boards, Réunion de concertation pluridisciplinaire [RCP]) should 
be involved in subject selection. If a subject has had a screening procedure as standard of care 
within 30 days prior to signing the ICF, it may be used to evaluate study eligibility based on 
discussion with Celgene. The following assessments will be performed during the screening 
period, prior to enrollment: 
• Obtain informed consent 
• Assess eligibility per inclusion/exclusion criteria. All inclusion/exclusion criteria 
must be met in order for subjects to enroll in the study 
• Obtain medical history, including: Disease diagnosis and history, HSCT history, 
chemotherapy, radiation and surgical history, history of prior gene therapy. May 
include history of toxicities related to prior treatments and allergies 
• Physical examination, including routine neurologic examination, height, weight, 
and vital signs (blood pressure, body temperature, respirations, heart rate, and 
oxygen saturation via pulse oximetry) and GVHD assessment (if applicable) 
• ECOG performance status assessment 
• IPI status 
• For TNE subjects in Cohorts 2 and 3 only: HCT-CI score (Sorror, 2005) (see 
Appendix G) and Frailty Scale (Larocca, 2016) (see Appendix H) 
• For TNE subjects in Cohorts 2 and 3 only: Pulmonary function test to assess 
DLCO (adjusted for hemoglobin concentration using the Dinakara equation) and 
forced expiratory volume in one second (FEV1) 
• MUGA scan or cardiac echocardiogram (ECHO) (performed within 4 weeks prior 
to leukapheresis) for LVEF 
• 12-lead electrocardiogram (ECG) 
• Ophthalmologic examination (for subjects with PCNSL only) 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Chemistry 
− Hematology 
− Viral serology 
− Serum ß-HCG pregnancy test on women of child-bearing potential 


JCAR017 
Protocol JCAR017-BCM-001 
Celgene Corporation 
EDMS Doc. Number: 25746049 - 21742731 
Confidential and Proprietary 
57 
JCAR017-BCM-001 Amendment 5: 12 Aug 2021 
930196084 1.0 
Approved v 1.10.0 
 
 
− Determination of creatinine clearance (eGFR by Cockcroft-Gault, see 
Appendix F) 
• Urinalysis 
• PET scan to confirm the presence of PET-positive lymphoma or for Cohort 5, to 
assess potential systemic involvement in subjects with PCNSL. PET scan may be 
performed more than 30 days prior to screening if no intervening anticancer 
treatments have been performed or if the Investigator confirms continued disease 
presence 
• Computed tomography (CT)/magnetic resonance imaging (MRI) (chest, neck, 
abdomen, pelvis) 
• Brain MRI required only for subjects with suspected or confirmed CNS 
involvement 
• Lumbar puncture or Ommaya reservoir tap for CSF assessment required only for 
subjects with suspected or confirmed CNS involvement 
• Collection of tissue from latest archived tumor biopsy (block or slides) for tumor 
evaluation. If archival sample is before most recent relapse, a new tumor biopsy is 
mandated to confirm diagnosis for subjects with accessible disease 
• Bone marrow aspirate and biopsy 
• Administration of EQ-5D-5L and EORTC QLQ-C30 questionnaires and FACT- 
LymS 
• Research samples (see the JCAR017-BCM-001 laboratory manual for details): 
− Immunogenicity 
− Pharmacokinetics (PK) by flow cytometry (not required at Japanese sites) 
− Viral vector sequence PK by qPCR 
− Biomarkers 
• Local laboratory assessments (see Appendix E) 
− Human leukocyte antigen (HLA) typing and donor chimerism for subjects 
who had previous allogeneic HSCT (not required if HLA typing results are 
available from previous testing) 
• Record all AEs related to protocol-mandated procedures and associated 
concomitant medications 
6.1.2. 
Leukapheresis (approximately 35 days prior to JCAR017 infusion) 
Leukapheresis should be scheduled in coordination with the Celgene as soon as possible after 
the subject has completed screening and eligibility requirements are met. Prior to 
leukapheresis, appropriate protocol mandate washout periods are to be followed (see 
Table 5). Venous access is required for leukapheresis and should be determined according to 
institutional practice. Should a technical issue arise during the procedure or in the immediate 


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processing of the product such that it cannot be used for JCAR017 production, a second 
collection procedure may be performed. 
The following assessments will be conducted prior to leukapheresis: 
• Chemistry 
• Hematology. CBC with differential on the day of leukapheresis (or within 24 
hours prior) 
• Vital signs (blood pressure, body temperature, respirations, heart rate, and oxygen 
saturation via pulse oximetry) (also after leukapheresis) 
• ECOG performance status assessment 
• Research samples (see the JCAR017-BCM-001 laboratory manual for details): 
− Biomarkers (Immunophenotyping) 
− RCL testing 
• Record all AEs related to protocol-mandated procedures and associated 
concomitant medications 
• Patient interview (see Table 7) 
 
Table 5: 
Washout Periods Prior to Leukapheresis and Prior to Lymphodepleting 
Chemotherapy 
 
Treatment 
Washout 
Prior to 
Leukapheresis 
Prior to Lymphodepleting 
Chemotherapy 
Systemic Therapy 
Alemtuzumab 
6 months 
Fludarabine 
3 months 
7 days 
Cladribine 
3 months 
7 days 
Experimental agents 
4 weeks/3 half-lives 
(whichever is greater) 
Not applicable 
Lymphotoxic chemotherapeutic agents (eg, 
cyclophosphamide , ifosfamide, 
bendamustine) 
2 weeks 
7 days 
Therapeutic doses of corticosteroids 
(defined as > 20 mg/day prednisone or 
equivalent) 
7 days 
Not applicable 
Cytotoxic chemotherapeutic agents not 
considered lymphotoxic (eg, doxorubicin, 
vincristine, gemcitabine, oxaliplatin, 
carboplatin, etoposide) 
7 days 
Rituximab 
7 days 
Oral chemotherapeutic agents (eg, 
lenalidomide and ibrutinib) 
3 half-lives 


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Table 5: 
Washout Periods Prior to Leukapheresis and Prior to Lymphodepleting 
Chemotherapy (Continued) 
 
Treatment 
Washout 
Prior to Leukapheresis 
Prior to Lymphodepleting 
Chemotherapy 
Intrathecal 
Dexamethasone, methotrexate, cytosine 
arabinoside 
7 days 
Radiation Therapy 
Radiation, multiple lesions 
6 weeks 
7 days (not allowed for 
Cohort 5) 
Radiation, single lesion, if additional non- 
irradiated PET-positive lesions are present 
2 weeks 
6.1.3. 
Anticancer Treatments between Leukapheresis and Lymphodepleting 
Chemotherapy 
If necessary, anticancer treatment is allowed for disease control while JCAR017 is being 
manufactured (ie, after leukapheresis and prior to LD chemotherapy). Low-dose 
chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2) is allowed if 
completed at least 7 days prior to the start of LD chemotherapy. If other agents are used, the 
washout periods noted in the exclusion criteria (see Table 5) must be met. The use of 
therapeutic agents with little/no evidence in the scientific literature for NHL should be 
discussed with Celgene. Except for Cohort 5 (PCNSL), local radiation is allowed to a single 
lesion or subset of lesions if other non-irradiated PET-positive lymphoma lesions are present. 
If anticancer treatment is necessary during this time, the pretreatment PET and CT/MRI 
assessments and other pretreatment study procedures (see Section 6.1.4) must be performed 
after the anticancer treatment has been completed. The subject must continue to have PET- 
positive disease and meet pretreatment eligibility criteria pertaining to adequate organ 
function, active infections, pregnancy, and washout of prior therapy before initiation of LD 
chemotherapy. 
6.1.4. 
Pretreatment Evaluation (following enrollment and within 7 days prior to 
lymphodepleting chemotherapy) 
The following assessments will be conducted: 
• For subjects who receive anticancer treatment for disease control while JCAR017 
is being manufactured: 
Restaging CT/MRI (chest, neck, abdomen, pelvis) and PET must be performed 
after completion of the intervening anticancer treatment and as close as possible to 
the start of LD chemotherapy (recommended within 7 to 14 days prior to start). 
For Cohort 4, restaging is mandatory after 2 cycles of induction to check for 
complete metabolic response. 
• For subjects who did not receive anticancer treatment control while JCAR017 is 
being manufactured: 


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If no scans were done at the study site for screening and within 6 weeks prior to 
the start of LD chemotherapy, CT/MRI and PET scans must be performed 
(recommended within 14 days prior to start of LD chemotherapy). 
• Brain MRI required only for subjects with confirmed CNS involvement 
• Lumbar puncture or Ommaya reservoir tap for CSF assessment required only for 
subjects with confirmed CNS involvement (Cohort 5 subjects must repeat CSF 
assessment at time of pre-treatment evaluation unless medically contraindicated) 
The following assessments will be conducted within 7 days prior to starting LD 
chemotherapy and after any anticancer treatment received for tumor control: 
• Confirm inclusion/exclusion (as defined in Section 4.2 and Section 4.3) and study 
pretreatment eligibility criteria: 
− PET positive disease 
− Adequate organ function 
− Washout of prior therapy 
− No uncontrolled bacterial, viral or fungal infection 
In case of suspected infection, subject should be treated and LD chemotherapy 
postponed until the active infection has resolved. 
Physical examination, including routine neurologic examination, weight, and vital 
signs (blood pressure, body temperature, respirations, heart rate, and oxygen 
saturation via pulse oximetry) and GVHD assessment (if applicable) 
• ECOG performance status assessment 
• Mini Mental State Examination (MMSE; see Appendix D) and ICE score (if 
performed) 
• 12-lead ECG 
• Research samples (see the JCAR017-BCM-001 laboratory manual for details): 
− Biomarkers (Soluble factors) 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Chemistry 
− Hematology 
− Coagulation 
− Inflammatory markers 
− Immunoglobulins 
− Serum ß-HCG pregnancy test on all women of child-bearing potential (within 
48 hours prior to starting LD chemotherapy) 
• Record all AEs related to protocol-mandated procedures and associated 
concomitant medications 
• Administration of EQ-5D-5L and EORTC QLQ-C30 questionnaires and FACT- 
LymS 


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• Patient interview (see Table 7) 
6.2. 
Treatment Period 
Subjects must be clinically stable and must have recovered from prior toxicities, to receive 
LD chemotherapy and proceed to JCAR017 infusion. Neither LD chemotherapy nor 
JCAR017 treatment should be administered if there is a worsening of performance status 
compared to initial eligibility criteria, rapid clinical deterioration, or evidence of rapidly 
progressive disease. Note: Subjects who are transplant not eligible or have PCNSL may have 
ECOG 2, however, must be clinically stable, recover from prior toxicities, and not have 
evidence of rapidly progressive disease or rapid clinical deterioration prior to receiving LD 
chemotherapy or JCAR017 infusion. 
6.2.1. 
Lymphodepleting Chemotherapy (start 5 to 10 days prior to JCAR017 
infusion) 
Upon notification from Celgene that JCAR017 will be available, LD chemotherapy should be 
initiated so as to finish at least two days prior to JCAR017 infusion. Lymphodepleting 
chemotherapy can start 5 to 10 days prior to JCAR017 infusion. Please see Section 7.3.1 for 
the recommended administration. Subjects must be evaluated for evidence of ongoing 
infections prior to the LD chemotherapy to be started. In case of suspicion of infection, 
subject should be treated accordingly and LD chemotherapy postponed until infection 
resolution. 
Subjects should not experience a significant worsening in clinical status compared to the 
initial eligibility criteria that would, in the opinion of the treating physician, increase the risk 
of adverse events associated with lymphodepleting chemotherapy or exclude them from 
treatment with JCAR017 (see Section 6.2.2). 
The following assessments will be performed on each day before administration of LD 
chemotherapy: 
• Vital signs 
• ECOG performance status assessment 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Determination of creatinine clearance (eGFR by Cockcroft-Gault, see 
Appendix F) (required only on first day of LD chemotherapy) 
− Chemistry 
− Hematology 
• Record all AEs and associated concomitant medications 
• Hospital resource utilization 
6.2.2. 
JCAR017 Administration: Day 1 
Subjects will receive JCAR017 infusion 2 to 7 days after completion of LD chemotherapy. 
The first 10 subjects treated with JCAR017 respectively in Europe and in Japan must be 
hospitalized for a minimum of 14 days after JCAR017 infusion. 


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Subjects who do not have adequate social support outside of the hospital or do not have 
reliable transportation to the clinic for scheduled evaluations or emergencies post-therapy 
should be considered for hospitalization for the first 14 days of treatment. 
Subjects should not experience a significant worsening in clinical status compared to initial 
eligibility criteria that would, in the opinion of the treating physician, increase the risk of 
adverse events associated with JCAR017 infusion. Subjects who meet at least one of the 
following criteria on the day of scheduled JCAR017 infusion should have JCAR017 
administration delayed: 
• Suspected or active systemic infection 
• Onset of fever ≥ 38°C/100.4°F, not related to underlying disease 
• Presence of progressive radiographic abnormalities on chest x-ray, or requirement for 
supplemental oxygen to keep saturation greater than 91% 
• Cardiac arrhythmia not controlled with medical management 
• Hypotension requiring vasopressor support 
• New-onset or worsening of other non-hematologic organ dysfunction ≥ Grade 3 
• Taking any of the prohibited medications as described in Section 8.2 
• Progressive vascular tumor invasion, thrombosis, or embolism 
• Venous thrombosis or embolism not managed on a stable regimen of anticoagulation 
Subjects with active infection must have JCAR017 infusion postponed until the active 
infection has resolved (subjects with suspected/ active infection must have negative culture 
for at least 24 hours on appropriate antibiotics or negative rapid viral panel). Subjects with 
organ toxicities may not receive JCAR017 until the organ toxicities have recovered to ≤ 
Grade 2. In case of delayed infusion, lymphodepleting chemotherapy may need to be 
repeated after discussion with the Sponsor (see Section 6.2.1). 
In the event that a subject experiences any of the above, the Sponsor must be contacted and 
discussion regarding delay of treatment must occur. 
The following assessments are to be performed prior to the JCAR017 infusion: 
• Physical examination 
• Weight 
• Vital signs (measured within 15 minutes prior to the first JCAR017 
administration) 
• ECOG performance status assessment 
• Routine neurologic examination 
• MMSE (see Appendix D) and ICE score (if performed). 
• Record all AEs and associated concomitant medications 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Chemistry 
− Hematology 


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− Coagulation 
− Inflammatory markers 
• Urinalysis 
• Research samples (pre-infusion; see the JCAR017-BCM-001 laboratory manual): 
− PK by flow cytometry (not required at Japanese sites) 
− Viral vector sequence PK by qPCR 
− Biomarkers (Soluble factors) 
• Administration of EQ-5D-5L and EORTC QLQ-C30 questionnaires and FACT- 
LymS 
• Patient interview (see Table 7) 
• JCAR017 premedication (see Section 7.3.2) 
• Hospital resource utilization 
Treatment administration will be registered in the interactive response technology (IRT) 
system. 
• After infusion, vital signs will be repeated approximately every 15 minutes for the 
first hour, and hourly for the next 2 hours. If the subject’s vital signs are not stable 
4 hours following the final IV administration, vital signs should be monitored as 
clinically indicated until stable. 
6.2.3. 
Days 2 and 3 
• Vital signs 
• Physical examination 
• Record all AEs and associated concomitant medications 
• Hospital resource utilization 
6.2.4. 
Day 4 (+1 day) 
• Vital signs 
• Routine neurologic examination 
• Physical examination 
• MMSE (see Appendix D and Section 6.4.4) and ICE score (if performed) 
• Record all AEs and associated concomitant medications 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Chemistry 
− Hematology 
− Coagulation 
− Inflammatory markers 
• Research samples (see the JCAR017-BCM-001 laboratory manual): 


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− PK by flow cytometry (not required at Japanese sites) 
− Viral vector sequence PK by qPCR 
− Biomarkers (Soluble factors) 
• Hospital resource utilization 
6.2.5. 
Day 8 (±1 day) 
• Physical examination 
• Vital signs 
• ECOG performance status assessment 
• Routine neurologic examination 
• MMSE (see Appendix D and Section 6.4.4) and ICE score (if performed) 
• Record all AEs and associated concomitant medications 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Chemistry 
− Hematology 
− Coagulation 
− Inflammatory markers 
• Research samples (see the JCAR017-BCM-001 laboratory manual): 
− PK by flow cytometry (not required at Japanese sites) 
− Viral vector sequence PK by qPCR 
− Biomarkers (Soluble factors, immunophenotyping) 
• Hospital resource utilization 
6.2.6. 
Day 11 (±1 day) 
• Vital signs 
• Physical examination 
• Routine neurologic examination 
• Record all AEs and associated concomitant medications 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Chemistry 
− Hematology 
− Coagulation 
− Inflammatory markers 
• Research samples (see the JCAR017-BCM-001 laboratory manual): 
− PK by flow cytometry (not required at Japanese sites) 


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− Viral vector sequence PK by qPCR 
− Biomarkers (Soluble factors) 
• Hospital resource utilization 
6.2.7. 
Days 15, 22, and 29 (±2 days) 
• Physical examination 
• Vital signs 
• ECOG performance status assessment 
• Routine neurologic examination 
• Brain MRI for subjects with confirmed CNS involvement is required on Day 29 
• MMSE required on Days 15 and 29 (see Appendix D and Section 6.4.4) and ICE 
score (if performed) 
• Administration of EQ-5D-5L and EORTC QLQ-C30 questionnaires and FACT- 
LymS required on Day 29 
• Record all AEs and associated concomitant medications 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Chemistry 
− Hematology 
− Coagulation 
− Inflammatory markers required on Day 15 (required on Days 22 and 29 if 
clinically indicated) 
− Immunoglobulins 
• Research samples (see the JCAR017-BCM-001 laboratory manual): 
− Immunogenicity required on Days 15 and 29 
− PK by flow cytometry (not required at Japanese sites) 
− Viral vector sequence PK by qPCR 
− Biomarkers (PBMC required on D15 and D29, Soluble factors and 
Immunophenotyping required on D15, 22 and 29) 
• Response evaluation by PET scan and CT/MRI (once between Days 29 to 35). 
PET-CT does not need to be repeated in the absence of systemic disease at 
baseline or suspicion of systemic PD for subjects in Cohort 5. 
• Tumor biopsy for subjects with accessible disease required on Day 15 
• Lumbar puncture or Ommaya reservoir tap for CSF assessment for subjects with 
confirmed CNS involvement at pre-treatment is required on Day 29 
• Patient interview required on Day 29 (see Table 7) 
• Hospital resource utilization 


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6.3. 
Post-Treatment Period (Follow-up) 
All subjects who received any JCAR017 infusion, including subjects with progressive 
disease, should complete the post-treatment period visits at approximately 2, 3 (4 month for 
subjects with PCNSL), 6, 9, 12, 18, and 24 months (end of study [EOS]) after JCAR017 
infusion for disease status and survival, unless otherwise specified. 
The following assessments will be performed in subjects who have not received subsequent 
anticancer treatment following JCAR017 infusion: 
• Physical examination required on Months 2, 3 (and on month 4 for subjects with 
PCNSL only), 6, 9, 12, and 24 (after PD/relapse: required on Months 12 and 24) 
• Routine neurologic examination required for all subjects on Month 3 (except for 
subjects with PCNSL). For subjects with PCNSL required on Months 2, 4, 6, 9, 
12, 18, and 24 (after PD/relapse: required on Month 2) 
• Brain MRI for subjects with confirmed CNS involvement is required on Months 
3, 6, 9, 12, 18 and 24 (not required after PD/relapse). For subjects with PCNSL 
required on Months 2, 4, 6, 9, 12, 18, and 24 (not required after PD/relapse) 
• PET scan required on Months 3, 6, 9, 12, 18, and 24 or to verify PD (not required 
for subjects in CR or after PD/relapse). For subjects with PCNSL required on 
Months 2, 4, 6, 9, 12, 18, and 24 (not required for subjects without systemic 
involvement at screening, subjects in CR or after PD/relapse) 
• CT/MRI scan required on Months 3, 6, 9, 12, 18, and 24 (not required after 
PD/relapse). For subjects with PCNSL required on Months 2, 4, 6, 9, 12, 18, and 
24 (not required after PD/relapse) 
• Lumbar puncture or Ommaya reservoir tap for CSF assessment for subjects with 
confirmed CNS involvement is required on Months 3, 6, 9, 12, 18, and 24 (not 
required for subjects in CR if no suspicion of CNS relapse and after PD/relapse). 
For subjects with PCNSL required on Months 2, 4, 6, 9, 12, 18, and 24 (not 
required for subjects with negative CSF at pre-treatment visit, in CR if no 
suspicion of CNS relapse and after PD/relapse). 
• MMSE and ICE score (if performed) required on Month 3 (and on Month 4 for 
subjects with PCNSL only) (see Appendix D and Section 6.4.4) 
• ECOG performance status assessment required on Months 2, 3 (and on month 4 
for subjects with PCNSL only), 6, 9, 12, 18, and 24 (not required after PD/relapse) 
• Administration of EQ-5D-5L and EORTC QLQ-C30 questionnaires and FACT- 
LymS 
• Collection of peripheral blood samples for clinical laboratory evaluations: 
− Hematology required on Months 2, 3 (and on month 4 for subjects with 
PCNSL only), 6, 9, 12, 18, and 24 
− Immunoglobulins required on Months 2, 3, 6, 9, 12, 18, and 24 (not required if 
B-cell recovery documented without recent administration of intravenous 
immunoglobulins [IVIG]) 
− Serum ß-HCG pregnancy test on all women of child-bearing potential required 
on Month 3, 6, 9 and 12 (and on Month 4 only for subjects with PCNSL) 


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• Research samples (see the JCAR017-BCM-001 laboratory manual for details): 
− RCL sample collection required on Months 3, 6, 12, and 24 
− Immunogenicity 
− PK by flow cytometry (not required at Japanese sites) 
− Viral vector sequence PK by qPCR sample collection 
− Biomarkers (PBMC and Immunophenotyping) required on Months 2 and 6 
• Record all AEs and associated concomitant medications until 90 days after 
JCAR017 infusion and afterwards all AEs related to JCAR017 and/or LD 
chemotherapy and associated concomitant medications 
• Patient interview (see Table 7) 
• Hospital resource utilization 
The following assessments will be performed in subjects who have received subsequent 
anticancer treatment: 
• Collection of all anticancer treatment since JCAR017 infusion 
• Physical examination required on Months 12 and 24 
• Immunoglobulins required on Months 3, 6, 9, 12, 18, and 24 (not required if B- 
cell recovery documented without recent administration of IVIG) 
• RCL sample collection required on Months 3, 6, 12, and 24 
• Viral vector sequence PK by qPCR sample collection 
• Pregnancy test at Month 3, if applicable 
• Record AEs and associated concomitant medications according to Section 10.1 
• Patient interview (see Table 7) 
• Hospital resource utilization 
Note: Subjects who receive HSCT post-JCAR017 (but no other anticancer treatment) should 
continue to undergo scans, unless they have demonstrated PD prior to transplant. A PET scan 
should be performed to verify PD. 
6.3.1. 
Unscheduled Evaluations 
If the Investigator feels that a subject needs to be evaluated at a time other than the protocol- 
specified visit, the subject may be asked to come in to the clinic for an unscheduled 
evaluation. The following assessments may be performed, as appropriate: 
• Physical examination 
• Vital signs 
• ECOG performance status assessment 
• MMSE (see Appendix D and Section 6.4.4) and ICE score (if performed) 
• Clinical laboratory evaluations 
• PET scan 


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• CT/MRI scan 
• Tumor biopsy (see the JCAR017-BCM-001 laboratory manual) 
• Bone marrow aspirate and biopsy 
• CSF assessment 
• Ophthalmologic examination 
• RCL peripheral blood 
• Research samples (see the JCAR017-BCM-001 laboratory manual): 
− Immunogenicity 
− PK by flow cytometry. If a subject has received additional non-lymphotoxic 
anticancer treatment, radiation, or surgery after progressive disease PK 
samples may be collected every 1 to 2 weeks (not applicable at Japanese sites). 
− Viral vector sequence PK by qPCR 
− Biomarkers 
• Hospital resource utilization 
Additionally, if the Investigator requests any of the following procedures, research samples 
may be collected, when possible: 
• Lumbar puncture or Ommaya reservoir tap for CSF assessment 
• Pleural, peritoneal, or other relevant fluid sampling 
• Tissue sampling 
• Autopsy 
6.3.2. 
Assessments upon Progressive Disease 
The following assessments will be performed as soon as possible after progressive disease: 
• Tumor biopsy, if clinically feasible (see the JCAR017-BCM-001 laboratory 
manual) 
• Research samples (see the JCAR017-BCM-001 laboratory manual): 
− Immunogenicity 
− PK by flow cytometry (not required at Japanese sites) 
− Viral vector sequence PK by qPCR 
− Biomarkers 
6.3.3. 
Assessment upon Complete Response 
For subjects with previous bone marrow involvement, a bone marrow aspirate and biopsy 
will be performed upon achieving of a complete response. 
6.3.4. 
Assessments at Time of Death 
In case an autopsy is performed and there is a safety concern for which a tissue analysis is 
needed, pertinent tissue samples will be collected if feasible, for central analysis of markers 


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related to safety when consent has been obtained from the subject and as allowed by local 
regulation. 
6.3.5. 
Early Withdrawal 
If a subject voluntarily withdraws prematurely from the study, a visit will be scheduled as 
soon as possible, and all of the assessments listed for the 24 month (EOS) visit will be 
performed. 
6.3.6. 
Survival Follow-Up 
After EOS visit or time of withdrawal, all enrolled subjects will be followed for survival 
every 3 months (± 30 days) until last subject last visit. Additional survival follow-up 
information will be collected in the context of the LTFU protocol for all subjects who 
received JCAR017. 
6.3.7. 
Long-Term Follow-Up 
Because this protocol involves gene transfer, long-term follow-up for lentiviral vector safety, 
disease status, and survival will continue on this protocol until 24 months after last infusion 
of JCAR017, regardless of disease status, and rolled over to a separate LTFU protocol 
thereafter for up to 15 years after JCAR017 infusion. 
All subjects who either complete the primary follow-up period specified in this protocol or 
who prematurely withdraw after JCAR017 infusion will be asked to enroll in the LTFU 
protocol at the EOS visit or at the time of withdrawal, respectively. A separate informed 
consent form will be provided for the LTFU protocol. Subjects who do not consent to 
participate in the LTFU protocol will be followed for survival through public record if 
permitted by local regulations. 
6.4. 
Safety Assessments 
6.4.1. 
Physical Examination 
A physical examination should include assessments of the following body parts/systems: 
abdomen, extremities, heart, lungs, and neurologic. In addition, symptom-directed exams 
should be performed. 
6.4.2. 
Vital Signs 
Vital signs include temperature, respiratory rate, heart rate and blood pressure. SaO2 will be 
assessed by pulse oximetry. Refer to Table 4, and Sections 6.2.2 and Section 7.3.4 for more 
details. 
6.4.3. 
Height and Weight 
Height in centimeters (cm) or inches (in) and body weight to the nearest kilogram (kg) in 
indoor clothing, but without shoes will be measured according to Table 4. 
6.4.4. 
Routine Neurologic and Mini Mental State Examinations 
A routine neurologic examination should include, at minimum, a physical examination to 
assess cranial nerves, motor and sensory skills, coordination and balance. The MMSE (see 
Appendix D) may be administered by an appropriately trained provider (ie, physician, nurse); 
a neurologist is not required. If exceptional circumstances preclude the continued 


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administration of outcome measures using planned modalities, then alternate administration 
methods (eg, abbreviated version of the MMSE questionnaire) may be used. Efforts should 
be made to have the same provider perform the MMSE on a given subject to maintain 
consistency of assessment. If subjects develop neurologic symptoms suspicious of and/or 
diagnosed as neurologic toxicity, subjects will have a daily MMSE until resolution of 
symptoms, unless the subject is medically incapacitated and/or medically unable to complete 
the MMSE. If immune effector cell-associated encephalopathy (ICE) scores are taken per 
institutional practice, those scores should be recorded as well. 
6.4.5. 
Cerebrospinal Fluid Assessment and Central Nervous System Symptom 
Assessment 
For Cohort 1, 2, 3, 4 and 7, Cerebrospinal fluid assessments should be performed for subjects 
with suspected or confirmed CNS involvement (if CNS involvement is suspected CNS 
imaging should also be performed) at screening. Repeat CSF at pretreatment evaluation and 
after JCAR017 administration is only required for subjects with confirmed CNS involvement, 
and should be performed until complete response. Thereafter, repeat CSF only in subjects 
with suspicion of CNS relapse (Table 4). For Cohort 5 CSF is required at screening and at 
time of pre-treatment evaluation, unless medically contraindicated. For subjects without CSF 
involvement, repeated evaluation is not required in the absence of interval symptoms 
suggestive of leptomeningeal dissemination. 
Cerebrospinal fluid will be analyzed for cell count and differential cytology (see the 
JCAR017-BCM-001 laboratory manual for instructions on sending a sample for JCAR017 
testing). Cerebrospinal fluid cultures (bacterial, fungal, viral) should be performed as 
clinically indicated for suspicion of infection. 
6.4.6. 
Eastern Cooperative Oncology Group Performance Status 
Eastern Cooperative Oncology Group performance status (see Appendix B) will be used to 
evaluate subject eligibility at screening and will be assessed throughout the study at 
timepoints specified in Table 4. 
6.4.7. 
Echocardiogram and Multigated Acquisition Scan 
An assessment of LVEF will be performed by ECHO or MUGA scan to assess the cardiac 
function of the subject and to confirm study eligibility. 
6.4.8. 
Electrocardiogram 
A standard 12-lead ECG should be obtained at timepoints indicated in Table 4. 
Electrocardiogram tracings should be labelled with the study number, subject number, date, 
and Investigator’s signature, and kept in the source documents at the study site. 
6.4.9. 
Replication-Competent Lentivirus Testing 
Replication-competent lentivirus testing will be performed on genomic DNA obtained by a 
peripheral blood draw and, if positive, confirmed on PBMC. Details regarding sample 
collection and processing are provided in the JCAR017-BCM-001 laboratory manual. Testing 
for RCL will utilize a polymerase chain reaction based assay. 
Samples for RCL testing will be collected at timepoints indicated in Table 4. If all samples 
collected within the first year after the dose of JCAR017 are negative, subsequent samples 
will be collected and archived. However, if any of the samples are positive, the test will be 


