A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Neoplasms, Neoplasms by Histologic Type, Lymphoproliferative Disorders, Lymphatic Diseases, Immunoproliferative Disorders, Immune System Disorder
Sponsor: Juno Therapeutics, a Subsidiary of Celgene

Protocol for 
 
Official Title of Study 
A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and 
Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient 
Setting (TRANSCEND-OUTREACH-007) 
NCT03744676 
March  17, 2020 

Approved
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
2
Protocol 017007 Amendment 2.0: 17 Mar 2020
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. 
Approved
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
3
Protocol 017007 Amendment 2.0: 17 Mar 2020
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.
Approved
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
4
Protocol 017007 Amendment 2.0: 17 Mar 2020
PROTOCOL SYNOPSIS
Protocol Number: 017007
Protocol Title: A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) 
B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)
Sponsor: Juno Therapeutics, Inc., a wholly-owned subsidiary of Celgene Corporation.
Study Rationale: 
JCAR017 is a CD19-directed genetically modified autologous T-cell immunotherapy consisting of a defined 
composition of chimeric antigen receptor (CAR) T-cell product with flat dosing of both CD4+CAR+ and 
CD8+CAR+ T-cell subsets. Clinical trials of JCAR017 and other CAR T-cell products to date have been 
performed in tertiary care centers that have consolidated the site of care for CAR T-cell administration and 
follow-up. In the US, however, about 80% of patients receiving treatment for relapsed or refractory (R/R) 
diffuse large B-cell lymphoma (DLBCL) in third line are treated outside of these centers. The product profile of 
JCAR017 is conducive to administration and monitoring in hospital outpatient clinics and cancer clinic 
networks; however, the safety profile of this product administered in nontertiary care centers has not been 
evaluated. Preliminary data from Juno Study 017001 show that treatment of this patient population with 
JCAR017 demonstrates encouraging efficacy results and a manageable safety profile, including low rates of 
severe cytokine release syndrome (CRS) and neurotoxicity (NT) events, which support outpatient administration 
and outpatient monitoring for toxicity. Early experience with JCAR017 in Study 017001 suggests that outpatient 
administration of JCAR017 can be provided safely with appropriate education and outpatient monitoring, and
can reduce the duration of inpatient hospital stays by 40% when compared to inpatient administration (Maloney 
2017). Thus, a safety study to assess the use of JCAR017 in nontertiary care outpatient settings is proposed to
confirm these initial findings. 
Study Objectives:
Primary:

To evaluate the safety of JCAR017 administered in nontertiary care centers as reflected by Grade ≥ 3 
adverse events (AEs) of CRS, NT, prolonged cytopenias, and infections in adult subjects with R/R
aggressive B-cell non-Hodgkin lymphoma (NHL)
Secondary:

To evaluate the overall safety and tolerability of JCAR017, including toxicity management and 
outcomes 

To evaluate the safety of JCAR017 treatment in subjects monitored as outpatients

To assess the antitumor activity of JCAR017

To assess the pharmacokinetic (PK) profile of JCAR017

To assess health-related quality of life (HRQoL) and health economics and outcome research (HEOR) 
Exploratory

 
Study Design: 
This is an open-label, multicenter, Phase 2 study to assess the safety and efficacy of JCAR017 administered in 
nontertiary care centers to adult subjects with R/R DLBCL, transformed DLBCL arising from indolent
histologies (tDLBCL),high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with 
DLBCL histology, primary mediastinal B-cell lymphoma (PMBCL) and follicular lymphoma Grade 3B. There 
will be no control group in this study.  
Approved
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
5
Protocol 017007 Amendment 2.0: 17 Mar 2020
Protocol Number: 017007
A total of 114 subjects may be enrolled to ensure that approximately 80 subjects are treated with JCAR017, with 
a minimum of approximately 50 treated subjects monitored as an outpatient.
Upon enrollment, subjects will undergo leukapheresis to obtain lymphocytes for JCAR017 product generation. 
While JCAR017 is being manufactured and if required to control their disease, subjects may receive salvage 
low-dose chemotherapy or 1 cycle of noncurative standard-of-care antitumor therapy (ie, bridging therapy).
Upon successful JCAR017 product generation, subjects will enter the treatment phase and will receive 
lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by JCAR017 at a dose 
of 100×106 CAR T cells administered intravenously (IV) 2 to 7 days after completion of lymphodepleting 
chemotherapy. 
After treatment with JCAR017, subjects will enter post-treatment follow-up, and will be followed on this study 
for up to 2 years for safety, PK and biomarkers, disease status, HRQoL, and survival, as described in more detail 
in the assessments sections below. Assessments for long-term safety, overall survival, and HRQoL will continue 
even after disease progression. After completing the 2 years of post-treatment follow-up in this protocol, long-
term follow-up (LTFU) for survival, long-term toxicity, and viral vector safety will continue under a separate 
protocol for up to 15 years following the last dose of JCAR017.
Oversight
A Safety Review Committee (SRC), comprised of Principal Investigators, and the Sponsor’s medical monitor, 
safety physician, and statistician will regularly assess the safety of JCAR017 administration throughout the trial. 
The SRC may make recommendations based on safety.
Study Population: 
The target study population consists of adult subjects with R/R aggressive B-cell NHL who have failed at least
2 prior therapies.
Inclusion Criteria:
Subjects must meet all of the following criteria to be enrolled in this study: 
1.
Age ≥ 18 years at the time of consent 
2.
Signed written informed consent prior to any study procedures 
3.
Relapsed or refractory B-cell NHL of the following histologies: 
DLBCL, not otherwise specified (NOS; includes biopsy-confirmed transformed DLBCL from indolent  
histologies), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with 
DLBCL histology, PMBCL and follicular lymphoma Grade 3B. Subjects must have been treated with 
an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease 
after at least 2 systemic lines of therapy for DLBCL or after autologous hematopoietic stem cell 
transplant (auto-HSCT). 
4.
Positron-emission tomography (PET)-positive disease according to the “Recommendations for Initial 
Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano 
Classification” 
5.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 
6.
Adequate organ function (must meet all), defined as: 
a.
Assessed by the Investigator to have adequate bone marrow function to receive lymphodepleting 
chemotherapy
b.
Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN), OR if greater than 1.5× ULN 
then calculated creatinine clearance (Cockcroft and Gault) > 30 mL/min 
c.
Alanine aminotransferase (ALT) ≤ 5 × 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) 
d.
Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events 
(CTCAE) Grade 1 dyspnea and oxygen saturation (SaO2) ≥ 92% on room air 
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
6
Protocol 017007 Amendment 2.0: 17 Mar 2020
Protocol Number: 017007
e.
Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed 
by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA) scan performed within
1 month of the determination of eligibility 
7.
Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line) 
8.
Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma 
confirmed on a biopsy since completing the prior CD19-targeted therapy 
9.
Females of childbearing potential* must:
a.
Have 2 negative pregnancy tests as verified by the Investigator (one negative serum beta-human 
chorionic gonadotropin [ß-hCG] pregnancy test result at screening, and within 48 hours prior to the 
first dose of lymphodepleting chemotherapy). This applies even if the subject practices true 
abstinence** from heterosexual contact.
b.
Either commit to true abstinence** from heterosexual contact or agree to use, and be able to 
comply with, effective contraception without interruption. Contraception methods must include 1
highly effective method from screening until at least 12 months after the lymphodepleting 
chemotherapy.
c.
Agree to abstain from breastfeeding during study participation and for at least 12 months following 
lymphodepleting chemotherapy. 
d.
There are 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.
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 highly effective 
and additional effective methods of contraception:

Intrauterine device (IUD)

Hormonal (birth control pill, injections, implants)

Tubal ligation 

Partner's vasectomy
10. Males who have partners of childbearing potential must:
a.
Practice true abstinence** or agree to use a condom during sexual contact with a pregnant female 
or a female of childbearing potential for 12 months after lymphodepleting chemotherapy even if he 
has undergone a successful vasectomy.
b.
There are 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.
* A female subjects of childbearing potential (FCBP) is a female who: 1) has achieved menarche at 
some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at 
least 12 consecutive months (ie, has had menses at any time in the preceding 12 consecutive months).
**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.
11. Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other 
individuals for at least 1 year following lymphodepletion chemotherapy. There are insufficient 
exposure data to provide any recommendation concerning the duration of refraining from tissue 
donation following treatment with JCAR017. Therefore, subjects treated with JCAR017 should not 
donate blood, organs, tissues, and cells for transplantation
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JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
7
Protocol 017007 Amendment 2.0: 17 Mar 2020
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from participation in this study:
1.
Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with 
secondary CNS involvement are allowed on study) 
2.
History of prior allogeneic hematopoietic stem cell transplant (allo-HSCT)
3.
Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or 
cladribine within 3 months of leukapheresis 
4.
History of another primary malignancy that has not been in remission for at least 2 years. The following 
are examples of exceptions from the 2-year limit: nonmelanoma skin cancer, definitively-treated stage 
1 solid tumor with a low risk of recurrence, curatively-treated localized prostate cancer, and cervical 
carcinoma in situ on biopsy or a squamous intraepithelial lesion on a Papanicolau smear
5.
Subjects with a history of or active human immunodeficiency virus (HIV) are excluded 
6.
Subjects with active hepatitis B, or active hepatitis C are also excluded. Subjects with a negative 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
7.
Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-
infection treatment at the time of leukapheresis or JCAR017 administration 
8.
Presence of acute or chronic graft-versus-host disease (GVHD) 
9.
History of any 1 of the following cardiovascular conditions within the past 6 months: Class III or IV 
heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial 
infarction, unstable angina, or other clinically significant cardiac disease
10. History or presence of clinically relevant CNS pathology such as epilepsy/seizure, paresis, aphasia, 
stroke, cerebral edema, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic 
brain syndrome, or psychosis 
11. Pregnant or nursing women. NOTE: Women of reproductive potential must have a negative serum 
pregnancy test performed within 48 hours of starting lymphodepleting chemotherapy 
12. Use of any of the following: 
a. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7
days prior to leukapheresis or 72 hours prior to JCAR017 administration. Physiologic replacement, 
topical, and inhaled steroids are permitted. 
b. Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤300 mg/m2) given after 
leukapheresis to maintain disease control must be stopped ≥7 days prior to lymphodepleting 
chemotherapy. 
c. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week 
of leukapheresis. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed 
if at least 3 half-lives have elapsed prior to leukapheresis. 
d. Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within
2 weeks of leukapheresis 
e. Experimental agents within 4 weeks of leukapheresis unless no response or disease progression is 
documented on the experimental therapy and at least 3 half-lives have elapsed prior to 
leukapheresis 
f.
Immunosuppressive therapies within 4 weeks of leukapheresis and JCAR017 administration (eg, 
calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, 
thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL6, or anti-IL6R) 
g. Donor lymphocyte infusions within 6 weeks of JCAR017 administration 
h. Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease (PD) in 
irradiated lesions or have additional nonirradiated, PET-positive lesions to be eligible. Radiation to 
a single lesion, if additional nonirradiated PET-positive lesions are present, is allowed up to
2 weeks prior to leukapheresis. 
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
8
Protocol 017007 Amendment 2.0: 17 Mar 2020
Protocol Number: 017007
13. Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not 
permit compliance with the protocol, as judged by the Investigator; or unwillingness or inability to 
follow the procedures required in the protocol 
14. Prior CAR T-cell or other genetically modified T-cell therapy 
15. Progressive vascular tumor invasion, thrombosis, or embolism 
16. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation 
Study Sites: Subjects will be enrolled at multiple sites in the United States.
Drug Product, Dose, and Mode of Administration: 
The JCAR017 drug product is a defined composition of autologous CD4+CAR+ and CD8+CAR+T cells that 
express a CD19-specific chimeric antigen receptor (CAR) and a truncated epidermal growth factor receptor 
(EGFRt) that are provided as frozen cell suspensions for IV administration at a flat dose. The JCAR017 drug 
product is provided as 2 individually formulated CD4+CAR+ and CD8+CAR+T-cell suspensions in media 
containing dimethyl sulfoxide for direct IV administration in equal CAR T-cell quantities.
JCAR017 is prepared at the site as 2 separate T-cell suspensions in syringes at doses of 50×106 CD8+CAR+ T 
cells and 50×106 CD4+CAR+ T cells (total dose of 100×106 CAR+ T cells) that are given IV in a single-dose 
schedule on Day 1 (between 2 and 7 days following the completion of lymphodepleting chemotherapy). 
Duration of Study and Subject Participation: 
The duration of study for each subject is up to 2 years, and the estimated total time for all subjects to complete 
the study is approximately
years.
Safety Assessments: 
Adverse events/serious AEs (SAEs) and laboratory abnormalities (type, frequency, and severity) will be 
collected. Adverse events of special interest (AESIs) may include, but are not limited to, cytokine release 
syndrome (CRS), neurological toxicity (NT), prolonged cytopenia, Grade ≥ 3 infection, tumor lysis syndrome
(TLS), macrophage activation syndrome (MAS), infusion reactions, and hypogammaglobulinemia, autoimmune 
disorder, and second primary malignancy (SPM).
Safety monitoring boundaries based on the incidence of Grade 3 or above JCAR017-related AESIs are
established using a Bayesian framework to help detect safety signals during the course of the study. If the safety 
boundaries are crossed, enrollment will be paused and an ad hoc SRC meeting will be held to review the data. 
The study will remain paused for enrollment pending the SRC’s recommendations. 
Efficacy Assessments: 
Tumor response will be assessed by diagnostic quality (with contrast) computed tomography (CT) scans (chest, 
neck, abdomen, and pelvis) and PET scans. Radiographic disease assessments will be performed pretreatment, at 
Day 29, and Months 3, 6, 9, 12, 18, and 24 months following the JCAR017 treatment or until disease 
progression. Bone marrow involvement by lymphoma will be assessed by PET scan only; bone marrow aspirates 
and biopsies will not be required for assessment of disease response. Disease response and duration will be 
assessed by the Investigators according to the “Recommendations for Initial Evaluation, Staging, and Response 
Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification” (Cheson 2014).
For subjects with suspected or confirmed CNS involvement, repeat cerebrospinal fluid (CSF) assessments by 
flow cytometry will be performed. 
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
10
Protocol 017007 Amendment 2.0: 17 Mar 2020
TABLE OF CONTENTS
TITLE PAGE..............................................................................................................................1
THERAPEUTIC AREA HEAD SIGNATURE PAGE ................................................................2
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE........................................................3
PROTOCOL SYNOPSIS............................................................................................................4
TABLE OF CONTENTS..........................................................................................................10
LIST OF ABBREVIATIONS....................................................................................................19
1.
INTRODUCTION..................................................................................................23
1.1.
B-cell Non-Hodgkin Lymphoma.............................................................................23
1.2.
CD19 as a Therapeutic Target.................................................................................24
1.3.
CD19-Targeted Chimeric Antigen Receptors..........................................................24
1.4.
JCAR017 Drug Product..........................................................................................25
1.5.
Clinical Experience with JCAR017.........................................................................25
2.
STUDY PURPOSE AND RATIONALE ................................................................26
2.1.
Rationale for JCAR017 Dose Level........................................................................26
2.2.
Rationale for Study Design.....................................................................................26
2.3.
Rationale for Lymphodepleting Chemotherapy.......................................................27
2.4.
Rationale for Endpoints ..........................................................................................27
2.5.
Risk/Benefit Summary............................................................................................27
3.
STUDY OBJECTIVES AND ENDPOINTS...........................................................28
4.
STUDY DESIGN AND INVESTIGATIONAL PLAN ...........................................30
4.1.
Overall Study Design..............................................................................................30
4.2.
Study Duration and Duration of Subject Participation.............................................31
4.3.
Study Completion...................................................................................................31
4.4.
Study Oversight......................................................................................................31
4.5.
Suspension or Early Termination of the Study ........................................................31
5.
STUDY POPULATION.........................................................................................32
5.1.
Inclusion Criteria....................................................................................................32
5.2.
Exclusion Criteria:..................................................................................................34
5.3.
Removal of Subjects from Treatment or Study........................................................35
5.3.1.
Screen Failures .......................................................................................................35
5.3.2.
Subject Discontinuation Prior to Receiving Study Treatment..................................36
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JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
11
Protocol 017007 Amendment 2.0: 17 Mar 2020
5.3.3.
Subject Discontinuation from Further Study Treatment...........................................36
5.3.4.
Subject Withdrawal from Study..............................................................................36
5.3.5.
Replacement of Study Subjects...............................................................................36
6.
STUDY TREATMENTS........................................................................................37
6.1.
Leukapheresis.........................................................................................................37
6.2.
Anticancer Treatments between Leukapheresis and Lymphodepleting 
Chemotherapy ........................................................................................................37
6.3.
JCAR017 Investigational Drug Product ..................................................................37
6.3.1.
Protocol Product Deviation Plan .............................................................................38
6.3.2.
Exception Use of Non-conforming Product.............................................................38
6.3.3.
Dose and Schedule..................................................................................................38