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repeated to confirm the result. If the repeat test is also positive, further analysis of the RCL 
will be undertaken in order to ascertain the nature of the RCL and potential effects. Subjects 
with detectable RCL are expected to continue to have blood samples collected and tested 
until RCL is undetectable. If RCL is detected, further analysis of the RCL will be performed 
and more extensive follow-up measures will be undertaken as appropriate until RCL becomes 
undetectable. Any confirmed positive result from RCL testing will be reported as an SAE 
within 24 hours and as an adverse experience in the form of an Investigational New Drug 
(IND) safety report. In addition, the relevant health authorities will be notified of the detected 
RCL. 
Samples will be archived with appropriate safeguards to ensure long-term stability and an 
efficient system for the prompt linkage and retrieval of the stored samples with the subject’s 
study records and the production lot records. Archived samples will be destroyed as outlined 
in the separate LTFU protocol. 
If a subject develops a secondary malignancy, Celgene will request a sample for detection of 
CAR T sequence. An unscheduled blood draw may also be collected for RCL testing. 
6.4.10. 
Persistent Vector Sequence Monitoring 
Persistence of JCAR017 vector sequence will be monitored at timepoints indicated in 
Table 4. Details regarding sample collection and processing are provided in the JCAR017- 
BCM-001 laboratory manual. The presence of vector sequences will be determined by 
evaluation of blood samples for the JCAR017 transgene by qPCR. If more than 1% of cells in 
test samples collected at the Day 365 visit or later tested positive for vector sequences, the 
pattern of vector integration sites was then to be analyzed. If integration pattern suggests a 
predominant integration site, a repeat analysis will be conducted within 3 months and further 
studies including insertion site analysis will be performed. 
6.4.11. 
Clinical Laboratory Evaluations 
Screening and other laboratory evaluations (see Appendix E) will be performed according to 
Table 4. Additional assessments should be performed between scheduled study visits as 
clinically required in order to diagnose and monitor AEs/SAEs or expected events. Clinical 
management of study subjects will be based on local assessments. 
6.5. 
Efficacy Assessment 
• DLBCL, FL3B: Efficacy response will be assessed according to the 
“Recommendations for Initial Evaluation, Staging, and Response Assessment of 
Hodgkin and non-Hodgkin lymphoma: The Lugano Classification” (Cheson, 
2014) (see Appendix C) based on radiographic tumor assessments. Subjects will 
have radiographic disease assessment by PET and/or CT/MRI scans at 
pretreatment evaluation and approximately 1, 3, 6, 9, 12, 18 and 24 months 
following JCAR017 infusion or until progressive disease or relapse 
− For subjects with secondary CNS involvement: Brain MRI and repeat CSF 
assessments by flow cytometry 
• PCNSL: Efficacy response will be assessed according to the “Report of an 
International Workshop to Standardize Baseline Evaluation and Response Criteria 
for Primary CNS Lymphoma” (Abrey, 2005) at pretreatment evaluation and 
approximately 1, 2, 4, 6, 9, 12, 18 and 24 months following treatment based on the 
following assessments: 


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− Brain MRI 
− CSF assessment (if positive at pre-treatment or suspicion of relapse) 
− PET-CT mandatory at screening to assess for potential systemic involvement. 
Thereafter, PET-CT does not need to be repeated in the absence of systemic 
disease at baseline or suspicion of systemic PD 
6.5.1. 
Pseudoprogression 
If a subject demonstrates early tumor progression (defined as occurring prior to/at 3 months 
after JCAR017 infusion), the Investigator is responsible for evaluating whether the subject is 
experiencing a possible pseudoprogression (ie, tumor flare, which is a local inflammatory 
reaction indicating early tumor response at sites of disease such as lymph nodes; (Cheson, 
2016). 
6.5.2. 
Independent Review Committee 
An independent review committee (IRC) will be established to review radiographic and 
pertinent clinical data (as appropriate) and to determine response and progression status on an 
ongoing basis. The details of the IRC processes and review methods will be described in an 
IRC charter. Clinical management of study subjects will be based upon Investigator’s 
assessment. The findings of the IRC will be considered primarily for analyses of efficacy 
endpoints. 
6.6. 
Pharmacokinetics 
Assessment of JCAR017 PK will be determined by qPCR to detect the JCAR017 transgene 
and by flow cytometry to enumerate the number and immunophenotype of JCAR017 cells. 
Pharmacokinetics by flow cytometry will not be done at Japanese sites. Peripheral blood will 
be collected as indicated in Table 4. 
Detailed information regarding the collection, handling, and shipment of PK assessment 
samples is provided in the JCAR017-BCM-001 laboratory manual. 
6.7. 
Biomarkers, Pharmacodynamics, Pharmacogenomics 
6.7.1. 
Immunogenicity Assessments 
Immune responses to JCAR017 will be evaluated with an anti-therapeutic antibody (ATA) 
assay to detect the presence of serum antibodies that bind to the extracellular region of 
JCAR017. Additional methods, such as ELISpot, may also be used to evaluate cellular 
immune responses to JCAR017 using peripheral blood mononuclear cells (PBMCs). 
Peripheral blood will be collected for these studies at the timepoints indicated in Table 4. 
Detailed information regarding the collection, handling, and shipment of immunogenicity 
assessment samples is provided in the JCAR017-BCM-001 laboratory manual. 
6.7.2. 
Biomarker Assessments 
Exploratory biomarker assessments will include, but are not limited to, immunophenotypic 
and genomic evaluation of JCAR017 and circulating cells in peripheral blood, 
characterization of tumor and tumor microenvironment, and analysis of plasma cytokines. 
Sample specimens will be collected for these studies at the timepoints indicated in Table 4 
and Table 6 for exploratory biomarkers. 


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Table 6: 
Exploratory Biomarkers Sampling 
 
Biomarker Assessment Type 
Sample Type 
Timepoint 
Pharmacokinetics (PK) by flow 
cytometry 
Peripheral blood 
Screening, D1, D4, D8, D11, D15, D22, 
D29, D60, D90, D180, D270, D365, 
D545, D730 
Immunophenotyping (circulating 
T cell subset and JCAR017) 
Peripheral blood 
Screening, leukapheresis (prior), D8, 
D15, D22, D29, D60, D180 
Soluble factors 
Plasma 
Screening, pretreatment evaluation, D1 
(pre-infusion), D4, D8, D11, D15, D22, 
D29 
PBMC isolation 
Peripheral blood 
Screening, D15, D29, D60, D180 
Disease characterization 
Tumor biopsy 
Screening, D15 and at progression 
Abbreviations: D = day; PBMC = peripheral blood mononuclear cells. 
Tumor tissue biopsy will be collected to investigate cellular elements within the tumor and 
the tumor microenvironment for biomarkers related to clinical efficacy and association with 
disease features (eg, cell of origin, cytogenetics). In addition, tumor biopsy specimens will be 
analyzed for expression of various markers. Characterization of the tumor specimen may 
provide insights into the pathways operative in the tumor microenvironment that may 
influence the fate and function of adoptively transferred JCAR017. 
The tumor biopsy will be collected by either tumor excision, incision or multiple core needles 
(4 passages preferred) and processed for formalin fixed paraffin embedding. In addition to 
standard clinical histology, genetic mutation analysis and expression of various markers of 
resistance and efficacy will be performed. 
It is strongly recommended to submit to the central laboratory any archival tumor biopsy 
samples collected prior to study entry or during the study at timepoints other than described 
above for biomarker analysis. 
Peripheral blood and plasma will be collected to evaluate the following: 
• Immunophenotyping will be done to characterize JCAR017 and circulating 
immune cell subsets to identify protein and nucleic acid markers correlated with 
JCAR017 activation, persistence and possible regulation of JCAR017 cells by 
circulating immune cells 
• Soluble factors from plasma will be measured as a marker of immune activation 
and to determine potential correlations between cytokine production, efficacy and 
severity of CRS and neurotoxicity 
• Gene expression profiling (eg, ribonucleic acid-sequencing [RNA-Seq]) and 
various analyses at the nucleotide level may be conducted on JCAR017 cells and 
immune cells in order to identify markers or gene signatures correlating with 
clinical response 
The data collected in these biomarker assessments will be used in aggregate to elucidate 
relationship with CAR T cell function, persistence, molecules present in the tumor/tumor 
microenvironment, and peripheral blood to clinical response and toxicity. 


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Detailed information regarding the collection, handling, and shipment of biomarker samples 
is provided in the JCAR017-BCM-001 laboratory manual. 
6.8. 
Patient-Reported Outcomes 
Patient-reported quality-of-life outcomes will be administered according to Table 4. 
If the subject withdraws from the study prematurely, all attempts should be made to obtain a 
final quality-of-life questionnaire prior to subject discontinuation. EQ-5D-5L and EORTC 
QLQ-C30 and the FACT-LymS will be used to assess the subject’s health as well as physical, 
social, emotional, and functional well-being. 
The questionnaires will be completed by the subjects before any clinical assessments are 
performed at any given visit. If subjects refuse to complete all or any part of a questionnaire, 
this will be documented in the case report form (CRF). Questionnaires should be completed 
in the language most familiar to each subject, and subjects should be given adequate time and 
space to complete the questionnaires. Site personnel should review questionnaires for 
completeness and ask subjects to complete any missing responses. The reasons for any 
missing questionnaires will be documented (eg, subjects too sick to complete questionnaire, 
subject unwilling to complete questionnaire and questionnaire not administered to subject due 
to administrative error). 
Where feasible, patient interviews will be used to capture the experience of JCAR017 therapy 
from a subject perspective. 
6.8.1. 
EORTC QLQ-C30 
The EORTC QLQ-C30 questionnaire will be used as a measure of health-related quality of 
life. The QLQ-C30 is composed of both multi-item scales and single item measures. These 
include five functional scales (physical, role, emotional, cognitive and social), 3 symptom 
scales (fatigue, nausea/vomiting, and pain), a global health status/health-related quality of life 
(HRQoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, 
and financial difficulties). Each of the multi-item scales includes a different set of items – no 
item occurs in more than one scale. 
The QLQ-C30 questionnaire employs a week recall period for all items and a 4-point scale 
for the functional and symptom scales/items with response categories “Not at all”, “A little”, 
“Quite a bit” and “Very much”. The 2 items assessing global health status/HRQoL utilize a 7- 
point scale ranging from 1(“Very Poor”) to 7 (“Excellent”) (Aaronson, 1993) (see 
Appendix I). 
6.8.2. 
EQ-5D-5L 
EQ-5D is a standardized measure of health status developed by the EuroQol Group in order 
to provide a simple, generic measure of health for clinical and economic appraisal. The EQ- 
5D-5L consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ 
VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, 
pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight 
problems, moderate problems, severe problems, extreme problems). 
In 2005, a Task Force was established within the EuroQol Group to investigate methods to 
improve the instrument’s sensitivity and to reduce ceiling effects. After much discussion, the 
Task Force decided that there should be no change in the number of dimensions for a new 
version of EQ-5D. 


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However, previously published studies by EuroQol Group members showed that 
experimental 5-level versions of EQ-5D could significantly increase reliability and sensitivity 
(discriminatory power) while maintaining feasibility and potentially reducing ceiling effects. 
The EQ-5D-5L still consists of 2 pages – the EQ-5D-5L descriptive system (page 1) and the 
EQ Visual Analogue Scale (page 2). The descriptive system comprises the same 5 
dimensions as the EQ-5D-3L (mobility, self-care, usual activities, pain/discomfort, 
anxiety/depression). 
However, each dimension now has 5 levels: no problems, slight problems, moderate 
problems, severe problems, and extreme problems. The respondent is asked to indicate 
his/her health state by ticking (or placing a cross) in the box against the most appropriate 
statement in each of the 5 dimensions. This decision results in a 1-digit number expressing 
the level selected for that dimension. The digits for 5 dimensions can be combined in a 5- 
digit number describing the respondent’s health state. It should be noted that the numerals 1 
to 5 have no arithmetic properties and should not be used as a cardinal score. 
The EuroQol Group had received feedback over the years that respondents sometimes found 
it difficult to draw a line from the box to the scale. It was also cumbersome for administrators 
to record their scores. The EQ-5D-5L now asks respondents to simply ‘mark an X on the 
scale to indicate how your health is TODAY’ and then to ‘write the number you marked on 
the scale in the box below’. 
This should make the task easier for both respondents and users (EuroQol, 1990; Herdman, 
2011) (see Appendix J). 
6.8.3. 
FACT-LymS 
The Functional Assessment of Cancer Treatment-Lymphoma “Additional concerns” subscale 
(FACT-LymS) consists of the FACT-General scale and a 15-item lymphoma-specific 
additional concerns subscale (LYM). This scale addresses symptoms and functional 
limitations that are important to lymphoma patients. Only the LYM subscale will be 
administered in this study. The LYM items are scored on a 0 (“Not at all”) to 4 (“Very 
much”) response scale. Items are aggregated to a single score on a 0-60 scale (see 
Appendix K). 
6.8.4. 
Patient Interviews 
Standardized measures of HRQoL have not been widely used in evaluations of CAR T cell 
therapies and due to the novelty of JCAR017 much has yet to be learned about its impact on 
HRQoL, which may currently be missed by these standard HRQoL measures. For this reason, 
subjects will be invited to be interviewed during the study; the aim being to provide an 
opportunity for subjects to share their experiences of JCAR017 therapy in their own words, 
capturing insights not usually recorded via the established patient-reported outcomes (PRO) 
scales and questionnaires. 
Where feasible, subjects will be requested to participate in a series of interviews over the 2- 
year study period according to Table 7. The interviews will be structured by a discussion 
guide. 
The first interview will last up to one hour and will be conducted in-person or via telephone. 
The remainder of the interviews will be shorter in duration, lasting approximately 30 minutes, 
and may be conducted either over the telephone or in-person. Interviews will be scheduled at 
a time convenient to the subjects. 


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During the interviews, subjects may be asked about: 
• Their experience of B-cell NHL, including symptoms and how the condition 
affects their life 
• Their experience with JCAR017 therapy 
• Their decision to participate in the study 
• Their experiences during the study 
The patient interviews will include a combination of closed and open-ended items, but will 
predominantly provide qualitative data. Any quantitative data will be presented descriptively. 
Robust qualitative methods will be applied to the development of all materials and analysis, 
in line with gold standard PRO practices such as those required by the Food and Drug 
Administration (FDA) for PRO instrument development and industry good research practice 
publications (Patrick, 2011). 


 
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Table 7: 
Table of Events, Patient Interviews 
 
Pretreatment Period 
Treatment Period 
Post-Treatment Period 
Screen- 
ing 
Leuka- 
pheresis 
Pretreat- 
ment 
Evalua- 
tion 
LD 
Chemo- 
therapy 
JCAR017 
Infusion 
Follow-Up 
Study Day 
7 to 14 
days 
before 
leuka- 
pheresis 
Within time 
from 
screening to 
leukapheresis 
Within 7 
days 
before 
LD 
chemo- 
therapy 
Start 5 
to 10 
days 
before 
Day 1 
1 
2 
3 
4 
8 
11 
15 
22 
29 
60 
90 
180 270 365 545 
730 
(EOS) 
or ET 
Visit Window (Days) 
- 
- 
- 
- 
+2 
- 
- 
+1 
±1 
±1 
±2 
±2 
±2 
+14 +14 +35 +35 +35 +35 
+35 
Patient interviewsa for 
subjects enrolled under 
Protocol Amendment 1, 2 
- 
xb 
x 
- 
xc 
- 
- 
- 
- 
- 
- 
- 
x 
x 
x 
x 
x 
x 
x 
x 
Patient interviewsa for 
subjects enrolled under 
Protocol Amendment 3 
- 
xd 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
xe 
- 
xe 
- 
- 
- 
Abbreviations: EOS = end of study; ET = early termination; LD = lymphodepleting. 
a Patient interviews will be performed by an external organization with specialist expertise in conducting patient interviews. 
b Interview is to be performed before the leukapheresis. 
c A window of 72-hours post-JCAR017 infusion is allowed. 
d If missed, interview is to be performed at Pretreatment Evaluation. 
e Interview is to be performed from study visit until 28 days after study visit. 
 
6.9. 
Hospital Resource Utilization 
Hospital resource utilization will be assessed based on the numbers of ICU inpatient days and non-ICU inpatient days in addition to 
outpatient visits. Dates of admission and discharge to the hospital and to the ICU will be collected together with the reasons for the 
hospitalization(s). 
 
 
 
 
 
 
 
 
 
 
 
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7. 
DESCRIPTION OF STUDY TREATMENTS 
7.1. 
Lymphodepleting Chemotherapy 
See Section 1.3.2 for a description of fludarabine and cyclophosphamide. 
7.2. 
Description of Investigational Product 
7.2.1. 
JCAR017 
See Section 1.2.3 for a description of JCAR017. 
See the JCAR017 Product Administration Manual for details of packaging and labeling, product 
request and shipment, product preparation and administration, and product disposal and 
destruction. 
7.3. 
Treatment Administration and Schedule 
7.3.1. 
Lymphodepleting Chemotherapy 
Subjects will be treated with fludarabine IV (30 mg/m2/day for 3 days) and cyclophosphamide 
IV (300 mg/m2/day for 3 days) prior to JCAR017 infusion. Except for Japan, fludarabine and 
cyclophosphamide will be sourced locally by the clinical site. Refer to the most recent package 
inserts for further details on the administration of these agents (Cyclophosphamide, 2017; 
Fludarabine, 2019). 
Lymphodepleting chemotherapy can start 5 to 10 days before JCAR017 infusion and must be 
completed at least 2 days before JCAR017 infusion. If side effects from the LD chemotherapy 
occur, JCAR017 infusion may be delayed for up to 14 days after LD chemotherapy upon 
discussion with Celgene. If the delay is more than 14 days, some of the screening procedures as 
well as LD chemotherapy may need to be repeated. Refer to Section 6.2.1 for the assessments 
that will be performed on each day of LD chemotherapy. 
Serum creatinine will be measured on the first day of LD chemotherapy; LD chemotherapy 
should be withheld if serum creatinine is > 1.5 times the ULN OR calculated creatinine clearance 
(eGFR by Cockcroft-Gault, see Appendix F) or radioisotope glomerular filtration rate (GFR) is ≤ 
30 mL/min. 
The recommended administration is as follows: 
• The IV hydration is 1 L of 0.9% NaCl given at 500 mL/hr starting 2 hours prior to 
cyclophosphamide 
• Fludarabine IV 30 mg/m2 over 30 minutes 
− If CrCl 50 to 70 mL/min: Reduce dose by 20% for each daily dose 
− If CrCl 30 to 49 mL/min: Reduce dose by 40% for each daily dose 
− If CrCl < 30 mL/min: Do not administer fludarabine 
• Cyclophosphamide IV 300 mg/m2 over 60 minutes 


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• Additional 1 L of 0.9% NaCl given at 500 mL/hr 
Antiemetic therapy may be given prior to LD chemotherapy per institutional practice. Mesna 
may be used for subjects with a history of hemorrhagic cystitis per institutional practice. 
7.3.2. 
JCAR017 Premedication 
Subjects should be premedicated with 500 to 650 mg acetaminophen oral (PO) and 25 to 50 mg 
diphenhydramine hydrochloride (PO or IV) 30 to 60 minutes prior to JCAR017 infusion. In case 
the diphenhydramine hydrochloride is not available in a country, it is acceptable to use another 
H1 antihistamine. 
These medications may be repeated every 6 hours as needed based on the Investigator’s 
assessment of symptoms. Premedication with steroids should be avoided. 
7.3.3. 
JCAR017 Preparation and Cell Thawing 
See the JCAR017-BCM-001 Product Administration Manual for details. 
7.3.4. 
JCAR017 Administration 
JCAR017 will be infused at a dose of 100 x 106 JCAR017-positive transfected viable T cells 
(50 × 106 CD8+ CAR+ T cells and 50 × 106 CD4+ CAR+ T cells), on Day 1 (2 to 7 days after 
completion of LD chemotherapy). Each JCAR017 dose consists of CD4+ CAR+ T cells and 
CD8+ CAR+ T cells. The subject must be continuously monitored during IV administration of 
JCAR017. Vital signs (temperature, respiratory rate, heart rate, blood pressure, and SaO2 by 
pulse oximetry) will be measured within 15 minutes prior to the first JCAR017 administration, 
and approximately every 15 minutes thereafter for the first hour, and hourly for the next 2 hours. 
If the subject’s vital signs are not stable 4 hours following the final IV administration, vital signs 
should be monitored as clinically indicated until stable. 
See the JCAR017-BCM-001 Product Administration Manual for complete information. 
7.3.5. 
Protocol Product Deviation Plan 
The JCAR017 Protocol Product Deviation Plan (PPDP) addresses the use of the non-conforming 
investigational product in global clinical trials. The JCAR017 PPDP defines an assessment and 
decision-making process that permits release to the investigator and clinical site of drug product 
that does not meet the specification for certain non-safety related attributes (non-conforming 
product). In this process, the Celgene Medical Monitor and the Primary Investigator at the 
clinical site agree that the health of the subject and the risk/benefit profile is acceptable for the 
subject to receive treatment with the non-conforming investigational product. Development 
Quality Assurance then assesses the recommendation and is ultimately responsible for the drug 
product lot disposition. The JCAR017 PPDP is a standalone document. 
7.3.6. 
Exception Use of Non-conforming Product 
Once a decision is made for the exception use of non-conforming product, country-specific 
requirements will be followed for the release of the non-conforming product to treat a subject 
enrolled in a JCAR017 clinical trial. For example, approval from the local health authorities 
and/or IRBs/ECs will be obtained where required. In the EU, requirements provided in Section 


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11.54 of the EU Guideline on good manufacturing practice specific to advanced therapy 
medicinal products (European Commission, 2017) will be followed. Any subject will need to 
provide consent prior to receiving the non-conforming product. While subjects treated with the 
non-conforming product will be followed as per the Table of Events (Table 4) listed in the 
protocol, their data will be excluded from the primary safety/efficacy evaluable analysis. Their 
data will be analyzed separately. 
Subjects treated with non-conforming product will be replaced for the purposes of study 
enrollment of per protocol evaluable subjects. 
7.3.7. 
Overdose 
Overdose, as defined for this protocol, refers to fludarabine (IV), cyclophosphamide (IV) or 
JCAR017 (IV). On a per-dose basis, an overdose is defined as the following amount over the 
protocol-specified dose of these drug(s) assigned to a given subject, regardless of any associated 
AEs or sequelae: 
• IV: 10% over the protocol-specified dose 
On a schedule or frequency basis, an overdose is defined as anything more frequent than the 
protocol required schedule or frequency. On an infusion rate basis, an overdose is defined as any 
rate faster or slower than the protocol-specified infusion time reflected as infusion time (±50%). 
Complete data about drug administration, including any overdose, regardless of whether the 
overdose was accidental or intentional, should be reported in the CRF (see Section 10 for the 
reporting of AEs associated with overdose). 
7.4. 
Method of Treatment Assignment 
Interactive response technology will be employed to manage cohort assignments. 
7.5. 
Packaging and Labeling 
7.5.1. 
Product Tracking 
The identity of the JCAR017 cell product will be checked and verified at each critical step of cell 
processing as part of the chain of identity. Procedures will be in place to address product tracking 
requirements and will encompass all process steps including collection of the leukapheresis 
product, receipt of the leukapheresis product, JCAR017 manufacturing and testing, in-process 
labeling, and JCAR017 labeling and packaging for shipment. 
7.5.2. 
Product Packaging and Labeling 
The label(s) for the JCAR017 cell product will include, but may not be limited to, Sponsor name, 
address and telephone number, the protocol number, cell product name, dosage form and 
strength (where applicable), amount of JCAR017 cell product per container, lot number, expiry 
date (where applicable), medication identification/kit number, dosing instructions, storage 
conditions, and required caution statements and/or regulatory statements as applicable. 
Additional information may be included on the label as applicable per local regulations 


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These same identifiers are maintained from leukapheresis collection throughout the 
manufacturing process and are used on the final JCAR017 cell product. These unique identifiers 
should be verified per the Chain of Identity procedures listed in the JCAR017 Product 
Administration Manual. 
The final JCAR017 cell product is provided frozen and packaged to the study site per the dosing 
regimen specified in the protocol. 
Prior to the JCAR017 infusion, two trained individuals will verify all unique identifier 
information in the presence of the subject to confirm that the information is correctly matched to 
the subject. 
7.5.3. 
Cell Product Supply and Storage 
Detailed instructions on the storage, handling, and preparation of JCAR017 cell product will be 
provided in the JCAR017 Product Administration Manual. 
7.6. 
Investigational Product Accountability and Disposal 
7.6.1. 
Accountability Procedures 
An inventory must be performed and a product receipt log filled out and signed by the person 
accepting the shipment of JCAR017 cell product. 
7.6.2. 
Drug Disposal and Destruction 
Celgene (or designee) will review with the Investigator and relevant site personnel the process 
for JCAR017 cell product return, disposal, and/or destruction including responsibilities for the 
site versus Celgene (or designee). 
7.7. 
Investigational Product Compliance 
For the IV medication of JCAR017, the administered dosage will be recorded in the source 
documents. The Investigator(s) or designee is responsible for taking an inventory of each 
JCAR017 cell product received and comparing it with the accompanying shipping 
order/packaging slip. The Investigator(s) will verify the accuracy of the information on the 
shipping order/packaging slip. 
At the study site, the JCAR017 cell product will be stored in a locked, safe area to prevent 
unauthorized access and should be stored as directed on the product label. 
An accurate accounting of the dispensing and return of JCAR017 cell product for each study 
subject will be maintained in source documents on an ongoing basis by a member of the study 
site staff. Additionally, the JCAR017 cell product is lost or damaged, this information should be 
documented in the study subject’s CRF and source documents. 
Celgene will instruct the Investigator on the return, disposal, and/or destruction of unused cell 
product. 


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8. 
CONCOMITANT MEDICATIONS AND PROCEDURES 
8.1. 
Permitted Concomitant Medications and Procedures 
Medications taken by the subject at the time of an AE related to protocol-mandated procedures 
will be recorded from informed consent until initiation of LD chemotherapy. All medications 
will be recorded from the time of initiation of LD chemotherapy until 90 days after last dose of 
JCAR017. From 91 days post last dose of either LD chemotherapy or JCAR017 until the EOS 
visit, concomitant medications ongoing at the time of JCAR017 or LD chemotherapy-related 
AEs will be recorded. For subjects receiving lymphodepleting chemotherapy but not JCAR017, 
concomitant medications associated with AEs will be recorded for 30 days following the last 
dose of lymphodepleting chemotherapy. 
Subjects should be discouraged from use of illicit drugs, herbal remedies, self-prescribed drugs, 
tobacco products, or excessive alcohol at any time during the clinical study. 
If necessary, anticancer treatment is allowed for disease control while JCAR017 is being 
manufactured (see Section 6.1.3). 
Due to the large amount of data generated during hospitalizations, a targeted concomitant 
medication collection approach will be utilized for the CRF. Therefore, the following 
medications should NOT be entered on the CRF during inpatient and Intensive Care Unit (ICU) 
stays: 
• IV fluids (with the exception of IV fluids administered for treatment of hypotension 
associated with CRS, which should be recorded) 
• Heparin flushes 
• Stool softeners 
• Vitamins, minerals, health supplements 
• Saline flushes 
• Lotions 
The following treatments should be reported during inpatient and ICU stays: 
• Vasopressors 
• Oxygen use 
• Antibiotics 
• Growth factors 
8.2. 
Prohibited Concomitant Medications and Procedures 
Immunosuppressive medications including, but not limited to systemic corticosteroids at doses 
exceeding 20 mg/day of prednisone or equivalent, methotrexate, azathioprine, and tumor 
necrosis factor alpha (TNF-α) blockers. 
The following medications are prohibited until lack of response, subsequent therapy for 
lymphoma, or 1 year following JCAR017 infusion, whichever comes first: 


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• Steroids: therapeutic doses (> 20 mg/day of prednisone or equivalent) unless used for 
treatment of sCRS. Therapeutic doses may be used in life-threatening situations, for 
other medical conditions when indicated, or after loss of detectable JCAR017 cells. 
Pretreatment containing steroids may be given for necessary medications (eg, IVIG) 
after discussion with Celgene. Premedication with steroids for JCAR017 infusion is 
not allowed. Physiologic replacement dosing of steroids is allowed. Topical steroids, 
inhaled steroids, and intrathecal steroids for CNS relapse prophylaxis are permitted 
The following medications are prohibited during the treatment and follow-up periods unless used 
as an anticancer agent after lack of adequate response to JCAR017 or progression of lymphoma: 
• Donor lymphocyte infusions 
• Immunosuppressive therapies (eg, calcineurin inhibitors, methotrexate or other 
chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive 
antibodies such as anti-TNF, anti-IL-6, or anti-IL-6R), unless needed for treatment of 
GVHD 
• Non-protocol-specified anticancer agents. Lymphocytic cytotoxic chemotherapy may 
be administered as an extraordinary measure to treat AEs of uncontrolled JCAR017 
proliferation, or CRS or neurotoxicity unresponsive to other therapeutic interventions 
• Cetuximab, or other anti-EGFR treatments, unless intended for treatment of 
uncontrolled JCAR017 proliferation 
• Experimental agents 
• Radiation, unless needed for local control of a single tumor lesion in the presence of 
other non-irradiated PET-positive lesions 
8.3. 
Concomitant Medications and Procedures 
Prophylactic treatment/measures are strongly recommended for subjects at risk for tumor lysis 
syndrome (TLS), per institutional or clinical standards. 
Lymphodepleting regimens accompany JCAR017 administration and utilize cyclophosphamide 
and fludarabine. Please refer to the currently approved cyclophosphamide and fludarabine 
phosphate Summary of Product Characteristics (SmPC) (Cyclophosphamide, 2017; Fludarabine, 
2019). 
To minimize the risk of infusion reactions, all subjects should be premedicated with 
acetaminophen and diphenhydramine prior to JCAR017 infusion (see Section 7.3.2). 
Supportive care for the management of CRS is detailed in Appendix M. In some cases, 
tocilizumab, an anti-IL-6R-antibody, may be required to treat toxicities such as severe cytokine 
release syndrome. Please refer to currently approved RoActemra® SmPC (RoActemra®, 2019). 
As per the approved EU SmPCs for CAR T cell therapy, the EMA is expecting a minimum of 4 
doses of tocilizumab to be available prior to infusion for the management of CRS. For CAR T 
site in the EU, the recommendation is to follow the labeled guidance from the EMA. However, 
it is important to understand that the JCAR017 Management Guidelines for Cytokine Release 
Syndrome and Neurotoxicity and the recommended use of tocilizumab is different from the CRS 
management algorithms of the approved CAR Ts. Hence, Celgene requires that all JCAR017 


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global sites (eg, US, EU, Japan) must have at least 2 doses of tocilizumab available prior to 
infusion per a given subject. It is recommended to resupply in case tocilizumab is given. 
The preferred dose to intervene in subjects with sCRS is 8 mg/kg. Other anti-IL-6 antagonist, if 
available in the country concerned, should be considered in the event of sCRS not responding to 
tocilizumab. Dosing of any other anti-IL-6 agent should be per prescribing information. 
The use of red blood cells and platelet transfusions, and/or colony-stimulating factors is 
permitted per institutional or clinical standards. 
The use of prophylactic or empiric anti-infective agents (eg, trimethoprim/sulfamethoxazole for 
pneumocystis pneumonia [PCP] prophylaxis, broad spectrum antibiotics, antifungals, or antiviral 
agents for febrile neutropenia) is permitted per institutional standards. 