6.3.4.
Lymphodepleting Chemotherapy............................................................................38
6.3.5.
JCAR017 Premedication.........................................................................................39
6.3.6.
JCAR017 Preparation and Cell Thawing.................................................................39
6.3.7.
JCAR017 Administration........................................................................................39
6.3.8.
Acute Infusion Reactions........................................................................................40
6.4.
Recommended Supportive Care, Additional Treatment, and Monitoring.................40
6.5.
Concomitant Medications .......................................................................................40
6.5.1.
Medications Administered During Hospitalizations ................................................41
6.6.
Prohibited Medications...........................................................................................41
7.
POTENTIAL RISKS AND MANAGEMENT OF TOXICITIES............................42
7.1.
Cytokine Release Syndrome ...................................................................................42
7.2.
Fever ......................................................................................................................43
7.3.
Neurologic Toxicities .............................................................................................43
7.4.
Macrophage Activation Syndrome..........................................................................44
7.5.
Infusion Reactions ..................................................................................................44
7.6.
Tumor Lysis Syndrome ..........................................................................................45
7.7.
B-cell Aplasia.........................................................................................................45
7.8.
Cytopenias..............................................................................................................45
7.9.
Infections................................................................................................................45
7.10.
Graft-versus-host Disease .......................................................................................45
7.11.
Uncontrolled T Cell Proliferation............................................................................45
7.12.
Replication-competent Lentivirus, Clonality, and Insertional Oncogenesis .............46
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JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
12
Protocol 017007 Amendment 2.0: 17 Mar 2020
7.13.
Risks Associated with Lymphodepleting Chemotherapy.........................................46
8.
STUDY ASSESSMENTS AND PROCEDURES ...................................................46
8.1.
Schedule of Evaluations..........................................................................................47
8.2.
Study Visits ............................................................................................................47
8.2.1.
Screening (Approximately 1 to 2 Weeks Prior to Leukapheresis)............................47
8.2.2.
Optional Bridging Therapy for Disease Control Prior to Lymphodepleting 
Chemotherapy ........................................................................................................48
8.2.3.
Leukapheresis (Approximately 4 Weeks Prior to JCAR017 Administration)...........49
8.2.3.1.
Assessments Prior to Repeat Leukapheresis............................................................49
8.2.4.
Pretreatment Evaluation (Prior to Lymphodepleting Chemotherapy).......................50
8.2.5.
Lymphodepleting Chemotherapy Through Day 29..................................................51
8.2.5.1.
Criteria for Treatment .............................................................................................51
8.2.5.2.
Lymphodepleting Chemotherapy (Approximately 5 Days Prior to JCAR017).........51
8.2.5.3.
Criteria for JCAR017 Treatment.............................................................................52
8.2.5.4.
JCAR017 Administration–Day 1 (2 to 7 Days after Completion of the Last 
Dose of Lymphodepleting Chemotherapy)..............................................................53
8.2.5.5.
Day 2 through Day 29.............................................................................................54
8.2.6.
Follow-up Period: Through Month 24.....................................................................55
8.2.7.
Unscheduled Evaluations........................................................................................55
8.2.8.
Assessments on Disease Progression/Relapse .........................................................56
8.2.9.
Assessments in Subjects who Undergo Leukapheresis but Do Not Receive 
Treatment ...............................................................................................................57
8.2.10.
Long-term Follow-up..............................................................................................57
8.2.11.
Second Primary Malignancies Follow-up Period.....................................................57
8.3.
Study Assessments .................................................................................................57
8.3.1.
Efficacy Assessments .............................................................................................57
8.3.1.1.
Pseudoprogression..................................................................................................58
8.3.2.
Physical Examination .............................................................................................58
8.3.3.
Routine Neurological and Mini-Mental State Examinations....................................58
8.3.4.
Vital Signs..............................................................................................................58
8.3.5.
Tumor Biopsy.........................................................................................................58
8.3.6.
Adverse Events.......................................................................................................58
8.3.7.
Clinical Laboratory Evaluations..............................................................................58
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
13
Protocol 017007 Amendment 2.0: 17 Mar 2020
8.3.8.
ECOG Performance Status......................................................................................59
8.3.9.