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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Overview 
This is a single-arm, multi-cohort, multi-center, Phase 2 study to determine the efficacy and 
safety of JCAR017 in adult subjects with r/r DLBCL or with other advanced B-cell malignancies 
including FL3B and CNS lymphoma. 
Data from all sites will be combined for the final analysis for each cohort. Results will be 
presented using descriptive statistics. 
Efficacy information will be summarized separately per cohort. Safety information will be 
analyzed per cohort and across cohorts. PK information will be combined for all subjects across 
cohorts. 
The data generated from Cohort 2 will complement the data from Study 017006 (PILOT) 
enrolling a similar population in the US. 
9.2. 
Study Population Definitions 
In this study the following analysis populations will be defined for the analysis and presentation 
of the data. 
9.2.1. 
Screened Set 
The Screened set will include all subjects who have signed informed consent. 
9.2.2. 
Enrolled Set 
The Enrolled set will include all subjects who have signed informed consent, who pass all 
eligibility criteria at screening and undergo leukapheresis. 
9.2.3. 
Leukapheresed Set 
The Leukapheresed set will include all subjects who have undergone leukapheresis. 
9.2.4. 
JCAR017-Treated Set 
The JCAR017-treated set will include all subjects who have received JCAR017 cell product. 
9.2.5. 
Efficacy Evaluable Set 
The Efficacy Evaluable set will include all subjects who have received the JCAR017 cell product 
in accordance with drug product release specifications, and who had a baseline assessment and at 
least one post-JCAR017 infusion disease assessment. 
9.2.6. 
qPCR Pharmacokinetic Analysis Set 
The qPCR PK Analysis set includes subjects in the JCAR017-treated set who have both baseline 
and on study PK measurements as assessed by qPCR. 


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9.2.7. 
Flow Cytometry Pharmacokinetic Analysis Set 
The flow cytometry PK Analysis set includes subjects in the JCAR017-treated set who have both 
baseline and on study PK measurements as assessed by flow cytometry. 
9.2.8. 
Patient-Reported Outcome Analysis Set 
The PRO Analysis set will include all subjects who complete their baseline PRO questionnaires 
and have at least one post-baseline measurement in the JCAR017-treated set. 
9.2.9. 
Population Analyses 
Primary efficacy analysis will be based on the JCAR017-treated set. The Enrolled set and 
Efficacy Evaluable set will be used for supportive analyses when applicable. Safety analysis will 
be based on the JCAR017-treated set. The PK analysis will be based on the PK analysis set. 
Patient-reported outcomes will be analyzed based on the PRO Analysis set. 
9.3. 
Sample Size and Power Considerations 
Sample size and power were calculated using EAST® Version 6.4 software system. 
9.3.1. 
Cohort 1 
A sample size of 34 subjects treated with JCAR017 provides at least 90% power to reject the null 
hypothesis of response rate less than 40% assuming the target response rate of 70% using an 
exact binomial test with an overall two-sided significance level of 0.05 considering a formal 
interim analysis with the first 10 subjects treated with JCAR017 being followed for at least 3 
months after JCAR017 infusion to test the superiority of JCAR017. 
An interpolated spending function will be used as efficacy boundary for the interim analysis with 
a significance level of 0.01. The significance level for efficacy for the interim and primary 
analyses will be 0.01 and 0.017 (both one-sided), respectively. The calculation was performed 
using EAST 6.4 (Cytel Inc.). 
The primary analysis for Cohort 1 is planned after at least 34 subjects have been treated with 
JCAR017 and the last subject has been followed for at least 6 months or until death, progressive 
disease, or withdrawal from study. 
9.3.2. 
Cohort 2 
Approximately 28 subjects will be treated with JCAR017 in Cohort 2. A sample size estimate of 
28 subjects treated with JCAR017 would provide at least 80% power to reject the null hypothesis 
of response rate less than 40% assuming the target response rate of 70% using an exact binomial 
test with two-sided significance level 0.05. 
The original null hypothesis had been defined based on a preliminary estimate from the literature 
for 2L populations. A retrospective patient Real-World data cohort will be used as a more 
comparable external/synthetic control to provide the reference rate for the null hypothesis testing 
of ORR ≤ p0% in the primary analysis. Generation of the external control will be described in 
the Real-World Evidence (RWE) Study CA082-014 Statistical Analysis Plan (SAP). The 
primary analysis for Cohort 2 is planned after approximately 28 subjects have been treated with 


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JCAR017 and have been followed for at least 6 months after first response (either CR or PR) or 
until death, progressive disease, or withdrawal from study. 
9.3.3. 
Cohort 3 (Japan only) 
At least 10 subjects treated with JCAR017 will be enrolled to evaluate preliminary efficacy and 
safety. 
In Japan, analysis will be conducted by combining Cohorts 1, 2 and 3. The primary efficacy 
analysis will be performed after at least 10 Japanese subjects in Cohort 3 have been treated with 
JCAR017 and have been followed for at least 3 months or until death, progressive disease, or 
withdrawal from study, and at the time when the number of subjects, who are eligible for the 
Efficacy Evaluable Set, has reached at least 34 subjects when combining Cohorts 1, 2 and 3. The 
primary efficacy analysis and safety analysis will be based on the JCAR017-Treated Set. 
The primary efficacy endpoint is ORR. A sample size of 34 subjects provides at least 90% power 
to reject the null hypothesis of a response rate less than 40% assuming a target response rate of 
70% with a one-sided significance level of 0.025 using an exact binomial test. Hence, we can 
formally test for statistical significance of the results with at least 34 subjects. 
Other efficacy endpoints such as complete response rate, event-free survival, progression-free 
survival, overall survival and duration of response will also be analyzed for these subjects. 
Another objective will be to observe whether there is a consistent trend in the efficacy results for 
the at least 10 Japanese subjects in Cohort 3 (Japan only) compared to the efficacy results in the 
subjects in Cohort 1 and 2. 
With regards to safety, the type, frequency, severity, and causality of AEs, including SAEs and 
laboratory abnormalities, will be reported for these subjects. 
9.3.4. 
Cohort 7 
Cohort 7 is for subjects intended to be treated as outpatients. Subjects will be considered 
outpatients if they leave the clinic or are discharged from the hospital on the day of JCAR017 
infusion. 
This cohort is designed for estimation of incidence of safety events and does not include formal 
hypothesis testing or adjustment for multiplicity. For any individual incidence rate (eg, AEs), 24 
subjects would provide a precision of ± 20.9% to estimate each endpoint assuming a CI of 95%. 
This is based on an event rate of 50% using the exact Clopper-Pearson method. 
An analysis will be conducted when all treated subjects have been followed for at least 6 months 
after first response. In the Juno Study 017001, treatment with JCAR017 in subjects with r/r 
aggressive B-cell NHL resulted in observed incidence rates for Grade ≥ 3 CRS or NT, infections, 
and prolonged cytopenias of 12%, 9%, and 38%, respectively (data on file). If similar rates are 
observed in this study, this would provide sufficient precision for meaningful interpretation of 
the observed rates. Example rates and associated 95% CI are given in Table 8. 


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Table 8: 
Example Rates (± 95% Confidence Intervals) 
 
Rate 
Sample Size 
Expected Count 
Lower 95% CI* 
Upper 95% CI* 
70% 
24 
17 
48.9% 
87.4% 
50% 
24 
12 
29.1% 
70.9% 
38% 
24 
9 
18.8% 
59.4% 
12% 
24 
3 
2.7% 
32.4% 
8% 
24 
2 
1% 
27% 
Abbreviation: CI = Confidence Interval. 
* Based on exact Clopper-Pearson method. 
 
9.3.5. 
Gated Cohorts 
Cohorts 4 and 5 may be opened at Celgene’s discretion (see Section 3.1): 
• Cohort 4: A target of 10 subjects for which JCAR017 has been manufactured will be 
enrolled to evaluate preliminary efficacy and safety 
• Cohort 5: A target of 10 subjects treated with JCAR017 will be enrolled to evaluate 
preliminary efficacy and safety 
• Cohort 6 (REMOVED) 
9.4. 
Background and Demographic Characteristics 
Subject’s age, height, weight, and baseline characteristics will be summarized using descriptive 
statistics, while sex, race and other categorical variables will be provided using frequency 
tabulations for both JCAR017-treated set and Enrolled set for each cohort. Medical history data 
will be summarized using frequency tabulations by Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class (SOC) and preferred term (PT) for both the JCAR017-treated set 
and Enrolled set for each cohort. 
9.5. 
Subject Disposition 
Summaries of subject disposition will be provided for both JCAR017-treated set and Enrolled 
set. The number and percentage of subjects who are eligible for study treatment but not able to 
successfully generate a JCAR017 cell product, along with the reason(s) for manufacturing 
failure, will be summarized per cohort. 
9.6. 
Efficacy Analysis 
9.6.1. 
General Consideration 
The primary efficacy analysis will be based on the JCAR017-treated set. The Leukapheresed set, 
Enrolled set and Efficacy Evaluable set will be used as supportive analysis when applicable. 
For binary endpoints, such as ORR, the frequency distribution (n, %) will be provided. The point 
estimate together with two-sided exact 95% CI will be provided. 


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For time-to-event endpoints such as EFS, PFS and OS, the Kaplan-Meier product limit method 
will be used to estimate the survivorship function. Event rates at specific timepoints will be 
estimated from the Kaplan-Meier curves. Medians together with two-sided 95% CI will be 
calculated. 
9.6.2. 
Primary Endpoint 
The primary efficacy endpoint for Cohorts 1, 2, 3, 4 and 5 is ORR determined by an IRC 
(Cohorts 1, 2 and 3) or by Investigator assessment (Cohorts 4, and 5) after JCAR017 infusion. 
For subjects with NHL (including subjects with secondary CNS involvement) the ORR is 
defined as the proportion of subjects with a best overall response (BOR) of either CR or PR from 
JCAR017 infusion until disease progression, end of study, the start of another anticancer therapy, 
or HSCT. For subjects with PCNSL the ORR is defined as the proportion of subjects with BOR 
of either CR, complete response unconfirmed (Cru) or PR from JCAR017 infusion until disease 
progression, end of study, the start of another anticancer therapy, or HSCT. 
Subjects with unknown or missing response will be included in the analysis counted as non- 
responders (JCAR017-treated set, Leukapheresed set, and Enrolled set). 
Of note, the primary endpoint for Cohort 7 is safety (type, frequency, and severity of all AEs, 
including SAEs and laboratory abnormalities). 
An exact binomial test with 1-sided significance level 0.025 will be used for hypothesis testing 
of ORR. The ORR will be calculated along with the two-sided 95% exact Clopper-Pearson CI. 
9.6.3. 
Secondary Efficacy Endpoints 
Secondary endpoints analyses will be performed to further assess the efficacy of JCAR017. 
Complete Response Rate 
Complete response rate is defined as percentage of subjects achieving a BOR of CR/CRu 
following JCAR017 infusion until disease progression, end of study, the start of another 
anticancer therapy, or HSCT. 
Subjects with unknown or missing response will be included in the analysis counted as non- 
responder (JCAR017-treated set, Leukapheresed set, and Enrolled set). 
Event-free Survival 
Event-free survival is defined as the interval from the date of JCAR017 infusion to the earliest of 
the following events: death from any cause, progressive disease, or starting a new anticancer 
therapy. 
In case a subject does not have an EFS event prior to data cutoff date, EFS will be censored at 
the date of the last adequate disease assessment. 
Progression-free Survival 
Progression-free survival is defined as the interval from the date of JCAR017 infusion to 
progressive disease or death due to any cause, whichever occurs first. 


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Subjects who did not experience progressive disease and who did not die before the data cutoff 
date will be censored at the time of the last visit with adequate response assessment when the 
subjects were known not to have progressed. 
Overall Survival 
Overall survival is defined as the interval from the date of JCAR017 infusion to the date of death 
due to any reason. 
Data from surviving subjects will be censored at the last time that the subject is known to be 
alive. 
Duration of Response 
Duration of response is defined as the interval from the first documentation of response to 
progressive disease or death from any cause, whichever occurs first. Duration of response will be 
evaluated for subjects who achieve a response. 
Subjects who did not experience progressive disease and who did not die before the data cutoff 
date will be censored at the time of the last visit with adequate response assessment when the 
subjects were known not to have progressed. 
Pharmacokinetics 
Maximum concentration, time to peak concentration, area under the curve, and persistence of 
JCAR017 will be analyzed based on the PK analysis sets for qPCR and flow cytometry. 
Health-Related Quality of Life 
Patient-reported outcomes as measured by EORTC QLQ-C30, EQ-5D-5L and the FACT-LymS 
will be analyzed based on the PRO analysis set. 
Overall Response Rate 
Secondary efficacy endpoints for Cohort 7 will also include ORR defined as the proportion of 
subjects with a BOR of either CR or PR from JCAR017 infusion until disease progression, end 
of study, the start of another anticancer therapy, or HSCT. 
9.6.4. 
Subgroup Analyses 
Efficacy subgroup analyses will be performed on the following variables: 
• Age: < 40, ≥ 40 to < 65, ≥ 65 years at screening (additional age categories per cohorts 
are defined in the SAP) 
• Performance status: ECOG 0 versus 1 versus 2 
• Sex: male versus female 
• Ethnicity: Hispanic or Latino versus not Hispanic or Latino 
• Race: white versus other races 
• Prior hematopoietic stem cell transplantation status: yes versus no 
• Prior response status: The status is refractory if a subject achieved less than a CR to 
last prior therapy; otherwise the status is relapsed 


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− Refractory versus relapsed 
− Refractory or relapsed disease < 12 months (defined as a CR lasting no more than 
12 months) versus relapsed ≥ 12 months to first-line therapy (for Cohort 2) 
• Prior chemotherapy response status: chemorefractory versus chemosensitive to last 
therapy. The status is chemorefractory if a subject achieved stable disease or PD to 
last chemotherapy-containing regimen or relapsed < 12 months after autologous stem 
cell transplantation; otherwise the status is chemosensitive 
• CNS disease status: known as CNS disease versus no known CNS disease at 
screening 
• Cell of origin: ABC versus GCB 
• Molecular subtype: HGBL versus DLBCL without MYC and BCL2 and/or BCL6 
rearrangements 
Subgroup analyses will only be performed if there are enough subjects in each subgroup. Some 
grouping of classes will be considered if there are too few subjects in some subgroups. Other 
subgroup analyses may be performed if deemed appropriate, as described in the SAP. 
9.7. 
Safety Analysis 
Safety analysis including treatment-emergent adverse events (TEAE) and laboratory findings 
will be based on JCAR017-treated set aggregated for all cohorts as well as separately for each 
cohort. 
Treatment-emergent adverse events ≥ Grade 3 in subjects infused with JCAR017 in a clinical 
trial setting include neurologic toxicities, such as encephalopathy, hypotension, cytokine release 
syndrome, febrile neutropenia, and hypoxia. These events will be carefully monitored during 
JCAR017 infusion and during follow-up. The following safety assessments will also be 
monitored: 
• The timing and length of inpatient hospitalization 
• Physical examination 
• MMSE and ICE score (if performed) 
• Laboratory evaluations to monitor closely for neurologic changes, CRS, and fever 
• Expected cytopenia and potential infections attributable to the LD chemotherapy 
9.7.1. 
Adverse Events 
• Adverse events will be coded using MedDRA SOC and PT 
• The severity of each adverse event will be graded by the Investigator using CTCAE 
Version 4.03, unless otherwise specified in the protocol. If CTCAE criteria do not 
exist for a given event, the Investigator should use one of the following: Grade 1 
(mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 
(fatal) to describe the maximum intensity of the adverse event 


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• Related AEs are those for which the Investigator selects “Related” to JCAR017 or LD 
therapy on the AE CRF. Relatedness will always default to the Investigator’s choice, 
not that of the Medical Monitor 
• Adverse events will be identified and captured as SAEs if they meet the definition for 
SAE 
9.7.2. 
Definition of Treatment-emergent Adverse Event 
A JCAR017 TEAE is defined as below: 
• Any AE that occurs from start of JCAR017 infusion and up to 90 days after JCAR017 
infusion 
9.7.3. 
Summary of Adverse Events 
All AEs will be listed. The focus of AE summarization will be on JCAR017 TEAEs. 
Adverse event summaries will provide the number and percentage of subjects with TEAEs by 
SOC and PT, based on the JCAR017-treated set as follows (a brief high-level summary will also 
be provided): 
• All AEs 
• All AEs by severity grade 
• Grade ≥ 3 AEs 
• Grade 5 AEs 
• All SAEs 
• All JCAR017-related AEs 
• JCAR017-related Grade ≥ 3 AEs 
• JCAR017-related Grade 5 AEs 
• All JCAR017-related SAEs 
• LD chemotherapy-related AEs 
• All AEs occurring after 90 days following the infusion of JCAR017 
• All AEs recorded between signing informed consent and the infusion of JCAR017 
Multiple occurrence of the same events will be counted only once per subject in each summary. 
Adverse events will be summarized and listed first by SOC in descending order of incidence and 
then by PT (within each SOC), also in descending order of incidence. In summaries by severity 
grade, the most severe grade will be used for those AEs that occur more than once for an 
individual subject during the study. 
In addition to the above summary tables, all TEAEs and SAEs will be summarized by SOC only 
and by PT only in order of descending incidence. 


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9.8. 
Laboratory Evaluations 
The focus of the laboratory data summarization will be on the JCAR017 treatment-emergent 
laboratory abnormalities using the JCAR017-treated set. JCAR017 treatment-emergent 
laboratory abnormalities are defined as an abnormality that, compared to baseline, worsens by at 
least one grade after JCAR017 infusion and up to 90 days after JCAR017 infusion. The baseline 
value is defined as the last available recorded value on or prior to the date of JCAR017 infusion. 
All laboratory data will be listed with a variable indicating whether the event is treatment- 
emergent. 
9.8.1. 
Numeric Laboratory Results 
Summaries of laboratory data will be based on observed data and will be reported using standard 
international units. Baseline, raw values, and changes from baseline will be summarized using 
descriptive statistics for each laboratory test specified in the study protocol. 
Median (Q1, Q3) values for each laboratory parameter will be plotted over time using a box plot. 
Mean ± SE of the observed values and changes from baseline for each laboratory parameter will 
be plotted over time using line plots. 
9.8.2. 
Graded Laboratory Values 
Applicable hematological and serum biochemistry laboratory data will be programmatically 
graded according to CTCAE, Version 4.03 severity grade: mild (Grade 1), moderate (Grade 2), 
severe (Grade 3), or life threatening (Grade 4). Grade 0 includes all non-missing values that do 
not meet criteria for an abnormality of at least Grade 1. Some laboratory tests have criteria for 
both increased and decreased levels; analyses for each direction (ie, increased, decreased) will be 
presented separately. 
9.8.3. 
Summaries of Laboratory Abnormalities 
All laboratory data will be listed. The focus of laboratory data summarization will be on 
JCAR017 treatment-emergent laboratory abnormalities. Summaries (number and percentage of 
subjects) of baseline, post-baseline at each visit, and worst post-baseline treatment-emergent 
laboratory abnormalities will be provided. Subjects will be categorized according to the most 
severe abnormality grade. All summaries of laboratory abnormalities will be based on the 
JCAR017-treated set. 
Shift tables will be presented by showing the change in CTCAE severity grade from baseline to 
each post-baseline visit and to the maximum post-baseline grade. For parameters for which a 
CTCAE severity scale does not exist, shift tables will be presented showing change in results 
from the baseline value (low, normal, and high) to each post-baseline visit and to the worst post- 
baseline value (low, normal, and high). 
9.9. 
Other Topics 
9.9.1. 
Data Safety Monitoring Board 
An independent DSMB will review cumulative study data over the course of the study to 
evaluate safety, protocol conduct, and scientific validity and integrity of the trial. The DSMB, 


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composed of a statistician and select physicians with experience in hematology/oncology and/or 
T cell therapy, will be assembled under a dedicated charter specifically developed for safety 
oversight of the study. DSMB members will not be actively involved in the study design, 
conduct, or subject accrual and must not have financial, proprietary, professional, or other 
interests that may affect impartial, independent decision making. 
The DSMB will be convened prior to enrollment of the first subject on the protocol and will 
meet approximately twice a year throughout the trial and as needed to address any safety issues 
that may arise. Subject safety will be evaluated as specified in the Data Safety and Monitoring 
Plan (DSMP) or DSMB charter. The DSMB will provide advice to Celgene as outlined in the 
DSMB charter. The effectiveness of the risk mitigation plan will be reviewed by the DSMB at 
each meeting. After each DSMB meeting, a statement summarizing the outcome of the review 
will be provided to Celgene. If the DSMB recommends continuing the study, no details from the 
review will be revealed. Celgene will provide this statement from the DSMB review to the study 
Investigators for submission to the site’s IRB/EC within 10 working days after receipt of the 
statement. 
9.9.2. 
Scientific Steering Committee 
The conduct of this trial will be overseen by a scientific steering committee (SSC), presided over 
by the coordinating Principal Investigator and if possible the representative Regional 
Investigators from countries participating in this study. The SSC will serve in an advisory 
capacity to the Sponsor. Operational details for the SSC will be detailed in a separate SSC 
charter. 
Note: The SSC is separate from the DSMB. 
9.9.3. 
Exploratory Analysis 
The PK by flow cytometry, pharmacodynamic (Pd) and biomarker analyses as well as the 
health technology assessment analyses will be specified exploratory analyses. The exploratory 
endpoints of the study are listed in Section 2. Detailed information regarding the collection, 
handling, and shipment of biomarker samples is provided in the JCAR017-BCM-001 laboratory 
manual. Further details of the exploratory analyses are provided in the statistical analysis plan. 
Planned exploratory analyses will include: 
• Characterization of the PK profile of JCAR017 as assessed by flow cytometry to 
enumerate and immunophenotype JCAR017 cells 
• Pharmacodynamic biomarker effects of JCAR017 by assessment of B-cell aplasia, 
immunoglobulins, soluble biomarkers and markers of inflammation (CRP and 
ferritin) 
• Flow cytometry immunophenotyping of JCAR017 cells and resident immune cells in 
the blood 
• Cellular and genomic profiling of tumor biopsy samples to investigate the tumor and 
tumor microenvironment for mechanisms of response and relapse 


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• To characterize the prevalence and incidence of humoral immune responses to 
JCAR017. Cellular immunogenicity may also be evaluated by testing PBMC for the 
presence of anti-JCAR017 cytotoxic T cell 
• Replication-competent lentivirus safety testing will be performed on DNA obtained 
from peripheral blood, the presence of viral vector envelope sequences will be 
assessed using a qPCR based assessment 
• Safety: The effect of treatments directed at sCRS and neurotoxicity on duration and 
severity of sCRS and neurotoxicity 
• Hospital resource utilization: Number of inpatient days, ICU days, and outpatient 
visits 
• Subject experience on JCAR017: Qualitative data obtained from completion of 
patient interviews 


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10. 
ADVERSE EVENTS 
10.1. 
Monitoring, Recording and Reporting of Adverse Events 
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen 
in a subject during the course of a study. It may be a new intercurrent illness, a worsening 
concomitant illness, an injury, or any concomitant impairment of the subject’s health, including 
laboratory test values (as specified by the criteria in Section 10.3), regardless of etiology. Any 
worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre- 
existing condition) should be considered an AE. 
Abuse, withdrawal, sensitivity or toxicity to an investigational product (IP) should be reported as 
an AE. Overdose, accidental or intentional, whether or not it is associated with an AE should be 
reported on the overdose CRF (see Section 7.3.7 for the definition of overdose). Any sequela of 
an accidental or intentional overdose of an investigational product should be reported as an AE 
on the AE CRF. If the sequela of an overdose is an SAE, then the sequela must be reported on an 
SAE report form and on the AE CRF. The overdose resulting in the SAE should be identified as 
the cause of the event on the SAE report form and CRF but should not be reported as an SAE 
itself. 
In the event of overdose, the subject should be monitored as appropriate and should receive 
supportive measures as necessary. There is no known specific antidote for JCAR017, fludarabine 
or cyclophosphamide overdose. Actual treatment should depend on the severity of the clinical 
situation and the judgment and experience of the treating physician. 
All subjects will be monitored for AEs during the study. Assessments may include monitoring of 
any or all of the following parameters: the subject’s clinical symptoms, laboratory, pathological, 
radiological or surgical findings, physical examination findings, or findings from other tests 
and/or procedures. 
Adverse events must be recorded as shown in Table 9. If they meet the seriousness criteria, they 
will be reported to Drug Safety as provided in Section 10.5. 


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Table 9: 
Recording Periods for Adverse Events 
 
Start 
End 
Required Recording 
Signing of 
informed 
consent 
Start of LD 
chemotherapy 
Only AEs related to any study procedure, and any toxicity 
change to ongoing AEs will be recorded in the CRF as a 
separate AE record 
Conditions unrelated to study procedures should be reported in 
the medical history CRF 
Start of LD 
chemotherapy 
Day 90, after 
JCAR017 infusion 
All AEs, irrespective of causality, and any toxicity change to 
ongoing AEs will be recorded in the CRF as a separate AE 
record 
Day 91, after 
JCAR017 
infusion 
End of study 
Only AEs related to any study procedure or JCAR017 will be 
collected; changes in toxicity grade will be recorded as a single 
event with the highest toxicity grade experienced at any time 
during the event recorded 
Start of LD 
chemotherapy 
End of Study 
The following clinical conditions should be reported as SAEs, 
regardless of relatedness to JCAR017: 
• 
Second Primary Malignancies 
• 
New onset or exacerbation of pre-existing neurologic 
disorder 
• 
New onset of rheumatologic disorder or other autoimmune 
disorder 
• 
New onset of hematologic disorder 
Rare and unexpected disorder with an unknown etiology (eg, 
Guillain Barre, Stevens Johnsons Syndrome 
If a subject receives lymphodepleting therapy but not JCAR017, all AE/SAEs should be 
recorded/reported for 30 days following the last dose of lymphodepleting chemotherapy. 
Serious Adverse Events made known to the Investigator at any time thereafter that are suspected 
of being related to IP and/or to any study procedure will be recorded as well. Documentation 
must be supported by an entry in the subject’s source document. 
A diagnosis or syndrome should be recorded on the AE page of the CRF rather than the 
individual signs or symptoms of the diagnosis or syndrome. In addition to recording CRS and 
neurotoxicity as a diagnosis, the signs and symptoms of CRS and neurotoxicity will be recorded 
on separate CRFs. Any medical condition already present prior to first LD chemotherapy should 
not be reported as an AE unless the medical condition is related to any study procedure and 
increases in severity. In this case, it should be reported as an AE and indicated as a worsening 
event. 
Inpatient or ICU stays, while anticipated, are not scheduled protocol-defined visits. In addition, 
inpatient or ICU admissions can generate large amounts of clinical data (eg, multiple 
concomitant medications, frequent concomitant medication dose changes, laboratory values, and 
vital sign assessments). Therefore, targeted collection of data from inpatient or ICU stays, as 
well as a separate CRF for detailing specific adverse events of special interest (AESI; ie, signs 


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and symptoms of CRS and neurotoxicity), will be utilized for the purpose of adequately 
describing the expected risks of JCAR017 and the recommendations for managing these risks. 
Adverse Events and SAEs will be recorded on the AE page of the CRF and in the subject’s 
source documents. All SAEs meeting the criteria described in Table 9 must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method, using the SAE Report Form, or approved equivalent form. 
10.2. 
Evaluation of Adverse Events 
A qualified Investigator will evaluate all adverse events as to: 
10.2.1. 
Seriousness 
An SAE is defined as any AE occurring at any dose that: 
• Results in death; 
• Is life-threatening (ie, in the opinion of the Investigator, the subject is at immediate 
risk of death from the AE); 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization is defined as an inpatient admission, regardless of length of stay). 
• Results in persistent or significant disability/incapacity (a substantial disruption of the 
subject’s ability to conduct normal life functions); 
• Is a congenital anomaly/birth defect; 
• Constitutes an important medical event; 
Important medical events are defined as those occurrences that may not be 
immediately life-threatening or result in death, hospitalization, or disability, but may 
jeopardize the subject or require medical or surgical intervention to prevent one of the 
other outcomes listed above. Medical and scientific judgment should be exercised in 
deciding whether such an AE should be considered serious. 
Events not considered to be SAEs are hospitalizations for: 
• A standard procedure for protocol therapy administration. However, hospitalization 
or prolonged hospitalization for a complication of therapy administration will be 
reported as an SAE 
• Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition 
• The administration of blood or platelet transfusion as routine treatment of studied 
indication. However, hospitalization or prolonged hospitalization for a complication 
of such transfusion remains a reportable SAE 
• A procedure for protocol/disease-related investigations (eg, surgery, scans, 
endoscopy, sampling for laboratory tests, bone marrow sampling). However, 
hospitalization or prolonged hospitalization for a complication of such procedures 
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• Hospitalization or prolongation of hospitalization for technical, practical, or social 
reasons, in absence of an AE 
• A procedure that is planned (ie, planned prior to start of treatment on study); must be 
documented in the source document and the CRF. Hospitalization or prolonged 
hospitalization for a complication remains a reportable SAE 
• An elective treatment of or an elective procedure for a pre-existing condition, 
unrelated to the studied indication, that has not worsened from baseline 
• Emergency outpatient treatment or observation that does not result in admission, 
unless fulfilling other seriousness criteria above 
If an AE is considered serious, both the AE page/screen of the CRF and the SAE Report Form 
must be completed. 
For each SAE, the Investigator will provide information on severity, start and stop dates, 
relationship to LD chemotherapy and/or JCAR017, action taken regarding LD chemotherapy 
and/or JCAR017, and outcome. 
10.2.2. 
Severity and Intensity 
For both AEs and SAEs, the Investigator must assess the severity/intensity of the event. 
The severity/intensity of AEs will be graded based upon the subject’s symptoms according to the 
Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03); 
Adverse Events that are not defined in the CTCAE should be evaluated for severity/intensity 
according to the following scale: 
• Grade 1 = Mild – transient or mild discomfort; no limitation in activity; no medical 
intervention/therapy required 
• Grade 2 = Moderate – mild to moderate limitation in activity, some assistance may be 
needed; no or minimal medical intervention/therapy required 
• Grade 3 = Severe – marked limitation in activity, some assistance usually required; 
medical intervention/therapy required, hospitalization is possible 
• Grade 4 = Life-threatening – extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, hospitalization or hospice 
care probable 
• Grade 5 = Death – the event results in death 
The term “severe” is often used to describe the intensity of a specific event (as in mild, moderate 
or severe myocardial infarction); the event itself, however, may be of relatively minor medical 
significance (such as severe headache). This criterion is not the same as “serious” which is 
based on subject/event outcome or action criteria associated with events that pose a threat to a 
subject’s life or functioning. 
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10.2.3. 
Causality 
The Investigator must determine the relationship between the administration of LD 
chemotherapy and JCAR017 and the occurrence of an AE/SAE as Not Suspected or Suspected as 
defined below: 
• Not suspected:A causal relationship of the adverse event to either LD chemotherapy 
or JCAR017 administration is unlikely or remote, or other medications, therapeutic 
interventions, or underlying conditions provide a sufficient explanation for the 
observed event 
• Suspected: There is a reasonable possibility that the administration of LD 
chemotherapy or JCAR017 caused the adverse event. ‘Reasonable possibility’ means 
there is evidence to suggest a causal relationship between the LD chemotherapy or 
JCAR017 and the adverse event 
Causality should be assessed and provided for every AE/SAE based on currently available 
information. Causality is to be reassessed and provided as additional information becomes 
available. 
If an event is assessed as suspected of being related to a comparator, ancillary or additional LD 
chemotherapy or JCAR017 that has not been manufactured or provided by Celgene, please 
provide the name of the manufacturer when reporting the event. 
10.2.4. 
Duration 
For both AEs and SAEs, the Investigator will provide a record of the start and stop dates of the 
event. 
10.2.5. 
Action Taken 
The Investigator will report the action taken with investigational products as a result of an AE or 
SAE, as applicable (eg, discontinuation, interruption, or dose reduction of investigational 
products, as appropriate) and report if concomitant and/or additional treatments were given for 
the event. 
10.2.6. 
Outcome 
The Investigator will report the outcome of the event for both AEs and SAEs. 
Serious adverse events will be followed until they return to baseline, the event stabilizes or is no 
longer considered clinically significant by the Investigator; the subject dies or withdraws 
consent; or study closure. 
10.3. 
Abnormal Laboratory Values 
An abnormal laboratory value is considered to be an AE if the abnormality: 
• Results in discontinuation from the study; 
• Requires treatment, modification/interruption of LD chemotherapy or JCAR017 cell 
product dose, or any other therapeutic intervention (including transfusions or growth 
factors); or 


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• Is judged to be of significant clinical importance, eg, one that indicates a new disease 
process and/or organ toxicity, or is an exacerbation or worsening of an existing 
condition. 
Regardless of severity grade, only laboratory abnormalities that fulfill a seriousness criterion 
need to be documented as a serious adverse event. 
If a laboratory abnormality is one component of a diagnosis or syndrome, then only the diagnosis 
or syndrome should be recorded on the AE page/screen of the CRF. If the abnormality was not a 
part of a diagnosis or syndrome, then the laboratory abnormality should be recorded as the AE. If 
possible, the laboratory abnormality should be recorded as a medical term and not simply as an 
abnormal laboratory result (eg, record thrombocytopenia rather than decreased platelets). 
10.4. 
Pregnancy 
All pregnancies and suspected pregnancies (including elevated β-hCG or positive pregnancy test 
in a female subject of childbearing potential regardless of disease state) occurring any time after 
receipt of LD chemotherapy or infusion of JCAR017, in either a female subject of childbearing 
potential or a partner of childbearing potential of a male subject are immediately reportable 
events. The pregnancy, suspected pregnancy, or positive pregnancy test must be reported to 
Celgene Drug Safety immediately by email, phone or facsimile, or other appropriate method, 
using the Pregnancy Initial Report Form, or approved equivalent form. 
10.4.1. 
Females of Childbearing Potential 
The Investigator will follow the female subject until completion of the pregnancy and afterwards 
up to 1 year of the newborn baby, and must notify Celgene Drug Safety immediately about the 
outcome of the pregnancy (either normal or abnormal outcome) using the Pregnancy Follow-up 
Report Form, or approved equivalent form. 
If the outcome of the pregnancy was abnormal (eg, spontaneous abortion), the Investigator 
should report the abnormal outcome as an AE. If the abnormal outcome meets any of the serious 
criteria, it must be reported as an SAE to Celgene Drug Safety by facsimile, or other appropriate 
method, within 24 hours of the Investigator’s knowledge of the event using the SAE Report 
Form, or approved equivalent form. 
All neonatal deaths that occur within 28 days of birth should be reported, without regard to 
causality, as SAEs. In addition, any infant death after 28 days that the Investigator suspects is 
related to the in utero exposure to the LD chemotherapy or JCAR017 should also be reported to 
Celgene Drug Safety by facsimile, or other appropriate method, within 24 hours of the 
Investigator’s knowledge of the event using the SAE Report Form, or approved equivalent form. 
10.4.2. 
Male Subjects 
If a female partner of a male subject who has received LD chemotherapy and/or JCAR017 
becomes pregnant, the male subject should notify the Investigator, and the pregnant female 
partner should be advised to call their healthcare provider immediately. The pregnant partner will 
be asked for consent (if permitted by local regulations) for follow-up by the Investigator until 
completion of the pregnancy and afterwards up to 1 year of the newborn baby. 


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10.5. 
Reporting of Serious Adverse Events 
Any AE that meets any criterion for an SAE requires the completion of an SAE Report Form in 
addition to being recorded on the AE page/screen of the CRF. All SAEs must be reported to 
Celgene Drug Safety within 24 hours of the Investigator’s knowledge of the event by facsimile, 
or other appropriate method (eg, via email), using the SAE Report Form, or approved equivalent 
form. This instruction pertains to initial SAE reports as well as any follow-up reports. 
The Investigator is required to ensure that the data on these forms is accurate and consistent. 
This requirement applies to all SAEs (regardless of relationship to LD chemotherapy or 
JCAR017) recorded in the CRF as described in Section 10.1. 
The SAE report should provide a detailed description of the SAE and include a concise summary 
of hospital records and other relevant documents. If a subject died and an autopsy has been 
performed, copies of the autopsy report and death certificate are to be sent to Celgene Drug 
Safety as soon as these become available. Any follow-up data should be detailed in a subsequent 
SAE Report Form, or approved equivalent form, and sent to Celgene Drug Safety. 
Progressive disease is considered as a study endpoint and will not be reported as an SAE. 
However, any sign, symptom, or manifestation of progressive disease that meet any of the 
seriousness criteria will be reported as individual SAE. 
Where required by local legislation, the Investigator is responsible for informing the Institutional 
Review Board/Ethics Committee (IRB/EC) of the SAE and providing them with all relevant 
initial and follow-up information about the event. The Investigator must keep copies of all SAE 
information on file including correspondence with Celgene and the IRB/EC. 
10.5.1. 
Safety Queries 
Queries pertaining to SAEs will be communicated from Celgene Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than five (5) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone. 
10.5.2. 
Death Reports 
Deaths due to progressive disease will not be reported as an SAE unless considered related to LD 
chemotherapy or JCAR017 (ie, if assessed as lack of efficacy by the Investigator). Any sign, 
symptom, or manifestation of progressive disease that meet any of the seriousness criteria and 
result in death will be reported as individual SAEs. Any other AEs leading to death should be 
reported as an SAE according to Table 9. 
10.6. 
Expedited Reporting of Adverse Events 
For the purpose of regulatory reporting, Celgene Drug Safety will determine the expectedness of 
events suspected of being related to JCAR017 based on the Investigator’s Brochure. 
For countries within the European Economic Area (EEA), Celgene or its authorized 
representative will report in an expedited manner to Regulatory Authorities and Ethics 
Committees concerned, suspected unexpected serious adverse reactions (SUSARs) in accordance 
with Directive 2001/20/EC and the Detailed Guidance on collection, verification and 


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presentation of adverse reaction reports arising from clinical trials on investigational products 
(IPs) for human use (ENTR/CT3) and also in accordance with country-specific requirements. 
Celgene or its authorized representative shall notify the Investigator of the following 
information: 
• Any AE suspected of being related to the use of JCAR017 in this study or in other 
studies that is both serious and unexpected (ie, SUSAR); 
• Any finding from tests in laboratory animals that suggests a significant risk for 
human subjects including reports of mutagenicity, teratogenicity, or carcinogenicity. 
Where required by local legislation, the Investigator shall notify his/her IRB/EC promptly of 
these new serious and unexpected AE(s) or significant risks to subjects. 
The Investigator must keep copies of all pertinent safety information on file including 
correspondence with Celgene and the IRB/EC (see Section 14.3 for record retention 
information). 
Celgene Drug Safety Contact Information: 
For Celgene Drug Safety contact information, please refer to the Serious Adverse Event Report 
Form Completion Guidelines or to the Pregnancy Report Form Completion Guidelines. 
10.7. 
Adverse Event of Special Interest 
An adverse event of special interest (AESI) is one of scientific and medical interest specific to 
understanding of the Investigational Product and may require close monitoring and rapid 
communication by the Investigator to the Sponsor. An AESI may be serious or nonserious. The 
rapid reporting of AESIs allows ongoing surveillance of these events in order to characterize and 
understand them in association with the use of this investigational product. 
Adverse events of special interest for JCAR017 include but are not limited to: 
• Infusion reaction 
• Cytokine release syndrome (CRS) 
• Neurological toxicity (NT) 
• Macrophage activation syndrome (MAS) 
• Tumor lysis syndrome (TLS) 
Further information regarding the list of AESI can be found in the statistical analysis plan (SAP). 
10.8. 
Potential Risks and Management of Treatment Toxicities 
A summary of potential risks and management of treatment toxicity is provided below. 
Expected toxicities are described in the Reference Safety Information (RSI) in the Investigator’s 
Brochure (IB). These toxicities include, but are not limited to, Grade 4 CRS, neurotoxicity (eg, 
encephalopathy and/or seizures), and hypotension. The expected toxicities may also result in 
secondary toxicities of Grade 4 renal toxicity, hepatic toxicity, or other organ involvement. 
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unexpected for the purpose of reporting SUSARs to regulatory authorities, and if considered 
related to JCAR017 treatment will be reported in expedited fashion. 
See the IB for a complete discussion of potential risks associated with JCAR017. 
10.8.1. 
Management of Toxicities Associated with JCAR017 
Cytokine release syndrome and NT are associated with CAR T cell therapies. Celgene has 
developed specific toxicity management guidelines for CRS and NT associated with Celgene 
cellular products based on current clinical experience across the clinical development programs 
(Appendix M). These recommendations are based on the CRS revised grading system (Lee, 
2014) and the CTCAE and need to be used for grading of CRS and NT to guide management in 
this trial. 
If available and adopted as per site standard practice, CRS and NT grading according to the 
American Society for Transplantation and Cellular Therapy Consensus Grading System (Lee, 
2019) should also be recorded in the CRF to inform future modifications of the management 
guidelines. 
10.8.1.1. Cytokine Release Syndrome 
Administration of JCAR017 is associated with CRS. Cytokine release syndrome is characterized 
by fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, 
myalgia/arthralgia, anorexia, and neurologic abnormalities (eg, altered mental status, aphasia, 
altered level of consciousness, and seizures or seizure-like activity). Cytokine release syndrome 
generally occurs within 2 weeks after CAR T cell infusion and in severe cases may be life- 
threatening. 
Subjects at high risk of developing sCRS include those who develop the following (Davila, 
2014): 
• Fever (≥ 38 ºC) for at least 3 days 
• Changes in 2 different cytokines of at least 75-fold or a maximum change in 1 
cytokine of at least 250-fold 
• One or more clinical signs of toxicity such as: 
− Hypotension (requiring vasopressor support) 
− Hypoxia (pO2 < 90%) 
− Neurologic disorders (including mental status changes, obtundation, and seizures) 
Elevated CRP (≥ 20 mg/dL) and ferritin levels (> 5000 ng/mL) are also reliable indicators of 
sCRS. Thus, close observation of these subjects is strongly recommended. 
Please refer to Appendix M for detailed description of CRS, grading and treatment 
recommendations. Note: Cetuximab is not indicated for the treatment of CRS. 
10.8.1.2. Fever 
The possibility of CRS should be considered for all subjects with fever (≥ 38.5°C) following 
JCAR017 infusion. Subjects should be monitored closely for hemodynamic instability and 


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changing neurologic status. Febrile subjects, neutropenic or otherwise, should be evaluated 
promptly for infection and managed per institutional or standard clinical practice. 
10.8.1.3. Cytopenias 
Severe (Grade ≥ 3) cytopenias, including anemia, leukopenia, neutropenia, and 
thrombocytopenia, can occur with both JCAR017 and lymphodepleting chemotherapy, and 
delayed recovery has been observed. Complete blood counts (CBCs) should be monitored after 
JCAR017 infusion until count recovery. Institutional guidelines should be followed in the event 
of Grade ≥ 3 cytopenias. 
10.8.1.4. Infections 
Life-threatening and fatal infections have been observed. Severe infections may include 
bacterial, fungal (including pneumocystis jirovecii), and viral infections (eg, cytomegalovirus 
[CMV], hepatitis B virus [HBV], respiratory viruses, and other viruses). A high index of 
suspicion is warranted in the event of prolonged or recurrent cytopenias, especially in 
conjunction with hypogammaglobulinemia, severe lymphopenia, and/or recent use of 
corticosteroids. Viral reactivation and other serious opportunistic infections should be considered 
in these settings, and prophylactic, pre-emptive, or symptomatic treatment with antimicrobial, 
antifungal, anti-pneumocystic, and/or antiviral therapies should be considered per local 
institutional guidelines. 
10.8.1.5. Neurologic Toxicities 
CAR T cell therapy is associated with neurologic toxicities. Neurologic symptoms can vary and 
may include altered mental status, aphasia, altered level of consciousness, and seizures or 
seizure-like activity. Neurologic toxicities can accompany CRS (precede or follow other CRS 
symptoms) or can occur in isolation. Neurologic symptoms generally occur within 3 weeks after 
CAR T cell infusion and in severe cases may be life-threatening. 
Please refer to Appendix M for detailed description of neurologic toxicities, grading and 
treatment recommendations. Note: Cetuximab is not indicated for the treatment of neurologic 
toxicities. 
10.8.1.6. Macrophage Activation Syndrome 
Macrophage activation syndrome (MAS) is a serious disorder potentially associated with 
uncontrolled activation and proliferation of CAR T cells and subsequent activation of 
macrophages. MAS is typically characterized by high-grade, non-remitting fever, cytopenia, and 
hepatosplenomegaly. Laboratory abnormalities found in MAS include elevated inflammatory 
cytokine levels, serum ferritin, soluble IL-2 receptor (sCD25), triglycerides, and decreased 
circulating NK cells. Other findings include variable levels of transaminases, signs of acute liver 
failure, coagulopathy, and disseminated intravascular coagulopathy. There are no definitive 
diagnostic criteria for MAS; it is typically diagnosed using published criteria for hemophagocytic 
lymphohistiocytosis (Schulert, 2015). While there is considerable overlap in clinical 
manifestations and laboratory findings between MAS and CRS, other distinguishing MAS 
physical findings such as hepatosplenomegaly and lymphadenopathy are not common in adult 
subjects treated with activated T cell therapies. 


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Subjects treated with JCAR017 should be monitored for MAS, and cytokine-directed therapy 
should be considered as clinically indicated. 
10.8.1.7. Infusion Reactions 
Administration of JCAR017 may cause infusion reactions, such as fever, rigors, rash, urticaria, 
dyspnea, hypotension, and/or nausea. 
To minimize the risk of infusion reactions, all subjects should be premedicated with 
acetaminophen and diphenhydramine prior to JCAR017 infusion (see Section 7.3.2). Mild 
infusion reactions should be managed expectantly with antipyretics, antihistamines, and anti- 
emetics. Corticosteroids should be avoided because of the potential impact on efficacy of infused 
JCAR017 cells. Rigors may be treated with meperidine. 
The following guidelines should be followed for infusion reactions: 
• Grade 1: administer symptomatic treatment; continue JCAR017 infusion of both 
CD8+ and CD4+ components at the same dose and rate 
• Grade 2: stop administration of JCAR017; administer symptomatic treatment, and 
resume JCAR017 administration of both CD8+ and CD4+ components at a reduced 
rate of administration only after symptoms resolution 
• Grade 3: stop administration of JCAR017, administer symptomatic treatment, and 
resume at a reduced rate of administration only after symptoms resolve. If Grade 3 
reaction recurs, discontinue JCAR017 infusion; no further CD8+ or CD4+ 
components of JCAR017 should be administered 
• Grade 4: discontinue administration of JCAR017 and administer symptomatic 
treatment as necessary; no further CD8+ or CD4+ components of JCAR017 should be 
administered. 
10.8.1.8. Tumor Lysis Syndrome 
Both LD chemotherapy and JCAR017 may cause TLS in subjects with high disease burden. 
Subjects should be closely monitored for laboratory evidence of TLS (hyperuricemia, 
hyperkalemia, hyperphosphatemia, and hypocalcemia; see Appendix L), and subjects at high risk 
for developing TLS, such as those with high disease burden and high cell turnover, should 
receive prophylactic treatment including administration of allopurinol and hydration, per 
standard clinical practice, per institutional standards. 
10.8.1.9. B-Cell Aplasia 
B-cell aplasia is an expected potential off-tumor, on-target toxicity. Prolonged B-cell aplasia has 
been observed in other CD19-directed CAR T cell programs (Davila, 2014; Grupp, 2013). Serum 
immunoglobulin levels will be obtained from all subjects prior to and at various timepoints 
following JCAR017 infusion. Hypogammaglobulinemic subjects (serum immunoglobulin G 
[IgG] < 500 mg/dL) should be considered for intravenous immunoglobulin replacement therapy 
per institutional guidelines. 


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10.8.1.10. Graft-Versus-Host Disease 
The likelihood of GVHD occurring with CAR T cell therapy is low, but it remains a theoretical 
risk. Subjects who have undergone allogeneic HSCT and who have active, acute or chronic 
GVHD at screening are excluded from enrolling in this protocol. However, due to residual donor 
engraftment, some or all T cells of JCAR017 may be of donor origin. Subjects who received a 
previous allogeneic HSCT will be assessed for donor chimerism at screening and will be 
monitored closely throughout the study for signs of GVHD. 
10.8.1.11. Uncontrolled T Cell Proliferation 
JCAR017 could theoretically proliferate out of control. If uncontrolled JCAR017 proliferation 
occurs, subjects may be treated with high-dose steroids (eg, methylprednisolone 1-3 mg/kg/day, 
tapered over 7 days) or LD doses of cyclophosphamide (1 to 3 g/m2 IV). If an Investigator 
suspects uncontrolled JCAR017 proliferation, Celgene should be contacted immediately. In an 
animal model the EGFR antibody cetuximab was used to ablate EGFRt-expressing CAR T cells 
in vivo (Wang, 2011). Currently, there is no data available on use of cetuximab or other EGFR- 
directed antibodies for depletion of JCAR017 CAR T cells in humans. 
10.8.1.12. Replication-Competent Lentivirus, Clonality and Insertional Oncogenesis 
Lentiviral vectors used in gene transfer are engineered to be replication-defective; however, 
generation of RCL during manufacturing is still a possibility. Modern vector production systems 
have been improved to reduce the risk of RCL generation. To date, there have been no reports of 
RCL generated during lentiviral vector manufacturing, which may be due, at least in part, to the 
use of self-inactivating vectors such as the lentiviral vector used in the production of JCAR017 
(Rothe, 2013). 
Concerns for possible vector integration into the host genome have arisen due to preclinical 
studies that have shown retrovirus-mediated malignant transformation in mice (Li, 2002; 
Modlich, 2005) and monkeys (Donahue, 1992), and a single clinical study reporting 
development of leukemia in subjects with X-linked severe combined immunodeficiency (SCID) 
who received retroviral-modified CD34+ hematopoietic stem cells (Hacein-Bey-Abina, 2003) 
including one subject who died (Couzin, 2005). Of note, no instances of RCL generation during 
production or lentivirus-mediated malignant transformation in animals or subjects have been 
reported to date. 
Data has recently been published on the integration sites of retroviral and lentiviral vectors used 
for T cell modification in clinical trials (McGarrity, 2013; Scholler, 2012; Wang, 2009). No 
clonality of integration sites was observed. In addition, there did not appear to be enrichment of 
integration sites near genes involved in clonal expansion or persistence. 
10.8.1.13. Risks Associated with Lymphodepleting Chemotherapy 
Subjects will receive fludarabine and cyclophosphamide prior to treatment with JCAR017 to 
facilitate LD chemotherapy and CAR T cell engraftment. Refer to the SmPC for specific details 
surrounding the risks of fludarabine phosphate and cyclophosphamide. 


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10.8.1.14. New Malignancies 
New malignancies must be reported as SAEs. This includes any second primary malignancy, 
regardless of causal relationship to IP (study drug[s]), occurring at any time for the duration of 
the study, from the time of signing the ICF until study end. These events must also be 
documented in the appropriate page(s) of the CRF and subject’s source documents. 
Documentation on the diagnosis of the new malignancy must be provided at the time of reporting 
as a serious adverse event (eg, any confirmatory histology or cytology results, x-rays, CT scans, 
etc.). Celgene will request a sample of the neoplastic tissue for causality analysis related to use of 
integrating vector to determine if insertional oncogenesis is suspected. 


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11. 
DISCONTINUATIONS 
11.1. 
Treatment Discontinuation 
The following events are considered sufficient reasons for discontinuing a subject from the LD 
chemotherapy or JCAR017: 
• Adverse event 
• Subject withdrawal of consent 
• Manufacturing failure 
• Death 
• Lost to follow-up 
• Other (to be specified on the CRF) 
The reason for discontinuation of treatment should be recorded in the CRF and in the source 
documents. 
The decision to discontinue a subject from treatment remains the responsibility of the treating 
physician, which will not be delayed or refused by Celgene. However, prior to discontinuing a 
subject, the Investigator may contact the Medical Monitor and forward appropriate supporting 
documents for review and discussion. 
11.2. 
Study Discontinuation 
The following events are considered sufficient reasons for discontinuing a subject from the 
study: 
• Screen failure 
• Adverse event 
• Subject withdrawal of consent 
• Death 
• Lost to follow-up 
• Study termination by Sponsor 
• Other (to be specified on the CRF) 
The reason for study discontinuation should be recorded in the CRF and in the source 
documents. 


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12. 
EMERGENCY PROCEDURES 
12.1. 
Emergency Contact 
In emergency situations, the Investigator should contact the responsible Clinical Research 
Physician/Medical Monitor or designee by telephone at the number(s) listed on the Emergency 
Contact Information page of the protocol (after title page). 
In the unlikely event that the Clinical Research Physician/Medical Monitor or designee cannot be 
reached, please contact the global Emergency Call Center by telephone at the number listed on 
the Emergency Contact Information page of the protocol (after title page). This global 
Emergency Call Center is available 24 hours a day and 7 days a week. The representatives are 
responsible for obtaining your call-back information and contacting the on-call sponsor/contract 
research organization Medical Monitor, who will then contact you promptly. 
Note: The back-up 24-hour global emergency contact call center should only be used if you are 
not able to reach the Clinical Research Physician(s) or Medical Monitor or designee for 
emergency calls. 
12.2. 
Emergency Identification of Investigational Products 
This is an open-label study; therefore, the JCAR017 cell product will be identified on the 
package labeling. 


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13. 
REGULATORY CONSIDERATIONS 
13.1. 
Good Clinical Practice 
The procedures set out in this study protocol pertaining to the conduct, evaluation, and 
documentation of this study are designed to ensure that Celgene, its authorized representative, 
and Investigator abide by Good Clinical Practice (GCP), as described in ICH Guideline E6 and 
in accordance with the general ethical principles outlined in the Declaration of Helsinki. The 
study will receive approval from an IRB/EC prior to commencement. The Investigator will 
conduct all aspects of this study in accordance with applicable national, state, and local 
regulations of the pertinent regulatory authorities. 
13.2. 
Investigator Responsibilities 
Investigator responsibilities are set out in the ICH Guideline for Good Clinical Practice and in 
the local regulations. Celgene staff or an authorized representative will evaluate and approve all 
Investigators who in turn will select their staff. 
The Investigator should ensure that all persons assisting with the study are adequately informed 
about the protocol, amendments, study treatments, as well as study-related duties and functions, 
including obligations of confidentiality of Celgene information. The Investigator should maintain 
a list of Sub-Investigators and other appropriately qualified persons to whom he or she has 
delegated significant study-related duties. 
The Investigator is responsible for keeping a record of all subjects who sign an informed consent 
form and are screened for entry into the study. Subjects who fail screening must have the 
reason(s) recorded in the subject’s source documents. 
The Investigator, or a designated member of the Investigator’s staff, must be available during 
monitoring visits to review data, resolve queries and allow direct access to subject records (eg, 
medical records, office charts, hospital charts, and study-related charts) for source data 
verification. The Investigator must ensure timely and accurate completion of CRFs and queries. 
The information contained in the protocol and amendments (with the exception of the 
information provided by Celgene on public registry websites) is considered Celgene confidential 
information. Only information that is previously disclosed by Celgene on a public registry 
website may be freely disclosed by the Investigator or its institution, or as outlined in the Clinical 
Trial Agreement. Celgene protocol, amendment and IB information is not to be made publicly 
available (for example on the Investigator’s or their institution’s website) without express written 
approval from Celgene. Information proposed for posting on the Investigator’s or their 
institution’s website must be submitted to Celgene for review and approval, providing at least 5 
business days for review. 
At the time results of this study are made available to the public, Celgene will provide 
Investigators with a summary of the results that is written for the lay person. The Investigator is 
responsible for sharing these results with the subject and/or their caregiver as agreed by the 
subject. 


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13.3. 
Subject Information and Informed Consent 
The Investigator must obtain informed consent of a subject and/or a subject’s legal representative 
prior to any study related procedures. 
Documentation that informed consent occurred prior to the study subject’s entry into the study 
and of the informed consent process should be recorded in the study subject’s source documents 
including the date. The original ICF signed and dated by the study subject and by the person 
consenting the study subject prior to the study subject’s entry into the study, must be maintained 
in the Investigator’s study files and a copy given to the study subject. In addition, if a protocol is 
amended and it impacts on the content of the informed consent, the ICF must be revised. Study 
subjects participating in the study when the amended protocol is implemented must be re- 
consented with the revised version of the ICF. The revised ICF signed and dated by the study 
subject and by the person consenting the study subject must be maintained in the Investigator’s 
study files and a copy given to the study subject. 
13.4. 
Confidentiality 
Celgene affirms the subject's right to protection against invasion of privacy and to be in 
compliance with ICH and other local regulations (whichever is most stringent). Celgene requires 
the Investigator to permit Celgene's representatives and, when necessary, representatives from 
regulatory authorities, to review and/or copy any medical records relevant to the study in 
accordance with local regulations. 
Should direct access to medical records require a waiver or authorization separate from the 
subject’s signed ICF, it is the responsibility of the Investigator to obtain such permission in 
writing from the appropriate individual. 
13.5. 
Protocol Amendments 
Any amendment to this protocol must be approved by the Celgene Clinical Research 
Physician/Medical Monitor. Amendments will be submitted to the IRB/EC for written approval. 
Written approval must be obtained before implementation of the amended version occurs. The 
written signed approval from the IRB/EC should specifically reference the Investigator name, 
protocol number, study title and amendment number(s) that is applicable. Amendments that are 
administrative in nature do not require IRB/EC approval but will be submitted to the IRB/EC for 
information purposes. 
13.6. 
Institutional Review Board and Independent Ethics Committee 
Review and Approval 
Before the start of the study, the study protocol, ICF, and any other appropriate documents will 
be submitted to the IRB/EC with a cover letter or a form listing the documents submitted, their 
dates of issue, and the site (or region or area of jurisdiction, as applicable) for which approval is 
sought. If applicable, the documents will also be submitted to the authorities in accordance with 
local legal requirements. 
JCAR017 cell product can only be supplied to an Investigator by Celgene or its authorized 
representative after documentation on all ethical and legal requirements for starting the study has 


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been received by Celgene or its authorized representative. This documentation must also include 
a list of the members of the IRB/EC and their occupation and qualifications. If the IRB/EC will 
not disclose the names, occupations and qualifications of the committee members, it should be 
asked to issue a statement confirming that the composition of the committee is in accordance 
with GCP. For example, the IRB General Assurance Number may be accepted as a substitute for 
this list. Formal approval by the IRB/EC should mention the protocol title, number, amendment 
number (if applicable), study site (or region or area of jurisdiction, as applicable), and any other 
documents reviewed. It must mention the date on which the decision was made and must be 
officially signed by a committee member. Before the first subject is enrolled in the study, all 
ethical and legal requirements must be met. 
The IRB/EC and, if applicable, the authorities, must be informed of all subsequent protocol 
amendments in accordance with local legal requirements. Amendments must be evaluated to 
determine whether formal approval must be sought and whether the ICF should also be revised. 
The Investigator must keep a record of all communication with the IRB/EC and, if applicable, 
between a Coordinating Investigator and the IRB/EC. This statement also applies to any 
communication between the Investigator (or Coordinating Investigator, if applicable) and 
regulatory authorities. 
Any advertisements used to recruit subjects for the study must be reviewed by Celgene and the 
IRB/EC prior to use. 
13.7. 
Ongoing Information for Institutional Review Board and Ethics 
Committee 
If required by legislation or the IRB/EC, the Investigator must submit to the IRB/EC: 
• Information on serious or unexpected adverse events as soon as possible; 
• Periodic reports on the progress of the study; 
• Deviations from the protocol or anything that may involve added risk to subjects. 
13.8. 
Termination of the Study 
Celgene reserves the right to terminate this study prematurely at any time for reasonable medical 
or administrative reasons. Any premature discontinuation will be appropriately documented 
according to local requirements (eg, IRB/EC, regulatory authorities, etc). 
In addition, the Investigator or Celgene has the right to discontinue a single site at any time 
during the study for medical or administrative reasons such as: 
• Unsatisfactory enrollment; 
• GCP noncompliance; 
• Inaccurate or incomplete data collection; 
• Falsification of records; 
• Failure to adhere to the study protocol. 