MUGA/Echocardiogram.........................................................................................59
8.3.10.
Electrocardiogram ..................................................................................................59
8.3.11.
Cerebrospinal Fluid Examination and Central Nervous System Symptom 
Assessment.............................................................................................................59
8.3.12.
Pharmacokinetic, Pharmacodynamic, and Biomarker Assessments.........................60
8.3.12.1.
Pharmacokinetic Assessments.................................................................................60
8.3.12.2.
Viral Vector Sequence Testing ...............................................................................60
8.3.12.3.
Pharmacodynamic Assessments..............................................................................60
8.3.12.4.
8.3.12.5.
Immunogenicity Assessments.................................................................................61
8.3.12.6.
Replication-competent Lentivirus Testing...............................................................61
8.3.13.
Health-Related Quality of Life and Health Economics and Outcomes 
Research.................................................................................................................62
8.3.13.1.
EORTC QLQ-C30..................................................................................................62
8.3.13.2.
EQ-5D-5L ..............................................................................................................62
8.3.14.
Hospital Resource Utilization .................................................................................63
9.
SAFETY MONITORING AND REPORTING.......................................................63
9.1.
Definitions..............................................................................................................63
9.1.1.
Adverse Event ........................................................................................................63
9.1.2.
Serious Adverse Event............................................................................................63
9.1.3.
Adverse Events of Special Interest..........................................................................64
9.1.3.1.
Grading and Intensity of Adverse Events ................................................................64
9.2.
Relationship to Study Drug.....................................................................................65
9.3.
Recording Adverse Events......................................................................................65
9.3.1.
Recording a Diagnosis versus Signs and Symptoms................................................65
9.3.2.
Clinical Laboratory Abnormalities and Other Abnormal Assessments ....................66
9.3.3.
Recording Serious Adverse Events .........................................................................66
9.3.4.
Death Reports.........................................................................................................66
9.3.5.
Safety Queries ........................................................................................................66
9.3.6.
Pregnancy...............................................................................................................66
9.4.
Reporting Adverse Events to the Sponsor ...............................................................67
9.4.1.
Reporting Periods for AEs and SAEs......................................................................67
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9.4.2.
Reporting Timelines for Serious Adverse Events....................................................68
10.
STATISTICAL METHODS...................................................................................69
10.1.
General Considerations...........................................................................................69
10.2.
Analysis Sets ..........................................................................................................69
10.2.1.
Screened Set...........................................................................................................69
10.2.2.
Eligible Set.............................................................................................................69
10.2.3.
Leukapheresed Set..................................................................................................69
10.2.4.
JCAR017-treated Analysis Set................................................................................69
10.2.5.
Outpatient Analysis Set ..........................................................................................69
10.2.6.
Pharmacokinetic Analysis Set.................................................................................69
10.3.
Planned Analyses....................................................................................................69
10.3.1.
Subject Disposition and Baseline Characteristics ....................................................69
10.3.2.
Primary Endpoints..................................................................................................70
10.3.3.
Secondary Endpoints ..............................................................................................70
10.3.4.
Exploratory Endpoints............................................................................................71
10.3.5.
Safety Analysis.......................................................................................................71
10.3.5.1.
Adverse Events.......................................................................................................71
10.3.5.2.
Laboratory Data......................................................................................................71
10.3.5.3.
Safety Subgroup Analysis.......................................................................................72
10.3.5.4.
Safety Monitoring Boundaries ................................................................................72
10.3.6.
Efficacy Analysis....................................................................................................72
10.3.6.1.
Objective Response Rate ........................................................................................72
10.3.6.2.
Complete Response Rate ........................................................................................73
10.3.6.3.
Duration of Response .............................................................................................73
10.3.6.4.