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14. 
DATA HANDLING AND RECORDKEEPING 
14.1. 
Data and Documents 
The Investigator must ensure that the records and documents pertaining to the conduct of the 
study and the distribution of the JCAR017 cell product are complete, accurate, filed and retained. 
Examples of source documents include: hospital records; clinic and office charts; laboratory 
notes; memoranda; evaluation checklists; dispensing records; recorded data from automated 
instruments; copies or transcriptions certified after verification as being accurate copies; 
microfiche; x-ray film and reports; and records kept at the pharmacy, and the laboratories, as 
well as copies of CRFs or CD-ROM. 
14.2. 
Data Management 
Data will be collected via CRF and entered into the clinical database per Celgene standard 
operating procedures (SOPs). This data will be electronically verified through use of 
programmed edit checks specified by the clinical team. Discrepancies in the data will be brought 
to the attention of the clinical team, and investigational site personnel, if necessary. Resolutions 
to these issues will be reflected in the database. An audit trail within the system will track all 
changes made to the data. 
14.3. 
Record Retention 
Essential documents must be retained by the Investigator according to the period of time outlined 
in the clinical trial agreement. The Investigator must retain these documents for the time period 
described above or according to local laws or requirements, whichever is longer. Essential 
documents include, but are not limited to, the following: 
• Signed ICFs for all subjects; 
• Subject identification code list, screening log (if applicable), and enrollment log; 
• Record of all communications between the Investigator and the IRB/EC; 
• Composition of the IRB/EC; 
• Record of all communications between the Investigator, Celgene, and their authorized 
representative(s); 
• List of Sub-Investigators and other appropriately qualified persons to whom the 
Investigator has delegated significant study-related duties, together with their roles in 
the study, curriculum vitae, and their signatures; 
• Copies of CRFs (if paper) and of documentation of corrections for all subjects; 
• JCAR017 accountability records; 
• Record of any body fluids or tissue samples retained; 
• All other source documents (subject records, hospital records, laboratory records, 
etc.); 


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• All other documents as listed in Section 8 of the ICH consolidated guideline on GCP 
(Essential Documents for the Conduct of a Clinical Trial). 
The Investigator must notify Celgene if he/she wishes to assign the essential documents to 
someone else, remove them to another location or is unable to retain them for a specified period. 
The Investigator must obtain approval in writing from Celgene prior to destruction of any 
records. If the Investigator is unable to meet this obligation, the Investigator must ask Celgene 
for permission to make alternative arrangements. Details of these arrangements should be 
documented. 
All study documents should be made available if required by relevant health authorities. 
Investigator or institution should take measures to prevent accidental or premature destruction of 
these documents. 


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
All aspects of the study will be carefully monitored by Celgene or its authorized representative 
for compliance with applicable government regulations with respect to current GCP and SOPs. 
15.1. 
Study Monitoring and Source Data Verification 
Celgene ensures that appropriate monitoring procedures are performed before, during and after 
the study. All aspects of the study are reviewed with the Investigator and the staff at a study 
initiation visit and/or at an Investigators’ Meeting. Prior to enrolling subjects into the study, a 
Celgene representative will review the protocol, CRFs, procedures for obtaining informed 
consent, record keeping, and reporting of AEs/SAEs with the Investigator. 
Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan. 
Accuracy will be checked by performing source data verification that is a direct comparison of 
the entries made onto the CRFs against the appropriate source documentation. Any resulting 
discrepancies will be reviewed with the Investigator and/or his/her staff. Any necessary 
corrections will be made directly to the CRFs or via queries by the Investigator and/or his/her 
staff. Monitoring procedures require that informed consents, adherence to inclusion/exclusion 
criteria and documentation of SAEs and their proper recording be verified. Additional 
monitoring activities may be outlined in a study-specific monitoring plan. 
15.2. 
Audits and Inspections 
In addition to the routine monitoring procedures, a Good Clinical Practice Quality Assurance 
unit exists within Celgene. Representatives of this unit will conduct audits of clinical research 
activities in accordance with Celgene SOPs to evaluate compliance with Good Clinical Practice 
guidelines and regulations. 
The Investigator is required to permit direct access to the facilities where the study took place, 
source documents, CRFs and applicable supporting records of study subject participation for 
audits and inspections by IRB/ECs, regulatory authorities (eg, FDA, European Medicines 
Agency [EMA]) and company authorized representatives. The Investigator should make every 
effort to be available for the audits and/or inspections. If the Investigator is contacted by any 
regulatory authority regarding an inspection, he/she should contact Celgene immediately. 


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16. 
PUBLICATIONS 
As described in Section 13.2, all protocol- and amendment-related information, with the 
exception of the information provided by Celgene on public registry websites, is considered 
Celgene confidential information and is not to be used in any publications. Celgene protocol- 
related information proposed for use in a publication must be submitted to Celgene for review 
and approval, and should not be utilized in a publication without express written approval from 
Celgene, or as described in the Clinical Trial Agreement. 
Celgene will ensure Celgene-sponsored studies are considered for publication in the scientific 
literature in a peer-reviewed journal, irrespective of the results. At a minimum, this applies to 
results from all Phase 3 clinical studies, and any other study results of significant medical 
importance. This also includes results relating to investigational medicines whose development 
programs have been discontinued. 
Study results may also be presented at one or more medical congresses, and may be used for 
scientific exchange and teaching purposes. Additionally, this study and its results may be 
submitted for inclusion in all appropriate health authority study registries, as well as publication 
on health authority study registry websites, as required by local health authority regulations. 
Eligibility for external authorship, as well as selection of first authorship, will be based on 
several considerations, including, but not limited to, contribution to protocol development, study 
recruitment, data quality, participation in data analysis, participation in study steering committee 
(when applicable) and contribution to abstract, presentation and/or publication development. 


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from recent clinical studies targeting CD19. Oncoimmunology. 2012 Dec 1;1(9):1577-83. 
Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity 
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APPENDIX A.  TABLE OF ABBREVIATIONS 
 
Abbreviation or Specialist Term 
Explanation 
ABC 
Activated B-cell 
ADL 
Activities of daily life 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALL 
Acute lymphoblastic leukemia 
ALT 
Alanine aminotransferase (SGPT) 
ANC 
Absolute neutrophil count 
aPTT 
Activated partial thromboplastin time 
ASCT 
Autologous stem cell transplant 
AST 
Aspartate aminotransferase (SGOT) 
ATA 
Anti-therapeutic antibody 
AUC 
Area under the curve 
B-NHL 
B-cell non-Hodgkin lymphoma 
BCM 
B-cell malignancies 
β-hCG 
Beta human chorionic gonadotropin 
BMA 
Bone marrow aspirate 
BMB 
Bone marrow biopsy 
BOR 
Best overall response 
BUN 
Blood urea nitrogen 
CAR 
Chimeric antigen receptor 
CBC 
Complete blood count 
CI 
Confidence interval 
CLL 
Chronic lymphocytic leukemia 
Cmax 
Maximum plasma concentration of drug 
CNS 
Central nervous system 
COO 
Cell of origin 
CR 
Complete response 
CrCl 
Creatinine clearance 
CRF 
Case report form 
CRP 
C-reactive protein 
CRR 
Complete response rate 


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Abbreviation or Specialist Term 
Explanation 
CRS 
Cytokine release syndrome 
CRu 
Complete response unconfirmed 
CSF 
Cerebrospinal fluid 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DHL 
Double hit lymphoma 
DL 
Dose level 
DLBCL 
Diffuse large B-cell lymphoma 
DLCO 
Diffusion capacity of carbon monoxide 
DLI 
Donor lymphocyte infusions 
DLT 
Dose-limiting toxicity 
DMSO 
Dimethyl sulfoxide 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety and Monitoring Plan 
EBV 
Epstein-Barr virus 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EEA 
European Economic Area 
EFS 
Event-free survival 
eGFR 
Estimated glomerular filtration rate 
EGFRt 
Truncated epidermal growth factor receptor 
EMA 
European Medicines Agency 
EORTC QLQ-C30 
European Organisation for Research and Treatment of Cancer – 
Quality of Life C30 
EOS 
End of study 
EQ-5D-5L 
European Quality of Life-5 Dimensions health state classifier to 
5 Levels 
EQ VAS 
EQ visual analogue scale 
ET 
Early termination 


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Abbreviation or Specialist Term 
Explanation 
EU 
European Union 
FACT-LymS 
Functional Assessment of Cancer Therapy-Lymphoma 
“Additional concerns” subscale 
FDA 
Food and Drug Administration 
FEV1 
Forced expiratory volume in one second 
FISH 
Fluorescence in situ hybridization 
FL3B 
Follicular lymphoma Grade 3B 
Flu/Cy 
Fludarabine/cyclophosphamide 
GCB 
Germinal center B-cell 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GEP 
Gene expression profiling 
GVHD 
Graft-versus-host disease 
HBsAb 
Hepatitis B surface antibody 
HBsAg 
Hepatitis B surface antigen 
HBcAb 
Hepatitis B core antibody 
HCT 
Hematopoietic cell transplantation 
HCT-CI 
HCT-specific comorbidity index 
HCV 
Hepatitis C virus 
HDCT 
High-dose chemotherapy 
HGBL 
High-grade B-cell lymphoma with MYC and BCL2 and/or 
BCL6 rearrangements with DLBCL histology 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
HLH 
Hemophagocytic lymphohistiocytosis 
HRQoL 
Health-related quality of life 
HSCT 
Hematopoietic stem cell transplantation 
Hyper-CVAD 
Fractionated cyclophosphamide, vincristine, doxorubicin and 
dexamethasone 
IB 
Investigator’s Brochure 
ICE 
Immune Effector Cell-Associated Encephalopathy 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 


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Abbreviation or Specialist Term 
Explanation 
ICU 
Intensive care unit 
IFN-γ 
Interferon gamma 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IHC 
Immunohistochemistry 
IL 
Interleukin 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IP 
Investigational Product 
IPI 
International Prognostic Index 
IRB 
Institutional Review Board 
IRC 
Independent Review Committee 
IRT 
Interactive Response Technology 
IUD 
Intrauterine device 
IV 
Intravenous 
IVIG 
Intravenous immunoglobulins 
IWG 
International Working Group 
KPS 
Karnofsky performance score 
L 
Line of therapy 
LD 
Lymphodepleting 
LDH 
Lactate dehydrogenase 
LDi 
Longest transverse diameter of a lesion 
LTFU 
Long-term follow-up 
LTLS 
Laboratory tumor lysis syndrome 
LVEF 
Left ventricular ejection fraction 
MA 
Methotrexate and cytarabine 
mAb 
Monoclonal antibody 
MAS 
Macrophage activation syndrome 
MATRix regimen 
High dose metothrexate, high dose cytarabine, rituximab and 
thiotepa 
MedDRA 
Medical Dictionary for Regulatory Activities 


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Abbreviation or Specialist Term 
Explanation 
MHLW 
Ministry of Health, Labour and Welfare 
MMSE 
Mini Mental State Examination 
MRD 
Minimal residual disease 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose 
MUGA 
Multigated acquisition 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NHL 
Non-Hodgkin lymphoma 
NK 
Natural killer 
NOS 
Not otherwise specified 
nPR 
Nodular partial response 
NT 
Neurotoxicity 
NYHA 
New York Heart Association 
ORR 
Overall response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PBSC 
Peripheral blood stem cell 
PCNSL 
Primary central nervous system lymphoma 
PCP 
Pneumocystis pneumonia 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 
PD-1 
Programmed cell death protein 1 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PK 
Pharmacokinetic, pharmacokinetics 
PMBCL 
Primary mediastinal large B-cell lymphoma 
PO 
Per os 
PPDP 
Protocol Product Deviation Plan 
PR 
Partial response 
PRL 
Partial response with lymphocytosis 
PRO 
Patient-reported outcome 


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Abbreviation or Specialist Term 
Explanation 
PS 
Performance status 
PT 
Preferred term 
PT 
Prothrombin time 
Q 
Each, every 
qPCR 
Quantitative polymerase chain reaction 
RBC 
Red blood cell 
R-CHOP 
Rituximab, cyclophosphamide, doxorubicin hydrochloride, 
vincristine sulfate, prednisone 
R-EPOCH 
Rituximab, etoposide, prednisolone, oncovin, 
cyclophosphamide, hydroxydaunorubicin 
RCL 
Replication-competent lentivirus 
RCP 
Réunion de concertation pluridisciplinaire 
RNA 
Ribonucleic acid 
RNA-Seq 
RNA sequencing 
r/r 
Relapsed/refractory 
RSI 
Reference Safety Information 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Steering committee 
scFv 
Single chain variable fragment 
sCRS 
Severe cytokine release syndrome 
SD 
Stable disease 
SGOT 
Serum glutamic oxaloacetic transaminase 
SGPT 
Serum glutamic pyruvic transaminase 
SmPC 
Summary of Product Characteristics 
SOP 
Standard operating procedure 
SPD 
Sum of the product of the perpendicular diameters for multiple 
lesions 
SUSAR 
Suspected unexpected serious adverse reaction 
t1/2 
Half-life 
TEAE 
Treatment-emergent adverse event 
tFL 
Transformed follicular lymphoma 
TGF-α 
Transforming growth factor alpha 


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Abbreviation or Specialist Term 
Explanation 
THL 
Triple-hit lymphoma 
TLS 
Tumor lysis syndrome 
Tmax 
Time to peak concentration 
TNE 
Transplant not eligible 
TNF 
Tumor necrosis factor 
TNM 
Tumor, nodes, metastasis 
ULN 
Upper limit of normal 
US 
United States 
USPI 
United States Prescribing Information 
WBC 
White blood cell 
WBRT 
Whole brain radiation therapy 
WHO 
World Health Organization 


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APPENDIX B. PERFORMANCE STATUS BY EASTERN 
COOPERATIVE ONCOLOGY GROUP SCALE 
 
 
Score 
Description 
0 
Fully active, able to carry on all predisease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature, eg, light housework, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or 
chair. 
5 
Dead. 
Source:(Oken, 1982). 


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APPENDIX C. RECOMMENDATIONS FOR INITIAL EVALUATION, 
STAGING, AND RESPONSE ASSESSMENT OF 
HODGKIN AND NON-HODGKIN LYMPHOMA: THE 
LUGANO CLASSIFICATION 
The guidelines for Recommendations for Initial Evaluation, Staging, and Response Assessment 
of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification are outlined in a report 
(Cheson, 2014). 
Table C1: 
Criteria for Involvement of Site 
 
Tissue Site 
Clinical 
FDG Avidity 
Test 
Positive Finding 
Lymph nodes 
Palpable 
FDG-avid 
histologies 
Nonavid disease 
PET-CT 
CT 
Increase FDG uptake 
Unexplained node 
enlargement 
Spleen 
Palpable 
FDG-avid 
histologies 
Nonavid disease 
PET-CT 
CT 
Diffuse uptake, solitary 
mass, military lesions, 
nodules > 13 cm in vertical 
length, mass, nodules 
Liver 
Palpable 
FDG-avid 
histologies 
Nonavid disease 
PET-CT 
CT 
Diffuse uptake, mass 
Nodules 
CNS 
Signs, symptoms 
CT 
MRI 
CSF 
assessment 
Mass lesion(s) 
Leptomeningeal 
infiltration, mass lesions 
Cytology, flow cytometry 
Other (eg, skin, 
lung, GI tract, 
bone, bone 
marrow) 
Site dependent 
PET-CTa, 
biopsy 
Lymphoma involvement 
Abbreviations: CNS = central nervous system; CSF = cerebrospinal fluid; CT = computed tomography; FDG = 
fluorodeoxyglucose; GI = gastrointestinal; MRI = magnetic resonance imaging; PET = positron emission 
tomography. 
a PET-CT is adequate for determination of bone marrow involvement and can be considered highly suggestive for 
involvement of other extralymphatic sites. Biopsy confirmation of those sites can be considered if necessary. 


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Table C2: 
Revised Criteria for Response Assessment 
 
Response and Site 
PET-CT Based Response 
CT-Based Response 
Complete 
Complete metabolic response 
Complete radiologic response (all of 
the following) 
Lymph nodes and 
extralymphatic sites 
Score 1, 2, or 3a with or without a residual 
mass on 5PSb 
It is recognized that in Waldeyer's ring or 
extranodal sites with high physiologic uptake 
or with activation within spleen or marrow (eg, 
with chemotherapy or myeloid colony- 
stimulating factors), uptake may be greater 
than normal mediastinum and/or liver. In this 
circumstance, complete metabolic response 
may be inferred if uptake at sites of initial 
involvement is no greater than surrounding 
normal tissue even if the tissue has high 
physiologic uptake 
Target nodes/nodal masses must regress 
to ≤ 1.5 cm in the longest transverse 
diameter of a lesion (LDi) 
No extralymphatic sites of disease 
Nonmeasured lesion 
Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone marrow 
No evidence of FDG-avid disease in marrow 
Normal by morphology; if 
indeterminate, IHC negative 
Partial 
Partial metabolic response 
Partial remission (all of the following) 
Lymph nodes and 
extralymphatic sites 
Score 4 or 5b with reduced uptake compared 
with baseline and residual mass(es) of any size 
At interim, these findings suggest responding 
disease 
At end of treatment, these findings indicate 
residual disease 
≥ 50% decrease in SPD of up to 6 target 
measurable nodes and extranodal sites 
When a lesion is too small to measure 
on CT, assign 5 mm × 5 mm as the 
default value 
When no longer visible, 0 × 0 mm 
For a node > 5 mm × 5 mm, but smaller 
than normal, use actual measurement 
for calculation 
Nonmeasured lesion 
Not applicable 
Absent/normal, regressed, but no 
increase 
Organ enlargement 
Not applicable 
Spleen must have regressed > 50% in 
length beyond normal 
New lesions 
None 
None 


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Response and site 
PET-CT based response 
CT-based response 
Bone marrow 
Residual uptake higher than uptake in normal 
marrow but reduced compared with baseline 
(diffuse uptake compatible with reactive 
changes from chemotherapy allowed). If there 
are persistent focal changes in the marrow in 
the context of a nodal response, consideration 
should be given to further evaluation with MRI 
or biopsy or an interval scan 
Not applicable 
No response or 
stable disease 
No metabolic response 
Stable disease 
Target nodes/nodal 
masses, extranodal 
lesions 
Nonmeasured lesion 
Organ enlargement 
New lesions 
Bone marrow 
Score 4 or 5b with no significant change in 
FDG uptake from baseline at interim or end of 
treatment 
Not applicable 
Not applicable 
None 
No change from baseline 
< 50% decrease from baseline in SPD 
of up to 6 dominant measurable nodes 
and extranodal sites; no criteria for 
progressive disease are met 
No increase consistent with progression 
No increase consistent with progression 
None 
Not applicable 
Progressive 
disease 
Progressive metabolic response 
Progressive disease requires at 
least 1 of the following 
Individual target 
nodes/nodal masses 
Extranodal lesions 
Nonmeasured 
lesions 
Score 4 or 5b with an increase in intensity of 
uptake from baseline and/or 
New FDG-avid foci consistent with lymphoma 
at interim or end-of-treatment assessment 
None 
PPD progression: 
An individual node/lesion must be 
abnormal with: 
LDi > 1.5 cm and 
Increase by ≥ 50% from PPD nadir and 
An increase in LDi or SDi from nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions > 2 cm 
In the setting of splenomegaly, the 
splenic length must increase by > 50% 
of the extent of its prior increase 
beyond baseline (eg, a 15 cm spleen 
must increase to > 16 cm). If no prior 
splenomegaly, must increase by at least 
2 cm from baseline 
New or recurrent splenomegaly 
New or clear progression of preexisting 
nonmeasured lesions 


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Response and site 
PET-CT based response 
CT-based response 
New lesions 
Bone marrow 
New FDG-avid foci consistent with lymphoma 
rather than another etiology (eg, infection, 
inflammation). If uncertain regarding etiology 
of new lesions, biopsy or interval scan may be 
considered 
New or recurrent FDG-avid foci 
Regrowth of previously resolved lesions 
A new node > 1.5 cm in any axis 
A new extranodal site > 1.0 cm in any 
axis, if < 1.0 cm in any axis, its 
presence must be unequivocal and must 
be attributable to lymphoma 
Assessable disease of any size 
unequivocally attributable to lymphoma 
New or recurrent involvement 
Abbreviations: 5PS = 5-point scale; CT = computed tomography; FDG = fluorodeoxyglucose; GI = gastrointestinal; 
IHC = immunohistochemistry; LDi = longest transverse diameter of a lesion; MRI = magnetic resonance imaging; 
PET = positron emission tomography; PPD = cross product of the LDi and perpendicular diameter; SDi = shortest 
axis perpendicular to the LDi; SPD = sum of the product of the perpendicular diameters for multiple lesions. 
a  A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of 
an interim scan. However, in trials involving PET where deescalation is investigated, it may be preferable to 
consider a score of 3 as inadequate response (to avoid undertreatment). 
Measured dominant lesions: Up to 6 of the largest dominant nodes, nodal masses, and extranodal lesions 
selected to be clearly measurable in two diameters. Nodes should preferably be from disparate regions of the 
body and should include, where applicable, mediastinal and retroperitoneal areas. Non-nodal lesions include 
those in solid organs (eg, liver, spleen, kidneys, and lungs), GI involvement, cutaneous lesions, or those 
noted on palpation. Nonmeasured lesions: Any disease not selected as measured, dominant disease and truly 
assessable disease should be considered not measured. These sites include any nodes, nodal masses, and 
extranodal sites not selected as dominant or measurable or that do not meet the requirements for 
measurability but are still considered abnormal, as well as truly assessable disease, which is any site of 
suspected disease that would be difficult to follow quantitatively with measurement, including pleural 
effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and other lesions that cannot be 
confirmed and followed by imaging. In Waldeyer’s ring or in extranodal sites (eg, GI tract, liver, bone 
marrow), FDG uptake may be greater than in the mediastinum with complete metabolic response, but should 
be no higher than surrounding normal physiologic uptake (eg, with marrow activation as a result of 
chemotherapy or myeloid growth factors). 
b 
PET 5PS: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake > mediastinum but ≤ liver; 4, 
uptake moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, new areas of uptake 
unlikely to be related to lymphoma. 
Source: (Cheson, 2014). 


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APPENDIX D. MINI MENTAL STATE EXAMINATION 


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APPENDIX E. CLINICAL LABORATORY EVALUATIONS 
 
Laboratory Panel 
Analytes 
Chemistry 
Glucose, BUN, creatinine, sodium, potassium, chloride, calcium, total 
protein, albumin, total bilirubin, direct bilirubin, alkaline phosphatase, ALT 
(SGPT), AST (SGOT), magnesium, phosphate, bicarbonate, LDH, ß2- 
microglobulin, uric acid, triglycerides 
Hematology 
CBC with differential 
Coagulation 
PT, aPTT, INR, fibrinogen, and D-dimer 
Urinalysis* 
Appearance, pH, specific gravity, protein 
Glucose, ketones, RBCs, WBCs 
Casts, crystals, or other components 
Pregnancy* 
ß-hCG (serum) 
Viral serology 
HIV 
HBsAb, HBsAg, HBcAb, HCV antibody 
HLA typing* 
HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 
Inflammatory markers 
CRP, ferritin 
Donor chimerism* 
% stem cell donor 
Disease characterization 
Histology, cell of origin, immunochemistry, cytogenetics, molecular sub- 
typing 
Cerebrospinal fluid* 
RBCs, WBCs with differential, lymphoma cells, glucose, protein 
Immunoglobulins 
IgG, IgM, IgA 
* Local assessment only. 
Abbreviations: ALT (SGPT) = alanine aminotransferase (serum glutamic pyruvic transaminase); aPTT = activated 
partial thromboplastin time; AST (SGOT) = aspartate aminotransferase (serum glutamic oxaloacetic transaminase); 
ß-hCG = beta human chorionic gonadotropin; BUN = blood urea nitrogen; CBC = complete blood count; CRP = C- 
reactive protein; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B 
surface antigen; HCV = hepatitis C virus; HIV= human immunodeficiency virus; HLA = human leukocyte antigen; 
IgG = immunoglobulin G; INR = international normalized ratio; LDH = lactate dehydrogenase; PT = prothrombin 
time; RBC = red blood cell; WBC = white blood cell. 


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APPENDIX F. COCKCROFT-GAULT EQUATION FOR CALCULATING 
ESTIMATED CREATININE CLEARANCE 
 
 
Serum creatinine 
units 
Gender 
Estimated Creatinine Clearance (mL/min) 
mg/dL 
Male 
(140 − subject age [years]) × subject weight (kg) 
72 × subject serum creatinine (mg/dL) 
Female 
(140 − subject age [years]) × subject weight (kg) × 0.85 
72 × subject serum creatinine (mg/dL) 
μM/dL 
Male 
(140 − subject age [years]) × subject weight (kg) × 1.23 
Subject serum creatinine (μM/dL) 
Female 
(140 − subject age [years]) × subject weight (kg) × 1.04 
Subject serum creatinine (μM/dL) 


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APPENDIX G. HCT-CI SCORE CALCULATOR 
 
 
Co-morbidity 
Definition 
Yes 
Score 
Arrhythmia 
Atrial fibrillationa 
1 
Atrial fluttera 
Sick sinus syndromea 
Ventricular arrhythmiaa 
Cardiovascular 
Coronary artery diseasea 
1 
Congestive heart failurea 
Myocardial infarctiona 
Ejection fraction ≤ 50%b 
Inflammatory 
bowel disease 
Crohn’s diseasea 
1 
Ulcerative colitisa 
Diabetes 
Treated with insulin or oral hypoglycemic drugsb 
1 
Cerebro-vascular 
Transient ischemic attacksa 
1 
Cerebro-vascular ischemic or hemorrhagic strokea 
Depression/ 
anxiety 
Requiring psychological consultation and/or specific 
treatmentsb 
1 
Hepatic - mild 
Chronic hepatitisb 
1 
Bilirubin > ULN - 1.5 x ULNb 
AST/ALT > ULN - 2.5 x ULNb 
Obesity 
Body mass index >35 (adults)b 
1 
Body mass index-for-age ≥ 95% percentile (children)b 
Infection 
Requiring anti-microbial treatment before, during, and after the 
start of conditioningb 
1 
Rheumatologic 
Requiring Treatmenta 
2 
Peptic ulcer 
Confirmed by endoscopy and requiring treatmenta 
2 
Renal 
Serum creatinine > 2 mg/dl (or > 177µmol/L)b 
2 
On dialysisb 
Prior renal transplantationa 
Pulmonary - 
Moderate 
DLCO adjusted with Dinakara equation (adjusted DLCO = 
Predicted DLCO / [0.06965 x hemoglobin]) of 66-80% of 
predictedb 
2 
FEV1 66-80% of predictedb 


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Co-morbidity 
Definition 
Yes 
Score 
Dyspnea on slight activityb 
Pulmonary - 
Severe 
DLCO adjusted with Dinakara equation (adjusted DLCO = 
Predicted DLCO / [0.06965 x hemoglobin]) of ≤ 65% of 
predictedb 
3 
FEV1 ≤ 65% of predictedb 
Dyspnea at rest or requiring oxygen therapyb 
Heart valve 
disease 
Except asymptomatic mitral valve prolapse 
3 
Prior solid 
malignancy 
Treated with surgery, chemotherapy, and/or radiotherapy, 
excluding non-melanoma skin cancera 
3 
Hepatic - 
moderate/severe 
Liver cirrhosisb 
3 
Bilirubin > 1.5 x ULNb 
AST/ALT > 2.5 x ULNb 
Total Score 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; DLCO = diffusion capacity of 
carbon monoxide; FEV1 = forced expiratory volume in one second; ULN = upper limit of normal. 
a Diagnosed at any time in the patient’s past history. 
b Detected at the time of pretransplant assessment. 


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APPENDIX H. FRAILTY SCALE 
 
 
Frailty scale, validated by International Myeloma Working Group 
Category 
Score 
Age 
≤ 75 years 
76-80 years 
> 80 years 
0 
1 
2 
Charlson Comorbidity Index 
≤ 1 
> 1 
0 
1 
ECOG Performance Status Scale 
ECOG = 0 
ECOG = 1 
ECOG ≥ 2 
0 
1 
2 
Sum of Scores 
Non-frail 
Frail 
0-1 
≥ 2 
Abbreviations: ECOG = Eastern Cooperative Oncology Group. 
Source: (Larocca, 2016). 


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Charlson Comorbidity Index Scoring (Charlson, 1987) 
 
Condition 
Points 
Notes 
Congestive heart failure 
1 
Peripheral vascular disease or bypass 
1 
Cerebrovascular disease or transient 
ischemic disease 
1 
Hemiplegia 
2 
If hemiplegia do not count cerebrovascular 
disease or transient ischemic disease separately 
Pulmonary disease / asthma 
1 
Diabetes 
1 
Diabetes with end organ damage 
2 
If end organ damage do not count diabetes 
separately 
Renal disease 
2 
Mild liver disease 
2 
Severe liver disease 
3 
Gastric or peptic ulcer 
2 
Cancer (lymphoma, leukemia, solid 
tumor) 
2 
Nonmetastatic cancer only 
Metastatic solid tumor 
6 
If metastatic do not count cancer separately 
Dementia or Alzheimer’s disease 
1 
Rheumatic or connective tissue disease 
1 
HIV or AIDS 
6 
Hypertension 
1 
Skin ulcers / cellulitis 
2 
Depression 
1 
Warfarin 
1 
Source: (Charlson, 1987). 