Progression-free Survival........................................................................................73
10.3.6.5.
Overall Survival .....................................................................................................73
10.3.6.6.
Efficacy Subgroup Analysis....................................................................................73
10.3.7.
Pharmacokinetic Analyses ......................................................................................73
10.3.8.
Health-related Quality of Life and Health Economics and Outcomes 
Research.................................................................................................................74
10.3.9.
Nonconforming Product..........................................................................................74
10.4.
Sample Size Considerations....................................................................................74
10.5.
Timing of Analyses ................................................................................................75
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LIST OF TABLES
Table 1:
Study Objectives and Endpoints..............................................................................28
Table 2:
Reporting Periods for Concomitant Medications.....................................................40
Table 3:
Washout Periods Prior to Leukapheresis.................................................................49
Table 4:
Analytes for Clinical Laboratory Evaluations..........................................................59
Table 5:
Definitions of Serious Adverse Events....................................................................63
Table 6:
Special Considerations for SAE Reporting..............................................................64
Table 7:
Reporting Periods for AEs and SAEs......................................................................67
Table 8:
Example Rates (± 95% Confidence Intervals) .........................................................75
Table 9:
100
Table 10:
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LIST OF FIGURES
Figure 1:
Study Schema for Individual Subjects.....................................................................30
Figure 2:
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Figure 3:
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LIST OF ABBREVIATIONS
Abbreviation or Term
Definition/Explanation
AE
adverse event
AESI
adverse event of special interest
Allo-HSCT
allogeneic hematopoietic stem cell transplant
ASTCT
American Society for Transplantation and Cellular Therapy
AST
aspartate aminotransferase
AUC
area under the curve
Auto-HSCT
autologous hematopoietic stem cell transplant
ß-hCG
beta subunit of human chorionic gonadotropin
BCL2
B-cell lymphoma 2 gene 
BCL6
B-cell lymphoma 6 gene
BOR
best overall response
BR
bendamustine plus rituximab
CAR
chimeric antigen receptor
CBC
complete blood count
CFR
Code of Federal Regulations
CI
confidence interval
Cmax
maximum concentration
CNS
central nervous system
CR
complete response
CRA
clinical research associate
CRP
C-reactive protein
CRS
cytokine release syndrome
CSF
cerebrospinal fluid
CSR
clinical study report
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
DLBCL
diffuse large B-cell lymphoma
DMSO
dimethyl sulfoxide
DoCR
duration of complete response
DOR
duration of response
ECG
electrocardiogram
ECHO
echocardiogram
ECOG
Eastern Cooperative Oncology Group
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Abbreviation or Term
Definition/Explanation
eCRF
electronic case report form
EDC
electronic data capture
eGFR
estimated glomerular filtration rate 
EGFRt
truncated epidermal growth factor receptor
EORTC
European Organization for Research and Treatment of Cancer
EOS
End-of-Study
FDA
Food and Drug Administration
FFPE
formalin-fixed, paraffin-embedded
FiO2
fraction of inspired oxygen
flu/cy
fludarabine and cyclophosphamide
GCB
germinal center B cell
GCP
Good Clinical Practice
GFR
glomerular filtration rate
GM-CSF
granulocyte macrophage colony-stimulating factor
GVHD
graft versus host disease
HIV
human immunodeficiency virus
HLH
hemophagocytic lymphohistiocytosis
HRQoL
health-related quality of life
HSCT
hematopoietic stem cell transplant
IB
Investigator’s brochure
IBC
Institutional Biosafety Committee
ICF
informed consent form
ICH
International Council on Harmonisation
ICU
intensive care unit
IgA, IgG, or IgM
Immunoglobulin A, G, or M
IL-5, IL-6, or IL-10
Interleukin-5, 6, or 10
IL-6R
interleukin-6 receptor
IMID
immune modulating imide drug
IPI
International Prognostic Index
IRB
Institutional Review Board
IV
intravenous
IVIG
intravenous immunoglobulin
JCAR017
lisocabtagene maraleucel
LDH
lactate dehydrogenase
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Abbreviation or Term
Definition/Explanation
LN2
Liquid nitrogen
LTFU
long-term follow-up
LVEF
left ventricular ejection fraction
MAS
macrophage activation syndrome
MCL
mantle cell lymphoma
MedDRA
Medical Dictionary for Regulatory Activities
MRI
magnetic resonance imaging
MMSE
Mini-Mental State Examination
MUGA
multiple uptake gated acquisition scan
NHL
non-Hodgkin lymphoma
NOS
not otherwise specified
NT
neurotoxicity
OR
objective response
ORR
objective response rate
OS
overall survival
PBMC
peripheral blood mononuclear cell
PCR
polymerase chain reaction
PD
progressive disease
PET
positron emission tomography
PFS
progression-free survival
PK
pharmacokinetic(s)
PMBCL
primary mediastinal B-cell lymphoma
PPDP
Protocol Product Deviation Plan
PT
preferred term
qPCR
quantitative polymerase chain reaction
R-CEOP
rituximab plus cyclophosphamide, epirubicin, vincristine, and prednisone
R-CEPP
rituximab plus cyclophosphamide, etoposide, procarbazine, and prednisone
R-CHOP
rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone
R-Gem-Ox
rituximab with gemcitabine and oxaliplatin
RCL
replication-competent lentivirus
R-GDP
rituximab plus gemcitabine, cisplatin, and dexamethasone
R/R
relapsed or refractory
SAE
serious adverse event
SAP
Statistical Analysis Plan
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Abbreviation or Term
Definition/Explanation
SaO2
saturated oxygen
scFv
single chain variable fragment
sCRS
severe cytokine release syndrome
SD
stable disease
SOC
system organ class
SPD
sum of the perpendicular diameters
SPM
Second primary malignancy
SRC
Safety Review Committee
tDLBCL
transformed DLBCL from indolent histology
TEAE
treatment-emergent adverse event
TLS
tumor lysis syndrome
Tmax
time of maximum concentration
TMG
Toxicity management guidelines
TNF
tumor necrosis factor
ULN
upper limit of normal
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1.
INTRODUCTION
1.1.
B-cell Non-Hodgkin Lymphoma
Approximately 72,000 new cases of non-Hodgkin lymphoma (NHL) will be diagnosed and 
approximately 20,000 patients will die of their disease in the United States in 2019 (Siegel 
2019). NHL is the seventh most common cancer in the US, accounting for 4.2% of new cancers 
and 3.3% of all cancer-related deaths (SEER 2019). In the US, 80% to 85% of NHL cases are as 
B cell lymphomas and 15% to 20% are T-cell/natural killer cell lymphomas (NCCN 2019).
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive subtype, constituting 
approximately 30% of adult patients with NHL in the US, Europe, and Japan (Aoki 2008, Ferlay 
2013, Novelli 2013, NCCN 2019). DLBCL is a disease of the elderly, with a median age at 
diagnosis of approximately 70 years (Issa 2015, Smith 2015), although it may rarely occur in 
children and young adults. With current treatments, relapsed or refractory (R/R) aggressive 
B-cell NHL have poor outcomes and the efficacy of salvage options are diminished in the era of 
rituximab-containing regimens. As such, there remains a need to develop new therapies for 
patients with R/R B-cell NHL.
Historically, first-line treatment for patients with high-stage aggressive B-cell NHL, including 
DLBCL, primary mediastinal B-cell lymphoma (PMBCL), and follicular lymphoma Grade 3B, 
has been 6 or 8 cycles of rituximab with cyclophosphamide, doxorubicin, vincristine, and 
prednisone (R-CHOP), with reduced-intensity dosing regimens recommended for infirm or 
elderly patients > 80 years of age (NCCN 2019). Recently, data have been reported that support 
the use of more intensive therapy for PMBCL in the upfront setting (NCCN 2019), and ongoing 
studies are evaluating the effect of augmented RCHOP regimens on outcomes in high-risk 
subtypes of aggressive B-cell NHL.
Approximately one-third of DLBCL patients will be refractory to or relapse after R-CHOP 
therapy within 5 years of diagnosis (Cunningham 2013). Patients at high risk of relapse to 
R-CHOP include those with a high international prognostic index (IPI) score (Ziepert 2010, 
Cunningham 2013), those with activated B-cell or nongerminal center B-cell (GCB) origin (Fu 
2008, Culpin 2013), and double-hit DLBCL, now referred to as high-grade B-cell lymphoma 
with MYC and BCL2 and/or BCL6 rearrangements (Friedberg 2012, Morgan 2013). In these 
high-risk groups, 50% or less of patients are disease-free at 2 years (Ziepert 2010, Culpin 2013, 
Morgan 2013). Overall survival (OS) for all DLBCL patients approaches 75% at 5 years 
(Cunningham 2013); however, in high-risk patients, it may be as low as 25% to 30% (double-hit 
and non-GCB) to 50% (IPI 3 to 5) at 5 years (Ziepert 2010, Culpin 2013, Morgan 2013).
For patients who are refractory to or relapse following front-line therapy and are eligible for 
autologous hematopoietic stem cell transplant (auto-HSCT), various high-dose, platinum-based 
salvage chemotherapy regimens are recommended (NCCN 2019). It is estimated that 35% to 
50% of R/R patients are not suitable for high-dose chemotherapy, for reasons including (but not 
limited to) comorbidities, poor performance status, or age, and are thus not eligible for HSCT.
These patients may be treated with a platinum and/or gemcitabine-based regimen such as 
rituximab, or gemcitabine and oxaliplatin (R-GemOx), which may be combined with involved
field radiation therapy (El Gnaoui 2007), or preferentially be enrolled in clinical trials testing the 
activity of novel drugs or combinations of agents. The effectiveness of single-agent or 
combination therapies is limited to a minority of those treated. 
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There are 2 Food and Drug Administration (FDA)-approved treatment as a salvage regimen for 
patients with R/R aggressive large B-cell NHL after at least 2 prior therapies- axicabtagene 
ciloleucel and tisagenlecleucel (discussed further below). Because these therapies were recently 
approved (2017), most data on outcomes in this population are from patients treated with 
combinations of agents or monotherapy or experimental therapies in clinical trials based on 
institutional preferences. The most commonly used treatment is a combination of rituximab with 
bendamustine (~25%) (Crump 2017). The effectiveness of combination and single-agent 
therapies for multiply relapsed, aggressive B-cell NHL is limited to a minority of those treated; 
specifically, the ORR (12% to 46%) and complete response (CR) rates (6% to 38%) are low; 
median PFS (< 6 months) and median OS (< 12 months) results are equally poor (Pettengell 
2012, Rigacci 2012, Mounier 2013, Nagle 2013, Wang 2013, Czuczman 2014, Jacobsen 2015, 
Van Den Neste 2016). In a study of the most commonly used combination, rituximab and 
bendamustine, an ORR of 45% with a 15.5% CR was reported in patients with R/R DLBCL; 
median PFS was only 3.6 months (Vacirca 2013). Importantly, most patients in this study had 
only 1 prior therapy (median = 1, range = 1 to 9. Overall outcomes for patients who have 
relapsed after multi-agent salvage chemotherapy and auto-HSCT, or were refractory to salvage 
therapy and were not eligible for an auto-HSCT, are equally poor with median OS of 9.9 and 4.4 
months, respectively (Nagle 2013, Van Den Neste 2016). In a recent meta-analysis of DLBCL 
patients who were refractory to their last chemotherapy-containing regimen or who relapsed 
within 12 months after auto-HSCT (the SCHOLAR-1 study), outcomes were even worse, with 
ORR of 26%, CR rate of 7%, and median OS of 6.3 months (Crump 2017). Therefore, there is 
significant unmet need for patients who have R/R B-cell NHL.
1.2.
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 (Stamenkovic 1988; Brentjens 2011). 
CD19 is an attractive therapeutic target because it is expressed by most B-cell malignancies, 
including B-cell NHL (Li 1993, Li 1996, 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. 
1.3.
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 CARs in autologous T cells (CAR T) is achieved by ex vivo transduction 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 CAR T cells have demonstrated encouraging activity in adult and 
pediatric subjects with R/R B-cell acute lymphoblastic leukemia (ALL) and B-cell NHL (Porter 
2011, Davila 2014a, Maude 2014, Kochenderfer 2015, Lee 2015, Park 2016, Turtle 2016a, 
Turtle 2016b, Turtle 2016c, Neelapu 2017, Schuster 2017).
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Two CD19-directed CAR therapies have recently been approved by the FDA: 