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APPENDIX I. 
PATIENT-REPORTED OUTCOMES: EORTC QLQ C-30 


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APPENDIX J. PATIENT-REPORTED OUTCOMES: EQ-5D-5L 


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APPENDIX K. PATIENT-REPORTED OUTCOMES: FACT-LYMS 


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APPENDIX L. CAIRO-BISHOP DEFINITIONS OF TUMOR LYSIS 
SYNDROME 
 
Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome (LTLS) 
 
Laboratory 
Parameter 
Laboratory Result 
Uric acid 
≥ 476 μmol/L (≥ 8.0 mg/dL) or 25% increase from baseline 
Potassium 
≥ 6.0 mmol/L (≥ 6.0 mEq/L) or 25% increase from baseline 
Phosphorous 
≥ 1.45 mmol/L (≥ 4.5 mg/dL) or 25% increase from baseline 
Calcium 
≤ 1.75 mmol/L (≤ 7.0 mg/dL) or 25% decrease from baseline 
Laboratory tumor lysis syndrome (LTLS) is defined as either a 25% change or level above or 
below normal, as defined above, for any two or more serum values of uric acid, potassium, 
phosphate, and calcium within 3 days before or 7 days after the initiation of chemotherapy. This 
assessment assumes that a patient has or will receive adequate hydration (± alkalinization) and a 
hypouricaemic agent(s). 
 
Cairo-Bishop Definition of Clinical TLS 
 
The presence of laboratory TLS and one or more of the following criteria: 
1. Creatinine: ≥ 1.5 ULN (age > 12 years or age adjusted) 
2. Cardiac arrhythmia/sudden deatha 
3. Seizurea 
Abbreviations: TLS = tumor lysis syndrome; ULN = upper limit of normal. 
a Not directly attributable to a therapeutic agent. 
 
 
Cairo-Bishop Grading System for TLS 
 
Grade 
LTLS 
Creatinine 
Cardiac Arrhythmia 
Seizure 
0 
- 
≤ 1.5 × ULN 
None 
None 
1 
+ 
1.5 × ULN 
Intervention not indicated 
None 
2 
+ 
> 1.5 – 3.0 × ULN 
Non-urgent medical 
intervention indicated 
One brief generalized 
seizure; seizure(s) well 
controlled or infrequent; 
focal motor seizures not 
interfering with 
activities of daily life 
(ADL) 


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Cairo-Bishop Grading System for TLS (Continued) 
 
Grade 
LTLS 
Creatinine 
Cardiac Arrhythmia 
Seizure 
3 
+ 
> 3.0 – 6.0 × 
ULN 
Symptomatic and 
incompletely controlled 
medically or controlled 
with device 
Seizure in which consciousness is 
altered; poorly controlled seizure 
disorder; breakthrough generalized 
seizures despite medical intervention 
4 
+ 
> 6.0 × ULN 
Life-threatening 
Seizures of any kind that are 
prolonged, repetitive, or difficult to 
control 
5 
+ 
Deatha 
Deatha 
Deatha 
Abbreviations: ADL = activities of daily living; LTLS = laboratory tumor lysis syndrome; TLS = tumor lysis 
syndrome; ULN = upper limit of normal. 
a Probably or definitely attributable to clinical TLS. 
Source:(Cairo, 2004). 


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APPENDIX M. JCAR017 MANAGEMENT GUIDELINES FOR 
CYTOKINE RELEASE SYNDROME AND NEUROLOGIC 
TOXICITIES (V3.2) 
1. MANAGEMENT OF TOXICITIES ASSOCIATED WITH JCAR017 
Cytokine release syndrome (CRS) and neurologic toxicities (NT) are associated with chimeric 
antigen receptor (CAR) T cell therapies. Celgene has developed the toxicity management 
guidelines (TMG) for CRS and NT associated with Celgene cellular products based on current 
clinical experience across the clinical development programs. These recommendations are based 
on the CRS revised grading system (Lee, 2014) and the Common Terminology Criteria for 
Adverse Events (CTCAE) and need to be used for grading of CRS and NT to guide management 
in this trial. 
If available and adopted as per site standard practice, CRS and NT grading according to the 
American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading System 
(Lee, 2019) should also be recorded in the electronic case report form (eCRF) to inform future 
modifications of the management guidelines. 
 
2. CYTOKINE RELEASE SYNDROME 
Administration of cellular products such as CAR-expressing T cells can be associated with 
cytokine-associated toxicity due to systemic production and release of various cytokines into the 
circulation. Cytokine-associated toxicity, also known as CRS, is a toxicity that occurs as a result 
of immune activation (Lee, 2014; Gardner 2017). 
2.1. 
Pathophysiology of Cytokine Release Syndrome 
The hallmark of CRS is immune activation resulting in elevated inflammatory cytokines. Cytokine 
release syndrome clinically manifests when large numbers of lymphocytes (B-cells, T-cells, and/or 
natural killer cells) and/or myeloid cells (macrophages, dendritic cells, and monocytes) become 
activated and release inflammatory cytokines. Cytokine release syndrome has classically been 
associated with therapeutic monoclonal antibody (mAb) infusions, most notably anti-CD3 
(OKT3), anti-CD52 (alemtuzumab), anti-CD20 (rituximab), and the CD28 super-agonist, 
TGN1412. Cytokine release syndrome is also frequently observed following administration of bi- 
specific T cell engaging antibodies for leukemia, and adoptive cellular immunotherapies for 
cancer, most notably CAR T cells. Incidence, time to onset and severity of CRS due to CAR T 
cells is at least partially dependent on the infused cell dose and tumor burden/antigen density, 
presumably due to more rapid and higher levels of CAR T cell activation. Onset of CRS symptoms 
typically occurs days to occasionally weeks after the CAR T cell infusion, usually preceding 
maximal in vivo T cell expansion. Cytokine release syndrome is associated with elevated 
interferon gamma (IFN-γ), interleukin (IL)-6, and tumor necrosis alpha (TNF-α) levels, and 
increases in IL-2, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-10, IL-8, IL- 
5, and fractalkine although the pattern of elevated cytokines varies among subjects (Davila, 2014; 
Hay, 2017). IL-6 has been identified as a central mediator of toxicity in CRS. IL-6 is a pleiotropic 
cytokine with anti-inflammatory and proinflammatory properties. High levels of IL-6, present in 
the context of CRS, likely initiates a proinflammatory IL-6-mediated signaling cascade. 


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2.2. 
Clinical Presentation of Cytokine Release Syndrome 
Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, 
tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia. Clinical symptoms 
and severity of CRS are highly variable (Lee, 2014), and management can be complicated by 
concurrent conditions. In non-Hodgkin lymphoma (NHL) subjects treated with JCAR017, CRS 
usually occurs within two weeks after infusion (Abramson, 2017). 
• Fever, especially high fever (≥ 38.5 °C or ≥ 101.3 °F), is a commonly-observed 
hallmark of CRS, and many features of CRS mimic infection. Hence, infection must 
be considered in all subjects presenting with CRS symptoms, and appropriate cultures 
must be obtained and empiric antibiotic therapy initiated per institution standard of 
care. 
• Less common symptoms associated with CRS include cardiac dysfunction, adult 
respiratory distress syndrome, renal and/or hepatic failure, coagulopathies, 
disseminated intravascular coagulation, and capillary leak syndrome. 
• Neurologic toxicity has been observed concurrently with CRS; refer to Section 4. 
• CRS has been reported in some cases to be associated with findings of macrophage 
activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH), and the 
physiology of the syndromes may overlap; refer to Section 3. 
2.3. 
Clinical Management of Cytokine Release Syndrome 
Across various CD19 CAR T cell products, early manifestations of CRS can predict more severe 
toxicity for both CRS and NT. 
Subjects with B-cell acute lymphoblastic leukemia (ALL) and high burden of disease are at high 
risk of developing CRS (Frey, 2017). Subjects with NHL who have high baseline tumor burden 
(measured by the sum of product of the perpendicular diameters [SPD] or high serum lactate 
dehydrogenase [(LDH); ≥ 500 U/L] prior to the start of lymphodepletion) also have a higher risk 
for developing CRS and/or neurotoxicity (Siddiqi, 2017). 
High baseline levels of other commonly measured inflammatory markers, such as ferritin and C- 
reactive protein (CRP), were also associated with CRS. 
It should be noted that, although useful for identifying subjects at higher risk for developing CRS, 
CRP, ferritin, and serum cytokine levels should not be used for CRS clinical 
management/treatment decisions in the absence of other clinical signs and symptoms of CRS; for 
example, a subject with an elevated CRP but no concomitant symptoms may not require 
intervention (Park, 2017). Thus, close observation of these subjects is strongly recommended. 
A modification of the CTCAE CRS grading scale has been established to better reflect CAR T 
cell-associated CRS, as detailed in Table 1 (Lee, 2014). 


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Table 1: Grading Criteria for Cytokine Release Syndrome 
 
Symptoms/Signs 
Cytokine 
Release 
Syndrome 
(CRS) 
Grade 1 
(mild) 
CRS Grade 2 
(moderate) 
CRS Grade 3 
(severe) 
CRS Grade 4 
(life- 
threatening) 
CRS grade is defined by the most severe symptom 
(excluding fever) 
Vital Signs 
Temperature 
≥38.5 °C/101.3 °F 
Yes 
Any 
Any 
Any 
Systolic blood 
pressure (SBP) ≤ 
90 mmHg 
N/A 
Responds to 
intravenous 
(IV) fluids or 
single low-dose 
vasopressora 
Needs high- 
dosea or 
multiple 
vasopressors 
Life-threatening 
Need for oxygen to 
reach oxygen 
saturation (SaO2) 
> 90% 
N/A 
Fraction of 
inspired 
oxygen (FiO2) 
< 40% 
FiO2 ≥ 40% 
Needs ventilator 
support 
Organ 
Toxicity 
N/A 
Grade 2 
Grade 3 or 
transaminitis 
Grade 4 
Grade 4 
(excluding 
transaminitis) 
a Definition of high-dose vasopressors in Table 2. 
Table 2: High Dose Vasopressors (all doses required for ≥ 3 hours) 
 
Vasopressor 
Dose 
Norepinephrine monotherapy 
≥ 20 μg/min 
Dopamine monotherapy 
≥ 10 μg/kg/min 
Phenylephrine monotherapy 
≥ 200 μg/min 
Epinephrine monotherapy 
≥ 10 μg/min 
If on vasopressin 
Vasopressin + norepinephrine equivalent (NE) of ≥ 10 
μg/mina 
If on combination vasopressors (not vasopressin) 
Norepinephrine equivalent of ≥20 μg/mina 
a VASST Trial Vasopressor Equivalent Equation: Norepinephrine equivalent dose = [norepinephrine (μg/min)] + [dopamine (μg/kg/min) ÷ 2] + 
[epinephrine (μg/min)] + [phenylephrine (μg/min) ÷ 10]. 
Adapted from (Lee, 2014). 
Detailed CRS management guidelines are shown in Figure 1. Treatment should be individualized 
for each subject’s clinical needs. This guidance emphasizes the importance of early intervention 
for Grade 2 CRS, or in the setting of a rapid onset or rapid progression of CRS symptoms, to 
prevent the development of severe (Grade 3 or greater) CRS and NT. 


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In some cases, tocilizumab, an anti-IL-6R-antibody, may be required to treat toxicities such as 
severe CRS. Please refer to the currently approved Actemra® prescribing information (US) or 
RoActemra SmPC (EU). Actemra® has been approved by the Food and Drug Administration 
(FDA) for the treatment of CAR T cell-induced severe or life-threatening CRS in adults. 
RoAcetmra® has been approved by the European Medicines Agency (EMA) for the treatment of 
CAR T cell-induced severe or life-threatening CRS in adults. The preferred dose to intervene in 
adult subjects with CRS is 8 mg/kg (maximum 800 mg) IV. If no clinical improvement in the 
signs and symptoms of CRS occurs after the first dose, additional doses of tocilizumab may be 
administered (please see Figure 1, Actemra® prescribing information [US] and RoAcetmra® 
SmPC [EU]). 
Other anti-IL-6 agents, if available in the country, should be considered in the event of severe 
CRS not responding to tocilizumab and corticosteroids. Dosing of any other anti-IL-6 agent 
should be per prescribing information. 
In the most unresponsive severe cases additional treatments with T cell depleting therapies such 
as cyclophosphamide should be considered (Brudno, 2016). 


 
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Figure 1: JCAR017 Cytokine Release Syndrome Treatment Algorithm 
 
 
Abbreviations: ANC = absolute neutrophil count; BMA = bone marrow aspirate; CAR = chimeric antigen receptor; CRP = C-reactive protein; CRS = cytokine 
release syndrome; EEG = electroencephalogram; HLH = hemophagocytic lympho-histiocytosis; ICU = intensive care unit; IL-6 = interleukin 6; INR = 
international normalized ratio; IV = intravenous; MAS = macrophage activation syndrome; NT = neurotoxicity; PTT = partial thromboplastin time; q = every. 
 
 
 
 
 
 
 
 
 
 
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3. 
MACROPHAGE ACTIVATION SYNDROME 
/HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS 
Macrophage activation syndrome (MAS) or HLH is a rare, potentially fatal immune-mediated 
disease, which is caused by impaired natural killer and cytotoxic T-cell function. This syndrome 
has a wide range of causes, symptoms, and outcomes, but all lead to a hyperinﬂammatory 
response (with some characteristics that overlap with CRS and organ damage (Ramos-Casals, 
2014). Cases of MAS/HLH have been described in patients treated with CAR T-cell therapies 
(Neelapu, 2017). 
3.1. 
Pathophysiology of Macrophage Activation Syndrome/Hemophagocytic 
Lymphohistiocytosis 
Macrophage activation syndrome/hemophagocytic lymphohistiocytosis is divided into primary 
(genetic) and secondary (reactive) forms. Secondary MAS/HLH is subclassiﬁed as viral, 
autoimmune, or tumor related. MAS/HLH has both infectious and non-infectious triggers 
(Ramos-Casals, 2014). Viral infection is the most frequent trigger, either due to primary 
infection or after reactivation in immunosuppressed patients. Bacterial and fungal infections can 
also trigger MAS/HLH. Macrophage activation like syndrome (MALS) is a distinct entity that 
leads to early death in septic patients and must be carefully ruled out in patients who are prone to 
develop severe infections, including patients following CAR T-cell therapy (Karakike, 2019). 
Patients with hematological malignancies, in particular lymphoma, have a higher risk of 
developing MAS/HLH. 
3.2. 
Clinical Presentation and Diagnosis of Macrophage Activation 
Syndrome/Hemophagocytic Lymphohistiocytosis 
The presentation of secondary MAS/HLH is heterogeneous and characterized by a panoply of 
clinical signs and symptoms. The clinical syndrome can be acute or subacute with non-specific 
symptoms appearing over few days to 4 week(s) (Ramos-Casals, 2014). The cardinal features are 
continuous high fever (≥ 38.5 °C) and enlarged lymphohematopoietic organs 
(spleno/hepatomegaly, occasionally accompanied by adenopathy). Pulmonary, neurologic, 
cutaneous and gastrointestinal involvement may also be present. 
Laboratory markers associated with MAS/HLH include pancytopenia, hyperferritinemia, 
hypoﬁbrinogenemia and raised D-dimer levels, hypertriglyceridemia, and abnormalities in liver 
function. 
Detection of any ongoing infection acting as a trigger for MAS/HLH is critical (Figure 1). 
Standard tests should be used to screen for infections caused by the most common viruses such 
as herpes, cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Other infectious agents (eg, 
mycobacteria, parasites, and fungi, particularly Candida and Mucor) should be ruled out 
according to speciﬁc clinical or epidemiological features (Ramos-Casals, 2014; Lehmberg, 
2015). 
Bone marrow is the preferred anatomical site for investigation of suspected MAS/HLH. Bone 
marrow aspirate can be negative at the initial stage of MAS/HLH and should be repeated during 
the clinical course if there is a high suspicion of MAS/HLH. 


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The diagnosis of MAS/HLH (according to HLH-2004 consensus criteria, further revised in 2014 
for HLH associated with malignancies) (Lehmberg, 2015) can be established if either of the two 
criteria below is fulfilled: 
1. A molecular diagnosis consistent with MAS/HLH 
2. Diagnostic criteria for MAS/HLH fulfilled (five out of the eight criteria below): 
• High persistent fever (≥ 38.5 °C) 
• Splenomegaly 
• Cytopenias (affecting 2 of 3 lineages in the peripheral blood): Hemoglobin < 90 g/L, 
platelets < 100 x 109/L, neutrophils < 1.0 x 109/L 
• Triglycerides ≥ 3.0 mmol/L (ie, 265 mg/dL) or fibrinogen ≤ 1.5 g/L 
• Hemophagocytosis in bone marrow, spleen and/or lymph nodes 
• Low or absent NK-cell activity (according to local laboratory reference) 
• Ferritin ≥ 500 ng/mL 
• Soluble CD25 (ie, soluble IL-2 receptor) ≥ 2,400 U/mL 
3.3. 
Clinical Management of Macrophage Activation 
Syndrome/Hemophagocytic Lymphohistiocytosis 
Effective treatment of MAS/HLH requires multiple simultaneous approaches (Ramos-Casals, 
2014, Lehmberg, 2015). 
1. Supportive care is essential because of frequent life-threatening severe manifestations at 
presentation. 
2. The elimination of triggers (particularly infection) is crucial to remove the stimuli that 
initiate the abnormal immune system activation. Appropriate broad-spectrum antiviral, 
antibacterial, antifungal prophylaxis and treatment must be initiated. 
3. Suppression of the inﬂammatory response and cell proliferation by immunosuppressive 
and cytotoxic drugs, respectively, is necessary. First line treatment includes IL-6- 
blockade with tocilizumab. Glucocorticoids are also indicated for the initial treatment of 
MAS/HLH, irrespective of the cause (CRS Grade 4 treatment recommendations should 
be followed). IL-1 blockade with anakinra is suggested as second line treatment or in 
case of rapidly progressing clinical course. Anti-IL-6 antibody siltuximab might be 
considered as well as second line therapy. The use of cyclosporin, cyclophosphamide, 
etoposide and/or intrathecal methotrexate is not generally indicated in patients who 
develop MAS/HLH after CAR T-cell therapy, but may have to be employed in refractory 
cases. 
Newer emerging treatments include emapalumab (anti IFN-gamma antibody), which has 
been approved by FDA for the treatment of primary refractory or recurrent MAS/HLH 
(Benedetti, 2019). 


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4. NEUROLOGIC TOXICITIES 
CAR T cell therapy is associated with unique neurologic toxicities. Neurologic symptoms may 
include altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like 
activity. With JCAR017, to date, the start of neurologic symptoms has been noted between 3 to 
23 days (median 10 days) (Abramson, 2017) after CAR T cell infusion and in severe cases may 
require admission to the intensive care unit (ICU) for frequent monitoring, respiratory support, or 
intubation for airway protection. The symptoms are variable and generally occur as CRS is 
resolving or after CRS resolution. 
4.1. 
Pathophysiology of Neurologic Toxicities 
The pathogenesis of neurotoxicity is poorly defined. Analysis of a subset of subjects treated with 
JCAR017 (study 017001 – TRANSCEND NHL001) with NHL who have high baseline tumor 
burden (measured by the sum of product of the perpendicular diameters or high serum LDH 
(≥ 500 U/L) prior to the start of lymphodepletion) also have a higher risk for developing 
neurotoxicity (Siddiqi, 2017). In addition, severe neurotoxicity has also been reported in subjects 
with B-cell ALL and higher disease burden at the time of CD19 directed CAR T cell infusion 
(Park, 2017; Gust, 2017). 
Peak levels of IL-6, IFN-γ, ferritin, and CRP are significantly higher in subjects who develop any 
Grade or Grade 3 or higher neurotoxicity (Turtle, 2016; Heipel, 2017). Protein levels in the 
cerebrospinal fluid (CSF) are usually elevated in patients with neurotoxicity, compared with 
baseline measurements, suggesting disruption of the blood-brain barrier. Other organ dysfunction 
(hepatic and renal), as well as hypoxemia, and infection, might also contribute to the 
encephalopathy (Neelapu, 2018). In another study, it has been reported that evidence for 
cytokine-mediated endothelial activation causes coagulopathy, capillary leak, and blood-brain 
barrier disruption allowing transit of high concentrations of systemic cytokines into the CSF 
(Gust, 2017). 
4.2. 
Clinical Management of Neurologic Toxicities 
The optimal management of CAR T cell-induced neurotoxicity is unknown at this time. These 
management guidelines represent the current state of knowledge and additional information will 
be provided to Investigators as it becomes available. Management should also be guided as per 
institutional or standard clinical practice, and as determined by the Investigator or treating 
physician and/or consulting neurologist. A thorough neurologic evaluation, including 
electroencephalogram (EEG), magnetic resonance imaging (MRI) or computer tomography (CT) 
scan of the brain and diagnostic lumbar puncture and frequent monitoring of cognitive function 
(eg, mini mental status exams or handwriting tests) should be considered. 
Treatable causes of neurologic dysfunction, such as infection or hemorrhage should be ruled out. 
Common manifestations of neurotoxicity (eg, confusion, seizure, aphasia), can also be seen with 
infection, electrolyte imbalances, metabolic acidosis, uremia, concomitant medication use (eg, 
narcotics), and other medical conditions. Other causes for such symptoms should be considered. 
Magnetic resonance imaging and CT scans of the brain are usually negative for any anatomical 
pathology that would account for the neurotoxicity symptoms observed in subjects treated with 
CAR T cell therapy, although rare cases of reversible T2/fluid attenuated inversion recovery 


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(FLAIR) MRI hyperintensity involving the thalami, dorsal pons, and medulla, and cerebral 
edema have been reported (Neelapu, 2018). 
For subjects who have neurologic toxicity in the presence of CRS, the CRS should be managed 
following the guidelines provided in Figure 1. 
Neurotoxicity should be evaluated following the guidelines provided in Figure 2. For concurrent 
CRS and neurotoxicity, the most aggressive intervention recommended by either guideline 
should be employed (if the recommendations for steroid doses differ, use the highest dose and/or 
frequency). For subjects with Grade 4 neurotoxicity with cerebral edema, high-dose 
corticosteroids, hyperventilation and hyperosmolar therapy has been recommended (Neelapu, 
2018). 
Note: Tocilizumab is not recommended for the treatment of neurotoxicity related to CAR T cell 
therapy, unless CRS or MAS/HLH is also present. Results from 2 studies, one of preemptive use 
of tocilizumab shortly after anti-CD19 CAR T cell therapy in relapsed/refractory NHL subjects 
(Locke, 2017), and the other mandatory use of tocilizumab at first fever (> 38.5 °C) in pediatric 
ALL patients treated with anti-CD19 CAR T cells (Gardner, 2017), demonstrated that early 
tocilizumab use either increased overall neurotoxicity and Grade ≥ 3 neurotoxicity rates (85% vs 
62% overall; 35% vs 26% Grade ≥ 3) or provided no improvement in neurotoxicity rates, 
respectively. These findings support the hypothesis that tocilizumab does not improve and may 
worsen isolated neurotoxicity (Locke, 2017). 
Neurotoxicity management guidelines are provided in Figure 2. 


 
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Figure 2: Neurotoxicity Treatment Algorithm 
 
 
Abbreviations: CAR = chimeric antigen receptor; CRS = cytokine release syndrome; CT = computed tomography; EEG = electroencephalogram; ICU = 
intensive care unit; LP = lumbar puncture; MRI = magnetic resonance imaging; NT = neurotoxicity; q = every. 
 
 
 
 
 
 
 
 
 
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5. REFERENCES 
Abramson JS, Palomba ML, Gordon LI, Lunning MA, Arnason JE, Wang M, et al. High durable 
CR rates in relapsed/refractory (r/r) aggressive B-NHL treated with the CD19-directed CAR T 
cell product JCAR017 (TRANSCEND NHL 001): defined composition allows for dose-finding 
and definition of pivotal cohort. Blood. 2017 Dec 7;130(1): Abstract. 
Actemra® [Prescribing Information]. South San Francisco, USA: Genentech Inc; 2013. 
Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125276s092lbl.pdf 
Benedetti FD, Brogan P, Grom A, Quartier P, Schneider R, De Graaf K, et al. OP0204 
Emapalumab, an interferon gamma (IFN-Y) blocking monoclonal antibody, in patients with 
macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis 
(SJIA). Annals of Rheumatic Diseases. 2019;78:178. 
Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and 
management. Blood. 2016 ;127(26):3321-30. 
Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al. Efficacy and toxicity 
management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl 
Med. 2014 Feb 19;6(224):224-5. 
Frey N. Cytokine release syndrome: Who is at risk and how to treat. Best Pract Res Clin 
Haematol. 2017 Dec;30(4):336-40. 
Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat 
leukemia remission by CD19 CAR T cells of defined formulation and dose in children and 
young adults. Blood. 2017;129(25):3322-31. 
Gust J, Hay KA, Hanafi LA, Li D, Myerson D, Gonzalez-Cuyar LF, et al. Endothelial activation 
and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 
CAR-T cells. Cancer Discov. 2017 Dec;7(12):1404-1419. 
Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, et al. Kinetics and biomarkers of 
severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. 
Blood. 2017 Nov 23;130(21):2295-306. 
Heipel M, Smith J, Brown W, Karimi M, Xie B, Li D, et al. Pharmacokinetic, pharmacodynamic 
and blood analytes associated with clinical response and safety in relapsed/refractory aggressive 
B-NHL patients treated with JCAR017. Blood. 2017 December 7, 2017;130(Suppl 1):2835. 
Karakike E, Giamarellos-Bourboulis EJ. Macrophage activation-like syndrome: A distinct entity 
leading to early death in sepsis. Front Immunol. 2019 Jan 31;10:55. 
Lehmberg K, Nichols KE, Henter JI, Girschikofsky M, Greenwood T, Jordan M, et al. 
Consensus recommendations for the diagnosis and management of hemophagocytic 
lymphohistiocytosis associated with malignancies. Haematologica. 2015 Aug;100(8):997-1004. 
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 Jul 10;124(2):188-95. 


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Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT 
Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with 
Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-38. 
Locke, FL, Neelapu SS, Bartlett NL, Lekakis LJ, Jabobson CA, Braunschweig I, et al. 
Preliminary results of prophylactic tocilizumab after axicabtagene ciloleucel (axi-cel; KTE-C19) 
treatment for patients with refractory, aggressive non-Hodgkin lymphoma (NHL). Blood. 2017 
Dec 7;130(1): Abstract 1547. 
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene 
ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 
28;377(26):2531-44. 
Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen 
receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 
Jan;15,(1):47-62. 
Park JH. Managing Cytokine Release Syndrome. Clinical Care Options Oncology [Internet]. 
2017; https://www.clinicaloptions.com/Oncology/Treatment Updates/Managing 
AEs/Modules/Managing_CRS.aspx. 
Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X, et al. Adult 
haemophagocytic syndrome. Lancet. 2014 Apr 26;383(9927):1503-1516. Erratum in: Lancet. 
2014 Apr 26;383(9927):1464. 
RoActemra® [Summary of Product Characteristics]. Welwyn Garden City, United Kingdom: 
Roche Products Limited; 2019. Available from: 
https://www.medicines.org.uk/emc/medicine/22311/SPC/RoActemra+20mg+ml+Concentrate+fo 
r+Solution+for+Infusion. 
Siddiqi T, Abramson JS, Li D, Brown W, Devries T, Dave K, et al. Patient characteristics and 
pre-infusion biomarkers of inflammation correlate with clinical outcomes after treatment with 
the defined composition, CD19-targeted CAR T cell product, JCAR017. Blood. 2017; 130(1): 
Abstract 193. 
Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR–T cells 
of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 
2016;126(6):2123-38. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Celgene Signing Page 
This is a representation of an electronic record that was signed electronically in Livelink. 
This page is the manifestation of the electronic signature(s) used in compliance with 
the organizations electronic signature policies and procedures. 
 
 
 
Date: Friday, 13 August 2021, 09:26 AM Eastern Daylight Time 
Meaning: Approved, no changes necessary. 
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CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or 
consultant for review by you, your staff, and ethics committee/institutional review 
board. The information contained in this document is regarded as confidential 
and, except to the extent necessary to obtain informed consent, may not be 
disclosed to another party unless such disclosure is required by law or regulations. 
Persons to whom the information is disclosed must be informed that the 
information is confidential and may not be further disclosed by them. 
 
– SUMMARY OF CHANGES – 
AMENDMENT NO. 5 
A PHASE 2, SINGLE-ARM, MULTI-COHORT, MULTI- 
CENTER TRIAL TO DETERMINE THE EFFICACY AND 
SAFETY OF JCAR017 IN ADULT SUBJECTS WITH 
AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA 
(TRANSCEND WORLD) 
INVESTIGATIONAL PRODUCT (IP): 
JCAR017 
PROTOCOL NUMBER: 
JCAR017-BCM-001 
ORIGINAL DATE: 
24 Apr 2017 
AMENDMENT No. 1 DATE: 
08 Jan 2018 
AMENDMENT No. 2 DATE: 
28 Dec 2018 
AMENDMENT No. 3 DATE: 
21 Nov 2019 
AMENDMENT No. 4 DATE: 
16 Nov 2020 
AMENDMENT No. 5 DATE: 
12 Aug 2021 
EudraCT NUMBER: 
2017-000106-38 
IND NUMBER: 
Not applicable 
 
Contact Information: 
Name: 
Title: 
Address: Route de Perreux 1, 2017 Boudry, Switzerland 
Phone: 
E-mail: 
 


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CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
 
 
{See appended electronic signature page} 
Signature of Celgene Therapeutic Area Head 
dd mmm yyyy 
Printed Name of Celgene Therapeutic Area Head and Title 
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable. 


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1. 
JUSTIFICATION FOR AMENDMENT 
Significant changes included in this amendment are summarized below: 
 
• Cohort 2 sample size was modified from a maximum of 28 to approximately 28 subjects 
The change made to the Cohort 2 sample size allows for additional flexibility in the number of 
subjects included in the study to account for potential dropout of subjects during the pre- 
treatment phase. 
Revised sections: Figure 1, Overall Study Design, Section 9.3.2, Cohort 2 
• Specified that Cohort 2 will have formal hypothesis testing at the time of the primary 
analysis 
a formal hypothesis testing will be performed on Cohort 
2 instead of on the pooled analysis from JCAR017-BCM-001 Cohort 2 and Study 017006 
[PILOT] combined. 
Revised sections: Section 9.1, Overview, Section 9.3.2, Cohort 2 
• Cohort 2 primary analysis will be triggered when approximately 28 subjects treated 
with JCAR017 have been followed for at least 6 months 
the timing of the primary efficacy analysis was amended 
to occur after approximately 28 treated subjects have been followed for at least 6 months after 
first response. 
Revised section: Section 9.3.2, Cohort 2 
• Reference rate for null hypothesis testing for Cohort 2 will be estimated from a Real- 
World Study 
The reference rate to be used for the null hypothesis testing for Cohort 2 will be generated from a 
retrospective patient-level Real-World data synthetic cohort better matching the population to be 
enrolled in the current study when compared to estimate from literature. 
Revised section: Section 9.3.2, Cohort 2 
• Cohort 5 inclusion criteria were amended to allow for enrollment of subjects who failed 
to proceed to HDCT and ASCT following induction therapy 
Study population in Cohort 5 was expanded to include subjects intended for transplant but who 
failed to proceed due to insufficient response at time of induction completion or due to failure of 
PBSC mobilization, given the poor prognosis and unmet medical need in these patients. 
Revised sections: Protocol Summary, Section 3.1, Study Design, Section 4.2, Inclusion Criteria 
• Timing of cohort 7 analysis was added 
Cohort 7 analysis will be performed after all subjects have been followed for at least 6 months. 
Revised section: Section 9.3.4, Cohort 7 


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• Requirement that no more than 1 subject per week treated at a given site was removed 
Gating was removed given all participating sites have now gained sufficient experience with 
CAR-T products and CAR-T administration is becoming routine procedure at participating 
BCM-001 study sites. 
Revised sections: Protocol Summary, Section 3.1, Study Design 
• Updated SAE reporting requirement for clonal outgrowth or monoclonality from 
vector site insertion 
Requirement to report clonal outgrowth or monoclonality from vector site insertion as an SAE 
was removed because the occurrence of clonal outgrowth will not result in a malignancy. All 
subjects will be closely monitored for signs of malignancy 
. In the event of an SPM, a sample of the neoplastic tissue will be requested for 
causality analysis related to use of integrating vector to determine if insertional oncogenesis is 
suspected. 
Revised sections: Section 6.4.10, Persistent Vector Sequence Monitoring, Section 10.2.1, 
Seriousness, 10.8.1.14, New Malignancies 
The amendment also includes other minor clarifications and corrections: 
• Added wording on approved CD19-directed CAR T therapies 
Revised Section: Section 1.2.2, CD19-targeted Chimeric Antigen Receptors 
• Updated Table 4, Table of Events 
o Footnote ll was added to clarify timing of brain magnetic resonance imaging (MRI) 
Revised section: Table 4, Table of Events 
• Clarified timing of CSF assessment for subjects enrolled in Cohort 5 
Revised sections: Protocol Summary, Table 4, Table of Events, Section 6.1.4, Pretreatment 
Evaluation, Section 6.2.7, Days 15, 22, and 29 (±2 days), Section 6.4.5, Cerebrospinal Fluid 
Assessment and Central Nervous System Symptom Assessment, Section 6.5, Efficacy 
Assessment 
• Timing of interactions between the sponsor and the sites was updated from weekly to at least 
monthly 
Revised Section: 3.1, Study Design 
• Added wording regarding alternate administration methods of MMSE in case of exceptional 
circumstances 
Revised sections: Table 4, Table of Events, Section 6.4.4, Routine Neurologic and Mini 
Mental State Examinations 
• Clarified that an autopsy tissue sample will be collected when there is a safety 
concern 
Revised section: Section 6.3.4, Assessments at Time of Death 


JCAR017 
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• Added wording regarding the statistical test to be used for hypothesis testing of the primary 
endpoint 
Revised Section: Section 9.6.2, Primary Endpoint 
• Updated Study Monitoring and Source Data Verification guidelines 
Revised Section: Section 15.1, Study Monitoring and Source Data Verification 
• Updated references 
Revised Section: Section 17, References 
• Update of abbreviations 
Revised Section: Appendix A, Table of Abbreviations 
 
Additional spelling, style, formatting corrections and minor editorial revisions were made 
throughout the document. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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JCAR017-BCM-001 Amendment 4.0: 16 Nov 2020 
EDMS Doc. Number: 25163136 - 22388469 
 
 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations. 
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them. 
 
– SUMMARY OF CHANGES – 
AMENDMENT NO. 4 
A PHASE 2, SINGLE-ARM, MULTI-COHORT, MULTI- 
CENTER TRIAL TO DETERMINE THE EFFICACY AND 
SAFETY OF JCAR017 IN ADULT SUBJECTS WITH 
AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA 
(TRANSCEND WORLD) 
INVESTIGATIONAL PRODUCT (IP): 
JCAR017 
PROTOCOL NUMBER: 
JCAR017-BCM-001 
ORIGINAL DATE: 
24 Apr 2017 
AMENDMENT No. 1 DATE: 
08 Jan 2018 
AMENDMENT No. 2 DATE: 
28 Dec 2018 
AMENDMENT No. 3 DATE: 
21 Nov 2019 
AMENDMENT No. 4 DATE: 
16 Nov 2020 
EudraCT NUMBER: 
2017-000106-38 
IND NUMBER: 
Not applicable 
 
Contact Information: 
Name: 
Title: 
Address: Route de Perreux 1, 2017 Boudry, Switzerland 
Phone: 
E-mail: 
 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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JCAR017-BCM-001 Amendment 4.0: 16 Nov 2020 
EDMS Doc. Number: 25163136 - 22388469 
 
 
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
 
 
{See appended electronic signature page} 
Signature of Celgene Therapeutic Area Head 
dd mmm yyyy 
Printed Name of Celgene Therapeutic Area Head and Title 
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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JCAR017-BCM-001 Amendment 4.0: 16 Nov 2020 
EDMS Doc. Number: 25163136 - 22388469 
 
 
1. 
JUSTIFICATION FOR AMENDMENT 
Significant changes included in this amendment are summarized below: 
 
• Cohort 2 sample size was modified from N=28 to a maximum of 28 subjects to be 
treated with JCAR017 
The hypothesis-testing primary analysis will be based on a sample size of 80 subjects pooled 
from Cohort 2 of this study and Study 017006 (PILOT) enrolling a population in the United 
States (US) that mirrors the population treated in Cohort 2. The change made to the Cohort 2 
sample size allows for flexibility in the number of subjects included from each study. 
Revised sections: Figure 1, Overall Study Design, Section 9.3.2, Cohort 2 
• Specified that the primary analysis for Cohort 2 will be descriptive without formal 
hypothesis testing 
Cohort 2 primary analysis (N= max 28) will be descriptive only. A formal hypothesis testing will 
be performed on the pooled analysis set (JCAR017-BCM-001 Cohort 2 and Study 017006 
[PILOT]) which comprises 80 evaluable subjects across both studies. 
Revised section: Section 9.3.2, Cohort 2 
• Clarified that the pooled analysis from Cohort 2 and Study 017006 (PILOT) will be 
reported outside of the JCAR017-BCM-001 Clinical Study Report (CSR) 
Since data from JCAR017-BCM-001 Cohort 2 will be pooled with data from Study 017006 
(PILOT), the details of the pooled analysis will be presented in a separate statistical analysis plan 
(SAP) and the results of this analysis reported outside of the JCAR017-BCM-001 CSR. 
Revised section: Section 9.3.2, Cohort 2 
• Cohort 2 descriptive analysis will be triggered when the last subject treated with 
JCAR017 has been followed for at least one post-baseline efficacy assessment 
instead of 6 months 
The Cohort 2 descriptive analysis will be performed when a total of 80 evaluable subjects across 
Cohort 2 and Study 017006 (PILOT) have been followed for at least one post-baseline efficacy 
assessment. This allows to reliably assess the primary endpoint of overall response rate (ORR). 
Duration of response will be evaluated and updated at a later time point. 
Revised section: Section 9.3.2, Cohort 2 
• Updates on required screening, baseline and post-baseline evaluations for primary 
central nervous system lymphoma(PCNSL) (Cohort 5) subjects were provided to 
align with standardized baseline evaluations according to Abrey, 2005 It was 
clarified that an ophthalmologic evaluation is required at screening for subjects with 
PCNSL (Cohort 5) to exclude ocular lymphoma infiltration and does not need to be 
repeated thereafter unless symptoms occur. Cerebrospinal fluid does not need to be 
repeated if negative at screening, unless to confirm disease progression. 
Revised sections: Protocol Summary, Table 4, Table of Events, Section 4.2, Inclusion Criteria, 
Section 6.1.1, Screening , Section 6.1.4 Pretreatment Evaluation (following enrollment and 


JCAR017 
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JCAR017-BCM-001 Amendment 4.0: 16 Nov 2020 
EDMS Doc. Number: 25163136 - 22388469 
 
 
within 7 days prior to lymphodepleting chemotherapy), Section 6.2.7, Days 15, 22, and 29 (±2 
days), 6.3, Post-Treatment Period (Follow-up), Section 6.3.1, Unscheduled Evaluations, Section 
6.5, Efficacy Assessment 
• Inclusion criterion #8 was added back for subjects with non-Hodgkin lymphoma 
(NHL) 
“For subjects with NHL (except Cohort 5): Subjects must have positron emission 
tomography (PET)-positive disease as per Lugano Classification (Cheson, 2014)”This 
inclusion criterion was added back, correcting an error at time of last amendment. Instead of 
only removing the reference to subjects with Richter’s transformation, the whole inclusion 
criterion had been deleted. In the previous protocol amendment, inclusion criterion #8 had 
been entirely removed, including for subjects with NHL while all subjects enrolled - except 
Cohort 5 (PCNSL) - must have positron emission tomography (PET)-positive disease as per 
Lugano Classification (Cheson, 2014). 
Revised section: Section 4.2, Inclusion criteria 
The amendment also includes other minor clarifications and corrections: 
• 
 
Revised section: MEDICAL MONITOR AND EMERGENCY CONTACT 
INFORMATION 
• The length of enrollment period has been extended from 24 to 40 monthsRevised 
sections: Protocol Summary, Section 3.3, Study Duration for SubjectsUpdated Figure 
1, Overall Study Design 
Revised section: Figure 1, Overall Study Design 
• Inclusion criterion #9 has been updated to clarify required evaluations for PCNSL 
subjects 
Revised section: Section 4.2, Inclusion Criteria 
• Clarification that restaging for Cohort 4 subjects is mandatory after 2 cycles of 
induction to check for a complete metabolic responseRevised section: Table 4, Table 
of Events (footnote k), Section 6.1.4, PretreatmentUpdated Table 4, Table of Events 
− peripheral blood sample (hematology) collection at D60 was added 
− Collection timepoints for peripheral blood samples for biomarkers (peripheral 
blood mononuclear cell (PBMC) and immunophenotyping) were split into 2 
separate lines. 
− Footnote k and hh were updated 
− Footnote jj was added for computed tomography (CT)/magnetic resonance 
imaging (MRI) at Day 90/120 
− Footnote kk was added 
Revised section: Table 4, Table of Events 


JCAR017 
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JCAR017-BCM-001 Amendment 4.0: 16 Nov 2020 
EDMS Doc. Number: 25163136 - 22388469 
 
 
• Updated Table 5 to clarify that bridging radiation therapy is not allowed for Cohort 5 
subjects 
Revised section: Table 5, Washout Periods Prior to Leukapheresis and Prior to 
Lymphodepleting Chemotherapy 
• Updated wording on required biomarkers assessments at different study visits for 
clarity. 
Revised sections: Section 6.1.2, Leukapheresis, Section 6.1.4, Pretreatment 
evaluation, Section 6.2.2, JCAR017 Administration: Day 1, Section 6.2.4, Day 4 (+1 
day), Section 6.2.5, Day 8 (±1 day), Section 6.2.6, day 11 (±1 day), Section 6.2.7, 
Days 15, 22, and 29 (±2 days), Section 6.3, Post-Treatment Period (Follow-up) 
• Added peripheral blood sample (hematology) required on Month 2 
Revised sections: Section 6.3, Post-Treatment Period (Follow-up), Table 4, Table of 
Events 
• Added ophthalmologic examination among the list of unscheduled evaluations 
Revised section: Section 6.3.1, Unscheduled Evaluations 
• Clarified language regarding performing and capturing immune effector cell- 
associated encephalopathy (ICE) scores coupled with other neurological assessments 
Revised sections: Table 4, Table of Events, Section 6.1.4, Pretreatment Evaluation, 
Section 6.2.2, JCAR017 Administration: Day 1, Section 6.2.4, Day 4 (+1 day), 
Section 6.2.5, Day 8 (±1 day), Section 6.2.7, Days 15, 22, and 29 (±2 days), Section 
6.3, 
Post-Treatment Period (Follow-up), Section 6.3.1, Unscheduled Evaluations, 
Section 6.4.4, Routine Neurologic and Mini Mental State Examinations, Section 9.7, 
Safety AnalysisProvided clarification on the method of calculation of the viral copy 
number (VCN) per cell 
Revised section: Section 6.4.10, Viral Vector Sequence Pharmacokinetic Testing 
• Clarified that the Enrolled-set will include all subjects that pass eligibility criteria at 
screening 
Revised Section: Section 9.2.2, Enrolled Set 
• Definition of outpatient subjects was added 
Revised section: Section 9.3.4, Cohort 7 
• Clarified that the primary efficacy endpoint for Cohort 4, and 5 will be ORR as 
determined by Investigator assessment 
Revised section: Section 9.6.2, Primary Endpoint 
• Changes to subgroup analyses: 
− Added additional subgroup analysis of prior response status: refractory or 
relapsed within 12 months to last therapy versus relapsed ≥12 months to last prior 
therapy 


JCAR017 
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EDMS Doc. Number: 25163136 - 22388469 
 
 
− Clarified that additional age categories per cohorts are defined in the study SAP 
− Clarified that for all subgroup analyses age and Central Nervous System (CNS) 
disease status at screening will be considered 
Revised section: Section 9.6.4, Subgroup Analyses 
• Update of abbreviations 
Revised Section: Appendix A, Table of Abbreviations 
 
Additional spelling, style, formatting corrections and minor editorial revisions were made 
throughout the document. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 51.0 
1 
JCAR017-BCM-001 Amendment 3: 21 Nov 2019 
EDMS Doc. Number: 24268861 - 22388469 
 
 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations. 
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them. 
 
– SUMMARY OF CHANGES – 
AMENDMENT NO. 3 
A PHASE 2, SINGLE-ARM, MULTI-COHORT, MULTI- 
CENTER TRIAL TO DETERMINE THE EFFICACY AND 
SAFETY OF JCAR017 IN ADULT SUBJECTS WITH 
AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA 
(TRANSCEND WORLD) 
INVESTIGATIONAL PRODUCT (IP): 
JCAR017 
PROTOCOL NUMBER: 
JCAR017-BCM-001 
ORIGINAL DATE: 
24 Apr 2017 
AMENDMENT No. 1 DATE: 
08 Jan 2018 
AMENDMENT No. 2 DATE: 
28 Dec 2018 
AMENDMENT No. 3 DATE: 
21 Nov 2019 
EudraCT NUMBER: 
2017-000106-38 
IND NUMBER: 
Not applicable 
 
Contact Information: 
Name: 
Title: 
Address: Route de Perreux 1, 2017 Boudry, Switzerland 
Phone: 
E-mail: 
 
 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 51.0 
2 
JCAR017-BCM-001 Amendment 3: 21 Nov 2019 
EDMS Doc. Number: 24268861 - 22388469 
 
 
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
 
 
{See appended electronic signature page} 
Signature of Celgene Therapeutic Area Head 
dd mmm yyyy 
Printed Name of Celgene Therapeutic Area Head and Title 
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 51.0 
3 
JCAR017-BCM-001 Amendment 3: 21 Nov 2019 
EDMS Doc. Number: 24268861 - 22388469 
 
 
1. 
JUSTIFICATION FOR AMENDMENT 
Significant changes included in this amendment are summarized below: 
• Cohort 4 (High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 
rearrangements with diffuse large B-cell lymphoma [DLBCL] histology) clarified to 
allow consolidation after first line therapy 
The protocol was updated to clarify that enrolled subjects in Cohort 4 will proceed with 
JCAR017 infusion after first line therapy including anthracycline and rituximab (or other CD20- 
targeted agent) containing regimen. First line therapy is considered as induction prior to 
JCAR017 consolidation. Subjects with complete metabolic response after 2 cycles of induction 
will proceed with JCAR017 infusion only at time of relapse, if applicable. 
The rationale for this change is to explore JCAR017 in this high-risk patient population to better 
address this high unmet medical need. 
To align with new 2016 World Health Organization (WHO) classification, the double hit 
lymphoma (DHL)/triple hit lymphoma (THL) terminology was changed to WHO nomenclature 
for this population: High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 
rearrangements with DLBCL histology (HGBL). 
Revised Sections: Protocol Summary; Section 1.1, Disease Background; Section 3.1, Study 
Design; Figure 1, Overall Study Design; Section 4.2, Inclusion Criteria #6; Section 9.3.5, Gated 
Cohorts 
• Cohort 5 (Primary Central Nervous System Lymphoma) modified to second line 
population 
With the recent change in the treatment paradigm with high dose chemotherapy and autologous 
stem cell transplant (ASCT) as the new standard of care in first line, the second line patient 
population has become the true unmet medical need. 
The protocol was updated to restrict the enrollment to the second line population after failure of 
first line therapy with high-dose chemotherapy and ASCT. 
To allow for closer disease monitoring, the efficacy response assessment schedule was updated 
to bimonthly response assessments for the first 6 months. 
It was specified that prior whole brain radiotherapy clarification is not allowed for subjects 
enrolled in Cohort 5. 
Revised Sections: Protocol Summary; Section 3.1, Study Design; Figure 1, Overall Study 
Design; Section 4.2, Inclusion Criteria #6; Section 4.3, Exclusion Criteria #16; Table 4, Table of 
Events; Section 6.3, Post-Treatment Period (Follow-up) 
• Cohort 6 (Richter’s transformation) removed 
Preliminary data from ongoing trials suggests that subjects with Richter’s transformation may 
not optimally benefit from chimeric antigen receptor (CAR) T therapy alone and may benefit 
from novel combinations. Therefore, Cohort 6 has been removed from the protocol. 
Revised Sections: Protocol Summary; Table 1, Study Objectives; Table 2, Study Endpoints; 
Section 3.1, Study Design; Figure 1, Overall Study Design; Section 4.2, Inclusion Criteria #6 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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and #8; Table 4, Table of Events; Section 6.1, Pretreatment Period; Section 6.2, Treatment 
Period; Section 6.3, Post-Treatment Period (Follow-up); Table 6, Exploratory Biomarkers 
Sampling; Section 9.3.5, Gated Cohorts; Section 9.6.3, Secondary Efficacy Endpoints; Section 
9.9.3, Exploratory Analysis 
• Addition of Cohort 7 (Outpatient) 
A favorable benefit/risk profile of JCAR017 and preliminary outpatient data in ongoing 
JCAR017 clinical trials in the United States (US) has shown outpatient administration to not 
compromise safety in carefully selected subjects. Cohort 7 was added to explore the benefit/risk 
profile of JCAR017 outpatient treatment in Europe. 
Subjects meeting eligibility criteria for Cohort 1 and suitable for monitoring as outpatients will 
be enrolled in Cohort 7. These subjects must meet the conditions outlined in the Outpatient 
Administration and Monitoring Guidance for Lisocabtagene Maraleucel. 
The primary objective of Cohort 7 is to evaluate the safety of JCAR017 treatment in subjects 
intended to be treated as outpatients. Safety monitoring boundaries based on Bayesian 
framework have been added to the stopping rules for Cohort 7 (Table 3). The secondary 
objective of Cohort 7 is to determine the efficacy, defined as overall response rate (ORR) of 
JCAR017 in subjects intended to be treated as outpatients. The primary and secondary objectives 
of the study have been updated accordingly. 
Revised Sections: Protocol Summary; Table 1, Study Objectives; Table 2, Study Endpoints; 
Section 3.1, Study Design; Figure 1, Overall Study Design; Section 3.2.2, Criteria for Pausing or 
Stopping Cohort 7; Table 3, Safety Monitoring Boundaries Based on Thall and Simon; Section 
4.2, Inclusion Criteria #6; Section 9.3.4, Cohort 7; Table 8, Example Rates (± 95% Confidence 
Intervals); Section 9.6.2, Primary Endpoint; Section 9.6.3, Secondary Efficacy Endpoints 
• Criteria for Pausing or Stopping the Study 
The criteria for automatically pausing the study were removed from Section 3.2.1 of the protocol 
since existing data from over 300 subjects (including 33 adult subjects treated in Europe) have 
shown a tolerable and manageable safety profile, and the Data Safety Monitoring Board (DSMB) 
review data across all JCAR017 studies on an ongoing basis. Should a significant safety or 
efficacy issue be identified, all Investigators will be notified immediately and the DSMB will be 
convened in an expedited fashion to make a recommendation as to the future conduct of the 
study. 
Revised Section: Section 3.2.1 Criteria for Pausing or Stopping the Study 
• Patient interviews 
- 
For subjects enrolled under Protocol Amendment 3, patient interviews will be reduced to 
Pretreatment Evaluation, Day 90, and Day 270 
Already collected interviews allow valuable conclusions on the short-term impact of treatment. 
Additional data to assess long-term and longitudinal impact is still needed. To reduce burden on 
subjects, 8 timepoints were removed for subjects enrolled under Protocol Amendment 3 (ie, 
Pretreatment evaluation, D1, D29, D60, D180, D365, D545, and D730). 
Revised Section: Table 7, Table of Events, Patient Interviews 


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EDMS Doc. Number: 24268861 - 22388469 
 
 
Thus, the exclusion criteria have been revised to only 
• Inclusion criteria and Pregnancy risk updated with information on blood and organ 
donation, contraception and breastfeeding following exposure to lymphodepletion, 
combination agent and/or JCAR017 
There are no exposure data to provide a recommendation concerning duration of contraception 
following treatment with JCAR017. The JCAR017 program excludes pregnant subjects from 
participation and mandates that subjects use highly effective contraception. So far, no pregnancy 
has occurred in the JCAR017 clinical development program. No animal studies have been 
conducted with JCAR017 to assess whether it could cause fetal harm when administered to a 
pregnant woman. It is not known whether JCAR017 has the potential to be transferred to the 
fetus via the placenta and cause fetal toxicity, including B-cell lymphocytopenia. As the risk for 
the mother and fetus or newborn is unknown at this time, and negative CAR T quantitative 
polymerase chain reaction (qPCR) tests do not reliably predict complete disappearance of CAR 
T cells from the body, this test cannot be used to guide duration of contraception. Therefore, the 
indication that contraception may be changed or breastfeeding may be resumed following two 
subsequent negative CAR T qPCR tests was removed from the inclusion criteria. 
Revised Sections: Section 4.2, Inclusion Criteria #12, #13, and #14; Section 10.4, Pregnancy 
• Removal of the deep venous thrombosis (DVT) / pulmonary embolism (PE) / 
anticoagulation and vascular tumor invasion exclusion criteria as well as statements 
regarding stable disease/anticoagulation to be added to the Lymphodepleting 
Chemotherapy and Criteria for JCAR017 Treatment sections of the protocol. 
The following exclusion criteria have been revised to read as follows: 
- 
Tumor invasion of venous or arterial vesselsProgressive vascular tumor invasion, 
thrombosis, or embolism 
- 
Deep venous thrombosis (DVT) or pulmonary embolism (PE) within 3 months of 
leukapheresis and/or DVT or PE that requires ongoing therapeutic levels of 
anticoagulationVenous thrombosis or embolism not managed on a stable regimen of 
anticoagulation 
 
exclude patients with venous thrombosis or embolism not managed on a stable regimen of 
anticoagulation or patients with progressive vascular tumor invasion, thrombosis, or embolism. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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EDMS Doc. Number: 24268861 - 22388469 
 
 
Revised Sections: Section 4.3, Exclusion Criteria #17 and #18; Section 6.2.2, JCAR017 
Administration: Day 1 
• Addition of 2 exclusion criteria 
- 
Known severe hypersensitivity to dimethyl sulfoxide (DMSO) or Dextran 
- 
Systemic immunostimulatory agents (including but not limited to interferon and 
interleukin [IL]-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior 
to JCAR017 infusion. 
Revised Section: Section 4.3, Exclusion Criteria #16 and #18 
• Update of study number of subjects 
As a result of Cohort 6 removal and Cohort 7 addition, the study number of subjects was 
updated. 
Revised Sections: Protocol Summary; Section 3.1, Study Design; Figure 1, Overall Study 
Design; Section 4.1, Number of Subjects 
• New conditions to be reported as serious adverse events (SAEs) 
New incidence or exacerbation of a pre-existing neurologic disorder, a prior rheumatologic or 
other autoimmune disorder and new incidence of a hematologic disorder, will be reported 
irrespective of causality as SAEs. 
Revised Section: Table 9, Recording Periods for Adverse Events 
 
The amendment also includes several other minor clarifications and corrections: 
• Update of protocol product deviation plan language 
Revised Sections: Section 7.3.5, Protocol Product Deviation Plan; Section 7.3.6, Exception Use 
of Non-conforming Product 
• Addition of Mini Mental State Examination (MMSE) performed on a daily basis in 
case of Neurotoxicity 
Revised Sections: Table 4, Table of Events, footnote hh; Section 6.2.2, Treatment Period; Section 
6.3, Post-Treatment Period (Follow-up); Section 6.4.4, Routine Neurologic and Mini Mental 
State Examinations 
• Modifications of washout periods prior to lymphodepleting chemotherapy 
Revised Section: Table 5, Washout Periods Prior to Leukapheresis (and Prior to 
Lymphodepleting Chemotherapy) 
• Pharmacokinetic (PK) analysis population split by qPCR and by flow cytometry 
(previously combined) 
Revised Sections: Table 1, Study Objectives; Table 2, Study Endpoints; Section 9.2.6, qPCR 
Pharmacokinetic Analysis Set; Section 9.2.7, Flow Cytometry Pharmacokinetic Analysis Set; 
9.6.3, Secondary Efficacy Endpoints; Section 9.9.3, Exploratory Analysis 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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EDMS Doc. Number: 24268861 - 22388469 
 
 
• Updated wording in Section 9.3.3 Cohort 3 (Japan only) 
In Japan, the analysis will be conducted by combining Cohorts 1, 2 and 3. The primary efficacy 
analysis will be performed after at least 10 Japanese subjects in Cohort 3 have been treated with 
JCAR017 conforming product and have been followed for at least 3 months or until death, 
progressive disease, or withdrawal from study, and at the time when the number of the subjects 
who are eligible for the Efficacy Evaluable Set has reached at least 34 subjects in total of 
Cohorts 1, 2 and 3. The primary efficacy analysis and safety analysis will be based on JCAR017- 
Treated Set (all subjects who have received JCAR017 conforming product). 
Revised Sections: Section 9.3.3 Cohort 3 (Japan only) 
• European Organisation for Research and Treatment of Cancer – Quality of Life 
C30 (EORTC QLQ-C30) subscales split between secondary objectives/endpoints 
and exploratory objectives/endpoints 
Revised Sections: Protocol Summary; Table 1, Study Objectives; Table 2, Study Endpoints 
• European Quality of Life – 5 Dimensions Health State Classifier to 5 Levels (EQ- 
5D-5L) moved from secondary objectives/endpoints to exploratory 
objectives/endpoints 
Revised Sections: Protocol Summary; Table 1, Study Objectives; Table 2, Study Endpoints 
• Functional Assessment of Cancer Therapy – Lymphoma “Additional concerns” 
subscale (FACT-LymS) specified throughout the Amendment 
Revised Sections: Protocol Summary; Table 1, Study Objectives; Table 2, Study Endpoints; 
Section 6.8.3, FACT-LymS 
• Removal of saliva sample collection as biomarker for pharmacogenomics 
Revised Sections: Section 6.1, Pretreatment Period; Table 6, Exploratory Biomarkers Sampling 
• Clarification of health-related quality of life sections 
Revised Sections: Table 1, Study Objectives; Table 2, Study Endpoints 
• Clarification of biomarker sections 
Revised Sections: Table 1, Study Objectives; Table 2, Study Endpoints; Section 9.9.3, 
Exploratory Analysis 
• Reordering of the pregnancy wording applicable for female and male 
Revised Section: Section 10.4, Pregnancy 
• Diffusion capacity of carbon monoxide (DLCO) adjusted with Dinakara equation 
Revised Sections: Protocol Summary; Section 3.1, Study Design; Section 4.2, Inclusion Criteria 
#6; Section 6.1.1, Screening; Appendix G, hematopoietic cell transplantation (HCT)-specific 
comorbidity index (HCT-CI) Score Calculator. 
• Clarification of hepatitis exclusion criteria 
Revised Section: Section 4.3, Exclusion Criteria #8 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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Confidential and Proprietary 
Approved v 51.0 
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JCAR017-BCM-001 Amendment 3: 21 Nov 2019 
EDMS Doc. Number: 24268861 - 22388469 
 
 
• Hospital resource utilization listed in exploratory endpoints and added to the table 
of events 
Revised Sections: Table 2, Study Endpoints; Table 4, Table of Events 
• Removal of the detection of replication-competent lentivirus from exploratory 
endpoint since already included in safety endpoint 
Revised Section: Table 2, Study Endpoints 
• Clarification of prohibited concomitant medications 
Revised Section: 8.2, Prohibited Concomitant Medications and Procedures 
• Clarification of viral vector sequence pharmacokinetic testing 
Revised Sections: Section 6.4.10, Viral Vector Sequence Pharmacokinetic Testing 
• Clarification of management of toxicities associated with JCAR017 
Revised Sections: Section 10.8, Potential Risks and Management of Treatment Toxicities; 
Appendix M, JCAR017 Management guidelines for cytokine release syndrome and neurologic 
toxicities (V3.01) 
• Clarification regarding clinical stability before LDC and JCAR017 
Revised Section: Section 6.2, Treatment Period; 6.2.1, Lymphodepleting Chemotherapy (start 5 
to 10 days prior to JCAR017 infusion) 
• The study product doses are written at ten to the power of six (instead of eight) 
Revised Sections: Protocol Summary; Section 1.2.4., Clinical Experience with JCAR017 and 
Related CAR T Cell Products; Section 1.3.1, Study Rationale and Purpose; Section 1.3.2, 
Lymphodepleting Chemotherapy Rationale; Section 1.3.3, Rationale for JCAR017 Dose 
Selection; Section 3.1, Study Design; Figure 1, Overall Study Design; Section 7.3.4, JCAR017 
Administration 
• Update of references 
Revised Section: Section 17, References 
• Update of Appendix M 
Revised Section: Appendix M, JCAR017 management guidelines for cytokine release syndrome 
and neurologic toxicities 
• Update of abbreviations 
Revised Section: Appendix A, Table of abbreviations 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 31.0 
1 
JCAR017-BCM-001 Amendment 2 Final: 28 Dec 2018 
EDMS Doc. Number: 23246110 - 22388469 
 
 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations. 
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them. 
 
– SUMMARY OF CHANGES – 
AMENDMENT NO. 2 
A PHASE 2, SINGLE-ARM, MULTI-COHORT, MULTI- 
CENTER TRIAL TO DETERMINE THE EFFICACY AND 
SAFETY OF JCAR017 IN ADULT SUBJECTS WITH 
AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA 
 
INVESTIGATIONAL PRODUCT (IP): 
JCAR017 
PROTOCOL NUMBER: 
JCAR017-BCM-001 
ORIGINAL DATE: 
24 Apr 2017 
AMENDMENT No. 1 DATE: 
8 Jan 2018 
AMENDMENT No. 2 DATE: 
28 Dec 2018 
EudraCT NUMBER: 
2017-000106-38 
IND NUMBER: 
Not applicable 
 
 
Contact Information: 
Name: 
Title: 
Address: Route de Perreux 1, 2017 Boudry, Switzerland 
Phone: 
E-mail: 
 
 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 31.0 
2 
JCAR017-BCM-001 Amendment 2 Final: 28 Dec 2018 
EDMS Doc. Number: 23246110 - 22388469 
 
 
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
 
 
{See appended electronic signature page} 
Signature of Celgene Therapeutic Area Head 
dd mmm yyyy 
Printed Name of Celgene Therapeutic Area Head and Title 
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 31.0 
3 
JCAR017-BCM-001 Amendment 2 Final: 28 Dec 2018 
EDMS Doc. Number: 23246110 - 22388469 
 
 
1. 
JUSTIFICATION FOR AMENDMENT 
Significant changes included in this amendment are summarized below: 
• Safety: Inclusion of subjects with Eastern Cooperative Oncology Group (ECOG) 
performance status was restricted to ECOG 0-1, unless otherwise specified (Section 
4.2) 
 
“Inclusion criterion 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 
1 (Cohort 1, 4, 5 or 6). Subjects not eligible for transplants (TNE) with ECOG performance 
status 0, 1 or 2 may be enrolled in Cohort 2 or 3 only, if they meet all other inclusion/exclusion 
criteria.” 
• Safety: Subjects with vascular tumor invasion will not be eligible 
 
“Exclusion criterion 17. Tumor invasion of venous or arterial vessels” 
Revised Section: Section 4.3. 
• Safety: Subjects with deep venous thrombosis (DVT) and/or pulmonary embolism 
(PE) will not be eligible 
As additional measure, subjects with deep venous thrombosis (DVT) and/or 
pulmonary embolism (PE) will not be eligible. 
“Exclusion criterion 18. Deep venous thrombosis (DVT)/pulmonary embolism (PE) within 3 
months of ICF signature and/or DVT/PE that requires ongoing therapeutic levels of anti- 
coagulation.” 
Revised Section: Section 4.3. 
• A note was added for selection of subjects with central nervous system (CNS) 
involvement 
Clarification on the selection of subjects with primary or secondary CNS involvement must 
consider risk factors for severe adverse events and alternative treatment options. Subjects should 
only be enrolled if the potential benefit outweighs the risk for the subject, as considered by the 
Investigator 
“Note: Subjects with secondary central nervous system (CNS) lymphoma involvement may enroll 
in Cohorts 1 to 4 and 6; subjects with primary central nervous system lymphoma (PCNSL) are 
eligible for Cohort 5. Subject selection must consider clinical risk factors for severe adverse 
events (AEs) and alternative treatment options. Subjects should only be enrolled if the 
Investigator considers the potential benefit outweighs the risk for the subject.” 
Revised Sections: Protocol Summary, Section 3.1, and Section 4.2. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 31.0 
4 
JCAR017-BCM-001 Amendment 2 Final: 28 Dec 2018 
EDMS Doc. Number: 23246110 - 22388469 
 
 
• Safety: Subjects must be clinically stable prior to receiving JCAR017 infusion 
Treating physicians must evaluate a subject’s medical condition to assess recovery from prior 
toxicities and exclude significant worsening in clinical status when compared to initial eligibility 
criteria at time of LD chemotherapy and of JCAR017 infusion. 
“Subjects must be clinically stable and must have recovered from prior toxicities, to receive LD 
chemotherapy and proceed to JCAR017 infusion. Neither LD chemotherapy nor JCAR017 
treatment should be administered if there is a worsening of performance status to ECOG 2, rapid 
clinical deterioration, or evidence of rapidly progressive disease. Note: subjects who are 
transplant not eligible may have ECOG 2 however must be clinically stable, recover from prior 
toxicities, and not have evidence of rapidly progressive disease or rapid clinical deterioration 
prior to receiving LD chemotherapy or JCAR017 infusion.” 
Revised Section: Protocol Summary. 
• Safety: Pre-infusion criteria evaluation of subject’s clinical status was added prior 
to receiving JCAR017 infusion as an additional safety measure. 
An added safety evaluation of subject’s clinical status (e.g. ECOG status, rapid deterioration 
and rapid progression) must be performed prior to JCAR017 infusion. A pre-infusion criteria 
check was added for treating physicians to determine that subjects are not experiencing any 
significant worsening of their clinical status as compared to initial eligibility criteria. 
“Subjects should not experience a significant worsening in clinical status compared to initial 
eligibility criteria that would, in the opinion of the treating physician, increase the risk of adverse 
events associated with JCAR017 infusion. Subjects who meet at least one of the following 
criteria on the day of scheduled JCAR017 infusion should have JCAR017 administration 
delayed: 
• Suspected or active systemic infection 
• Onset of fever ≥ 38°C/100.4°F, not related to underlying disease 
• Presence of progressive radiographic abnormalities on chest x-ray, or requirement for 
supplemental oxygen to keep saturation greater than 91% 
• Cardiac arrhythmia not controlled with medical management 
• Hypotension requiring vasopressor support 
• New-onset or worsening of other non-hematologic organ dysfunction ≥ Grade 3 
• Taking any of the prohibited medications as described in Section 8.2 
Subjects with active infection must have JCAR017 infusion postponed until the active infection 
has resolved (subjects with suspected/ active infection must have negative culture for at least 24 
hours on appropriate antibiotics or negative rapid viral panel). Subjects with organ toxicities 
may not receive JCAR017 until the organ toxicities have recovered to ≤ Grade 2. In case of 
delayed infusion, lymphodepleting chemotherapy may need to be repeated after discussion with 
the Sponsor (see Section 6.2.1). 
In the event that a subject experiences any of the above, the Sponsor must be contacted and 
discussion regarding delay of treatment must occur.” 
Revised Sections: Section 6.2.2. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 31.0 
5 
JCAR017-BCM-001 Amendment 2 Final: 28 Dec 2018 
EDMS Doc. Number: 23246110 - 22388469 
 
 
The amendment also includes several other minor clarifications and corrections: 
• Editorial changes. – Protocol Summary, Section 1.3.1. 
• Clarification for subjects with transformed disease to have at least 2 lines of systemic 
therapy for his/her transformed disease (i.e. DLBCL) for Cohort 1 and 1 line for 
Cohort 2 to be eligible. – Protocol Summary, Section 3.1, Section 4.2. 
• Clarification to continue enrollment in Cohort 1 without gating after safety and 
feasibility are met per safety evaluation of the first three subjects. – Protocol 
Summary and Section 3.1. 
• The formal interim analysis has been removed from Cohort 2 as data from the 017006 
Pilot study will become available sooner and results will be pooled across both trials 
– Protocol Summary, Section 9.3.2, and Figure 1. 
• Instead of the formal interim analysis, added an early safety assessment performed 28 
days after JCAR017 is administered to the 10th subject treated in Cohort 2. This was 
introduced to ensure subject safety as subject with ECOG2 remain eligible in this 
Cohort. – Protocol Summary, Section 3.1, and Figure 1. 
• Specified measurement of pharmacokinetic (PK) profiles of JCAR017 in peripheral 
blood by qPCR detection for JCAR017 vector sequence (secondary objective) and by 
flow cytometry (exploratory objective). – Section 2, Table 2, Table 3, and Table 5. 
• Added evaluation of MRD of underlying CLL in subjects with Richter’s 
transformation (Cohort 6). – Section 2, Table 2, Table 3, Section 6.3.1, Section 6.7.2, 
Table 5, and Section 9.9.3. 
• Revised timeframe for overall survival (OS) to be assessed up to last subject last visit 
instead of up to 2 years after JCAR017 infusion. – Table 2. 
• Additional language to specify as consistent with Reference Safety Information (RSI) 
in the Investigator Brochure (IB), all life-threatening or fatal events will be 
considered unexpected for purpose of reporting SUSARs to regulatory authorities and 
will be reported in expedited fashion if considered related to JCAR017. – Section 
3.2.1. 
• Added evaluation of MRD of underlying CLL in subjects with Richter’s 
transformation (Cohort 6). – Section 2, Table 3, Section 6.3.1, Section 6.7.2, Table 5, 
and Section 9.9.3. 
• Clarification on histological confirmation of diagnosis at last relapse if subject did not 
experience complete response (CR), then the most recent tumor biopsy will be 
considered adequate. For subjects with PCNSL, corresponding pathology report is 
required if archival tumor material is not available and repeated biopsy is not feasible. 
– Section 4.2, and Table 3. 
• Erroneous superscript ‘*’ removed. – Section 4.2. 
• Superscript ‘**’ updated to superscript ‘*’. – Section 4.2. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 31.0 
6 
JCAR017-BCM-001 Amendment 2 Final: 28 Dec 2018 
EDMS Doc. Number: 23246110 - 22388469 
 
 
• Specified additional types of non-invasive malignancies listed in Exclusion criterion 
5. – Section 4.3. 
• Exclusion criterion 13 revised to include cerebral edema and remove paresis – 
Section 4.3. 
• Exclusion criterion 16 added dose for lymphotoxic chemotherapeutic agent, 
cyclophosphamide > 300 mg/m2. – Section 4.3. 
• Revisions to the visit windows at Screening and Follow-up visits (Days 60, 90, 180, 
270, 365, 545, and 730 and Survival). Frequency of Survival Follow-up was also 
updated to every 3 months. – Table 3 and Section 6.3. 
• Addition and clarification of brain magnetic resonance imaging (MRI) and cerebral 
spinal fluid (CSF) assessment at screening are for subjects with suspected or 
confirmed CNS involvement; and subsequent assessments are only for subjects with 
confirmed CNS involvement. – Table 3, Section 6.1.1, Section 6.1.4, Section 6.2.7, 
Section 6.3, Section 6.4.5, Section 6.5. 
• Specified to repeat CSF until subject reaches complete response, then obtain 
subsequent CSF assessment only if suspected of CNS relapse. – Table 3, Section 6.3, 
and Section 6.4.5. 
• Removal of an exploratory optional assessment (tumor biopsy) for restaging if subject 
received anticancer therapy at pre-treatment evaluation. –Table 3, Section 6.1.4, 
Table 5. 
• Updated the washout periods prior to leukapheresis and prior to lymphodepleting 
(LD) chemotherapy. – Table 4. 
• Specified criteria to assess the subject prior to receiving LD chemotherapy. – Section 
6.1.4. 
• Revised the recommended administration of LD chemotherapy (fludarabine IV dose 
reduction percentage (%) is based on updated creatinine clearance [CrCl] ranges). – 
Section 7.3.1. 
• Added language that it is acceptable to use another H1 antihistamine as a JCAR017 
premedication, in case diphenhydramine hydrochloride is not available. – Section 
7.3.2. 
• Clarification on the monitoring of vital signs. – Table 3, Section 6.2.2, and Section 
7.3.4. 
• Updated list of medications that should be reported during inpatient and Intensive 
Care Unit (ICU) stays, and list of prohibited medications during treatment and 
follow-up periods. – Section 8.1. 
• Language was added for sites to have tocilizumab readily available prior to JCAR017 
administration as required for treatment and management of Cytokine Release 
Syndrome (CRS). – Section 8.3. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene Corporation 
Confidential and Proprietary 
Approved v 31.0 
7 
JCAR017-BCM-001 Amendment 2 Final: 28 Dec 2018 
EDMS Doc. Number: 23246110 - 22388469 
 
 
• Additional information provided on specific statistical analyses to be performed for 
Cohort 3 (Japan only). – Section 9.3.3. 
• Removed censoring wording for subjects receiving new anticancer therapy without 
progressive disease. – Section 9.6.3 
• Adverse reporting period was reformatted for clarity. – Section 10. 
• Added potential risks associated with cytopenias and infections. – Section 10.8.1. 
• Updated CRS and Neurotoxicities (NT) guidelines. – Appendix N 
• Misspellings, style and formatting. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
1 
Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
CONFIDENTIAL 
This protocol is provided to you as an Investigator, potential Investigator, or consultant for review by 
you, your staff, and ethics committee/institutional review board. The information contained in this 
document is regarded as confidential and, except to the extent necessary to obtain informed consent, 
may not be disclosed to another party unless such disclosure is required by law or regulations. 
Persons to whom the information is disclosed must be informed that the information is confidential 
and may not be further disclosed by them. 
 
– SUMMARY OF CHANGES – 
AMENDMENT NO. 1 
A PHASE 2, SINGLE-ARM, MULTI-COHORT, MULTI- 
CENTER TRIAL TO DETERMINE THE EFFICACY AND 
SAFETY OF JCAR017 IN ADULT SUBJECTS WITH 
AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA 
 
INVESTIGATIONAL PRODUCT (IP): 
JCAR017 
PROTOCOL NUMBER: 
JCAR017-BCM-001 
ORIGINAL DATE: 
24 Apr 2017 
AMENDMENT No. 1 DATE: 
8 Jan 2018 
EudraCT NUMBER: 
2017-000106-38 
IND NUMBER: 
Not applicable 
 
 
Contact Information: 
Name: 
Title: 
Address: Route de Perreux 1, 2017 Boudry, Switzerland 
Phone: 
E-mail: 
 
 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
2 
Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
CELGENE THERAPEUTIC AREA HEAD SIGNATURE PAGE 
 
 
{See appended electronic signature page} 
Signature of Celgene Therapeutic Area Head 
dd mmm yyyy 
Printed Name of Celgene Therapeutic Area Head and Title 
By my signature, I indicate I have reviewed this summary of changes and find its 
content to be acceptable. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
3 
Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
1. 
JUSTIFICATION FOR AMENDMENT 
 
Significant changes included in this amendment are summarized below: 
• Transformed indolent B-cell non-Hodgkin lymphoma (B-NHL) was restricted to 
transformed follicular lymphoma (tFL) 
Transformed indolent B-NHL was restricted to tFL in subjects with diffuse large B-cell 
lymphoma (DLBCL) not otherwise specified (NOS) to align the sudy population of cohort 1 with 
that TRANSCEND NHL 001 . 
 
 
Revised Sections: Protocol Summary, Section 3.1., Section 4.2. 
• Definition of transplant not eligible (TNE) subjects was revised 
, the definition of TNE subjects was revised 
and better defined to include those who are deemed ineligible for high-dose chemotherapy and 
HSCT due to age, performance status or comorbidity. At the very least, subjects have to meet 
one of the following criteria to be considered TNE: age ≥ 70 years, ECOG performance status ≥ 
2, impaired pulmonary function (DLCO ≤ 60%), impaired cardiac function (LVEF < 50%), 
impaired renal function (CrCl < 60 mL/min/1.73m2) or impaired hepatic function (AST/ALT > 
2x ULN, bilirubin > 2 mg/dL or cirrhosis Child-Pugh B or C. However, subjects must meet all 
protocol specified eligibility criteria to be deemed eligible for JCAR017 therapy. 
Subjects with prior hematopoietic stem cell transplant are not eligible for this cohort. 
The Frailty Score (Larocca, 2016) was added as a baseline assessment in this patient population. 
Revised Sections: Protocol Summary, Section 3.1., Section 4.2. 
• Eligibility criteria for Cohort 3 (Japan only) were revised 
Subjects for Cohort 3 (Japan only) must meet eligibility criteria for either Cohort 1 or 2. This 
change will allow for TNE subjects to be included in the Japan specific cohort. 
Revised Sections: Protocol Summary, Section 3.1., Section 4.2. 
• Eligibility criteria for Cohort 5 were revised 
Cohort 5 will include only subjects with primary central nervous system lymphoma (PCNSL) 
after ≥ 1 line of therapy instead of ≥ 2 lines of therapy. The prior line of therapy must have 
included high-dose methotrexate. 
In absence of effective treatment option and established standard of care (SOC) at time of first 
relapse, the protocol was updated to allow those subjects who have failed ≥ 1 line of therapy to 
be included. 
Revised Sections: Protocol Summary, Table 2, Section 3.1., Section 4.2., Table 3 
• Eligibility criteria for Cohort 6 were revised 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
4 
Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
Cohort 6 includes subjects after ≥ 1 line of therapy instead of ≥ 2 lines of therapy for Richter’s 
transformation. 
In absence of effective treatment option and established SOC at time of first relapse, the protocol 
was updated to allow those subjects who have failed ≥ 1 line of therapy to be included. 
Revised sections: Protocol Summary, Section 3.1., Section 4.2. 
• Safety run-in for Cohort 3 (Japan only) was added 
A similar safety run-in as for subjects treated in Europe (first three subjects treated with a 
minimum interval between JCAR017 infusions of 14 days and need for hospitalization of the 
first 10 subjects after JCAR017 infusion) was added for subjects treated in Japan. Cohort 3 was 
changed to enroll independently from the European cohorts. 
Revised Sections: Protocol Summary, Section 3.1. Section 6.2.2. 
• Inclusion criterion for subjects with secondary DLBCL CNS involvement was 
revised 
Based on preliminary results from the TRANSCEND NHL 001 study showing disease clearing 
in two subjects with secondary CNS infiltration without the occurrence of CNS toxicity, subjects 
with secondary DLBCL CNS involvement will be allowed in all but Cohort 5, which will focus 
on subjects with PCNSL only. 
Revised Sections: Protocol Summary, Section 4.2. 
The amendment also includes several other minor clarifications and corrections: 
• Added clarification to the secondary objectives to evaluate other measures of efficacy 
of JCAR017 . – Table 1, Protocol Summary. 
• Clarified that CAR+ T cell suspension will be provided as 2 individually formulated 
CD8+CAR+ and CD4+CAR + frozen T cell suspensions. – Protocol Summary, 
Section 1.2.3, Section 1.3.1. 
• Language for clinical experience from PLAT-02 study updated. – Section 1.2.4. 
• Latest clinical experience from TRANSCEND NHL 001 study as reported in the 
literature was added. – Section 1.2.4. 
• Latest data on JCAR017 dosing from TRANSCEND NHL 001 as reported in the 
literature was added.– Section 1.3.1. 
• Editorial changes. – Section 1.3.4. 
• Added secondary objective corresponding to secondary endpoint ORR in underlying 
chronic lymphocytic leukemia (CLL) in subjects with Richter’s transformation 
(Cohort 6) as per Table 2. – Protocol Summary, Table 1. 
• Addition of FACT-Lym “Additional concerns” subscale, Table 1, Table 2, Table 3, 
Section 6.1.1, Section 6.1.4, Section 6.2.2, Section 6.2.7., Section 6.3, Section 6.8, 
Section 6.8.3, Section 9.6.3, Appendix A. and Appendix L. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
5 
Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
• Pharmacokinetic (PK) profile of JCAR017 in bone marrow changed from mandatory 
to when sample available. –Table 1, Table 2, Table 3, Section 6.1.4, Section 6.2.7, 
Section 6.3.2, Section 6.6, Table 4. 
• PK profile of JCAR017 in bone marrow moved from secondary to exploratory 
objectives. – Protocol Summary, Table 1, Table 2. 
• Evaluation of immune and tumor cells in bone marrow biopsy changed from 
mandatory to when sample available and language related to collection of samples 
was amended. – Table 1, Table 3, Section 6.1.4, Section 6.2.7, Section 6.3.2, Table 4. 
• The exploratory safety endpoint, response and time to resolution for severe cytokine 
release syndrome (sCRS) and/or neurotoxicity interventions, was amended. – Table 2. 
• Language describing Cohort 4 was clarified in the following sections – Protocol 
Summary, Section 3.1, Section 4.2, and deleted from Section 6.1.2. 
• The option of retreatment with JCAR017 was removed. – Section 3.1, Section 6.3.3, 
Section 9.2.3. 
• Language describing the Long-term Follow-up (LTFU) study was amended. – 
Protocol Summary, Section 3.1, Section 6.3.7. 
• Clarification that the study enrollment will be paused if the safety and/or futility 
boundaries are crossed pending DSMB recommendations. – Section 3.2.1. 
• Figure 1 was updated with a new figure. – Figure 1. 
• Figure 2 was revised to reflect changes made in this amendment. – Figure 2. 
• Exclusion criterion 7 was added (subjects who have received previous CD19-targeted 
therapy). – Section 4.3. 
• Exclusion criterion 15 was revised (lenalidomide and ibrutinib are allowed if at least 
3 half-lives have elapsed prior to leukapheresis; graft-versus-host disease (GVHD) 
therapies was replaced by immunosuppressive therapies). Section 4.3. 
• Column for Survival Follow-Up was added. – Table 3. 
• Amendments were made to align the table and footnotes with changes in the body 
text. – Table 3. 
• Language was added to involve institutional decision boards in subject selections, 
where applicable. – Section 6.1.1. 
• Assessments applicable to TNE subjects in Cohorts 2 and 3 were clarified. – Table 3 
footnote x, Section 6.1.1. 
• Formal Neuropsychological Evaluation was removed and Table 3, Section 6.1.1., 
Section 6.1.4, Section 6.2.7, Section 6.3.6 and Section 10.7.3 edited accordingly. 
• Language for PET scan to confirm disease was clarified. – Table 3 footnotes m, n, 
and p, Section 6.1.1. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
6 
Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
• The requirement to complete patient diaries was removed. – Summary, Table 3, 
Section 6, Section 9.9.2, Section 14.1. 
• Patient interviews were removed from Table 3 and are detailed in a new schedule of 
patient interviews. – Table 3, Table 5, Section 6.8.3. 
• Patient interview on Day 29 added. – Section 6.2.7, Table 5. 
• Patient interview at leukapheresis added. – Section 6.1.2, Table 5. 
• Replication-competent lentivirus (RCL) testing at screening removed. – Table 3, 
Section 6.1.1. 
• Specified that PK by flow cytometry is not required at Japanese sites. Table 3 
footnote bb, Section 6.1.1, Section 6.2.2, Section 6.2.4, Section 6.2.5, Section 6.2.6, 
Section 6.2.7, Section 6.3, Section 6.3.1, Section 6.3.2, Section 6.6. 
• Anticancer treatments allowed between leukapheresis and lymphodepleting (LD) 
chemotherapy specified. – Section 6.1.3. 
• Clarified that subjects must meet pre-treatment eligibility criteria before initiation of 
LD chemotherapy. – Table 3 footnote y, Section 6.1.3, Section 6.1.4. 
• Specified that subjects with PCNSL must continue to have measurable disease per 
MRI after anticancer treatments between leukapheresis and LD chemotherapy. – 
Summary, Section 6.1.3. 
• Measurement of height at pre-treatment evaluation removed. – Table 3, Section 6.1.4. 
• Bone marrow aspirate and biopsy at pre-treatment evaluation, Day 15 and upon PD 
removed. – Table 3, Section 6.1.4, Section 6.2.7, Section 6.6, Section 6.3.2, Table 4. 
• Requirement to perform bone marrow aspirate and biopsy for subjects with previous 
bone marrow involvement upon achieving of a complete response added. – Table 3, 
Section 6.3.3. 
• Language regarding ongoing infections prior to LD chemotherapy removed because 
this is stated in Section 6.2.1. – Section 6.2.2. 
• All assessments performed on Days 2 and 3, except for vital signs, physical 
examination, and recording of AEs and concomitant medications, were removed. – 
Table 3, Section 6.2.3, Table 4 (soluble factors). 
• Language for assessments/procedures that are required after progressive disease 
(PD)/relapse and/or after subsequent anticancer treatment clarified. – Table 3 footnote 
b, Section 6.3. 
• Language for RCL sample collection and testing specified. – Table 3 footnote cc, 
Section 6 , Section 6.4.10. 
• Language for viral vector sequence PK by quantitative polymerase chain reaction 
(qPCR) sample collection and testing specified. – Table 3 footnotes w and cc, Section 
6.3, Section 6.4.11. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
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Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
• Reporting of adverse events (AE) and associated concomitant medications for 
subjects starting a new anticancer therapy after JCAR017 revised. – Table 3 footnotes 
b and dd, Section 6.3, Section 8.1, Section 10.1. 
• Requirement to collect blood and tissue sample collection in case an autopsy is 
performed and if feasible added. – Section 6.3.4. 
• Requirement to report any confirmed positive result from RCL testing as an SAE 
within 24 hours and to notify the relevant health authorities added and requirement to 
report any observations of clonal outgrowth or monoclonality as an SAE within 24 
hours.. – Section 6.4.10, Section 6.4.11, and Section 10.2.1. 
• Language regarding request for neoplastic tissue samples for RCL assessment at time 
of disease recurrence and new malignancy was clarified. – Section 6.4.10. 
• Specified that clinical management of study subjects will be based on local 
assessments. – Section 6.4.12. 
• Specified that MRD in subjects with Richter’s transformation will be assessed on 
peripheral blood until MRD negative result obtained which should be confirmed on 
bone marrow aspirate. – Protocol Summary, Section 6.5. 
• Definition of pseudoprogression was added. – Section 6.5.1 
• Language on biomarker assessments amended. – Section 6.7.2, Table 2, Table 4, 
Section 9.9.2. 
• Detailed description of European Organisation for Research and Treatment of Cancer 
– Quality of Life C30 (EORTC QLQ-C30) added and questionnaire appended. – 
Section 6.8.1, Appendix J. 
• Detailed description of European Quality of Life-5 Dimensions health state classifier 
to 5 Levels (EQ-5D-5L) added and questionnaire appended to protocol. – Section 
6.8.2. Appendix K. 
• Detailed description and schedule of patient interviews added. – Section 6.8.3, Table 
5. 
• Dosing of JCAR017 premedication specified. – Section 7.3.2, Section 8.3, Section 
10.7.5. 
• Reporting of AEs and associated concomitant medications for subjects receiving LD 
chemotherapy but no JCAR017 specified. – Table 3 footnote ee, Section 8.1, Section 
10.1. 
• Reporting of concomitant medications administered during hospitalizations specified. 
– Section 8.1. 
• sCRS removed as an indication for treatment with cetuximab. – Section 8.2. 
• Recommendation for prophylactic treatment for subjects at risk for tumor lysis 
syndrome added. – Section 8.3. 
• Details added on permitted concomitant medications. – Section 8.3. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
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Confidential and Proprietary 
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Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
• Definition of Efficacy Evaluable set added. – Section 9.2.4, Section 9.2.7, Section 
9.3.1, Section 9.3.2, Section 9.3.3, Section 9.3.4, Section 9.6.1. 
• Clarified that primary efficacy analysis will be based on the JCAR017-treated set and 
that the Enrolled set and Efficacy Evaluable set will be used for supportive analyses. 
– Section 9.2.7, Section 9.6.1. 
• Significance level for interim and primary analyses in Cohorts 1 and 2 specified. – 
Section 9.3.1, Section 9.3.2. 
• Cohorts 2 and 3 will not be gated. – Section 9.3.4 (formerly Section 9.3.2). 
• Aligned definition of overall response rate (ORR) and complete response (CR) rate 
with TRANSCEND NHL 001 study. – Section 9.6.2. 
• Clarified that subjects with unknown/missing response will be included in the 
analysis counted as non-responders applies to JCAR017-treated set and Enrolled set. 
– Section 9.6.2, Section 9.6.3. 
• Definition of duration of response clarified. – Section 9.6.3. 
• Language for exploratory biomarker analysis clarified. – Section 9.9.2. 
• AE reporting of manifestations of neurologic toxicities in the presence of cytokine 
release syndrome or alone specified. – Section 10.1. 
• Description of neurologic toxicities revised and toxicity management guidelines 
appended to protocol. – Section 10.7.3, Appendix N. 
• Link to Common Terminology Criteria for Adverse Events CTCAE removed. – 
Section 10.2.2. 
• Reporting of AE outcome revised. – Section 10.2.6. 
• Reporting of abnormal laboratory values clarified. – Section 10.3. 
• Reporting of progressive disease specified. – Section 10.5. 
• Reporting of death due to progressive disease revised. – Section 10.5.2. 
• Requirement to upload autopsy reports to the electronic data capture system removed. 
– Section 10.5.2. 
• Description of cytokine release syndrome was revised. Table 5 “Grading Criteria for 
CRS” and Table 6 “Cytokine Release Syndrome Treatment Algorithm” were 
removed and toxicity management guidelines appended to protocol. – Section 10.7.1, 
Appendix N. 
• Cairo-Bishop definition of laboratory tumor lysis syndrome added. – Section 10.7.6, 
Appendix M. 
• Manufacturing failure added as reason for treatment discontinuation. – Section 11.1. 
• Study termination by Sponsor added as reason for study discontinuation. – Section 
11.2. 


JCAR017 
Summary of Changes JCAR017-BCM-001 
Celgene 
Confidential and Proprietary 
9 
Protocol JCAR017-BCM-001 Amendment # 1 Final: 8 Jan 2018 
Approved v 21.0 
EDMS Doc. Number: 22388982 - 22388469 
 
 
• Clarified which clinical laboratory evaluations are to be performed locally and/or 
centrally. – Appendix F. 
• Alkaline phosphatase and ß2-microglobulin added to chemistry panel. – Appendix F. 
• Pregnancy (serum beta human chorionic gonadotropin [β-hCG]) moved from 
urinalysis to separate panel. – Appendix F. 
• Disease characterization was specified to histology, cell of origin, immunochemistry, 
cytogenetics, molecular sub-typing. – Appendix F. 
• Style and formatting 
• Based on revisions, references were added or deleted from Section 17 References 
Information.