Tisagenlecleucel, approved for the treatment of patients up to 25 years of age with
relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic 
therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, 
high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
(KYMRIAH™[tisagenlecleucel] prescribing information, 2018). 

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
not otherwise specified (NOS), primary mediastinal large B-cell lymphoma, high 
grade B-cell lymphoma, and DLBCL arising from follicular lymphoma 
(YESCARTA® [axicabtagene ciloleucel] prescribing information, 2019).
1.4.
JCAR017 Drug Product
The final JCAR017 investigational drug product includes 2 individually formulated CD4+CAR+
and CD8+CAR+ T-cell suspensions in media containing dimethyl sulfoxide (DMSO) that are 
thawed and infused separately. JCAR017 is administered by intravenous (IV) infusion.
The CD19-specific CAR is introduced into autologous CD4+ and CD8+ T cells ex vivo using a 
replication-incompetent, self-inactivating lentiviral vector. The CD19-specific CAR consists of 
an scFv binding domain derived from a murine CD19-specific monoclonal antibody (FMC63) 
and the 4-1BB and CD3ζ chain signaling domains. The truncated epidermal growth factor 
receptor (EGFRt) protein is expressed as a separate cell surface protein for purposes of cell 
tracking.
Please refer to the JCAR017 Investigator’s Brochure (IB) for detailed information concerning the 
available pharmacology, toxicology, clinical studies, and adverse event (AE) profile of 
JCAR017.
1.5.
Clinical Experience with JCAR017
Clinical study 017001 is an ongoing open-label, multicenter, pivotal Phase 1 study to determine 
the efficacy and safety of JCAR017 in adults with R/R aggressive B-cell NHL, including 
DLBCL-NOS (de novo and transformed from indolent lymphoma), high-grade B-cell lymphoma 
with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology, PMBCL, follicular 
lymphoma Grade 3B, and mantle cell lymphoma (MCL). Two disease-specific cohorts are being 
enrolled: the DLBCL cohort and the MCL cohort. Subjects in the DLBCL cohort must have been 
treated with an anthracycline and rituximab (or other CD20-targeted agent) and have R/R disease 
after at least 2 lines of therapy or after auto-HSCT.
As of 12 April 2019, 255 subjects with DLBCL have undergone lymphodepletion chemotherapy 
with low-dose fludarabine (30 mg/m2/day for 3 days) + cyclophosphamide (300 mg/m2/day for
3 days) (flu/cy) and were treated with JCAR017 at Dose Level 1 (50×106 JCAR017 cells), Dose 
Level 2 (100×106 JCAR017 cells), or Dose Level 3 (150x106 JCAR017 cells) and were evaluable 
for efficacy. The best response was a CR in 53% of subjects in the efficacy analysis set treated at 
any dose regimen with efficacy data. Overall, in a total of 268 treated subjects, 42% of subjects 
experienced cytokine release syndrome (CRS), and 6 subjects (2%) had Grade ≥3 CRS (none 
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was Grade 5). Neurotoxicity (NT) was observed in 30% of subjects, including 10% with
Grade ≥3 neurotoxicity (none was Grade 5) (Abramson, 2019). 
See the JCAR017 IB for further details.
2.
STUDY PURPOSE AND RATIONALE
The purpose of this Phase 2 study is to evaluate the safety and antitumor activity of JCAR017
administered in nontertiary care centers in adult subjects with R/R aggressive B-cell NHL who 
have failed 2 or more lines of therapy. 
Clinical trials of JCAR017 and other CAR T-cell products to date have been performed in 
tertiary care centers that have consolidated the site of care for CAR T-cell administration and 
follow-up. In the US, however, about 80% of patients receiving treatment for R/R DLBCL in 
third line are treated outside of these centers (data on file). The product profile of JCAR017 is 
conducive to outpatient administration and toxicity monitoring in hospital outpatient clinics and 
cancer clinic networks with toxicity management in an associated hospital setting; however, the 
safety profile of this product administered in nontertiary care centers has not been evaluated. 
Preliminary data from the ongoing Juno Study 017001 show that treatment of this patient 
population with JCAR017 demonstrates encouraging efficacy results and a manageable safety 
profile, including low rates of all grade and severe CRS and NT events. This supports outpatient 
administration and toxicity monitoring, with hospital admission upon symptoms of toxicity. 
Experience to date with JCAR017 in Study 017001 suggests that outpatient administration of 
JCAR017 can be provided safely with appropriate education and outpatient monitoring and can 
reduce the duration of inpatient hospital stays by 40% when compared to inpatient administration 
(Maloney 2017). Thus, a safety study to assess the use of JCAR017 in nontertiary outpatient 
settings is designed to confirm these initial findings.
2.1.
Rationale for JCAR017 Dose Level
In Study 017001, JCAR017 at flat doses of 50×106 CAR+ T cells and 100×106 CAR+ T cells 
resulted in durable responses and demonstrated an acceptable safety profile in the third-line or 
greater treatment of R/R aggressive DLBCL. 
Additionally, as of 09 Oct 2017, a trend toward improved ORR at 3 months was observed in 
patients treated at Dose Level 2 (100×106 CAR T+ cells) compared to Dose Level 1 
(50 ×106 CAR+ T cells): 62% (16/26; 95% CI: 41, 80) versus 48% (19/40; 95% CI: 31, 64). 
Based on these results, the dose of 100×106 CAR+ T cells has been chosen for development in 
the third-line setting. 
2.2.
Rationale for Study Design
The purpose of this Phase 2 study is to evaluate the safety and efficacy of JCAR017 administered 
in nontertiary care centers in adult subjects with R/R aggressive B-NHL (non-Hodgkin’s 
lymphoma) who have failed at least 2 prior lines of therapy. There is no approved standard of 
care for this population. A nonrandomized design was chosen because of the lack of effective 
therapies in this population (see Section 1.1), leading to concerns about comparing against an 
ineffective therapy given the promising preliminary efficacy results in third-line subjects (see
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Section 1.5). Similarly, enrollment to a randomized study versus another assigned treatment is 
likely to be difficult, given the lack of efficacy of currently used regimens and the number of 
clinical studies ongoing in this population. 
2.3.
Rationale for Lymphodepleting Chemotherapy
As noted in Section 1.5, preliminary data available from subjects with R/R NHL in 
Study 017001 suggest that the low-intensity lymphodepleting chemotherapy regimen used, 
cyclophosphamide (300 mg/m2/day × 3 days) combined with fludarabine (30 mg/m2/day × 
3 days) in combination with JCAR017, has adequate safety and good efficacy in subjects with 
R/R NHL. This lymphodepleting chemotherapy regimen was selected to limit toxicity and retain 
efficacy, as well as to optimize cellular expansion and efficacy after treatment with JCAR017. 
See the JCAR017 IB for more information. This same flu/cy dose is planned for the current 
017007 study. 
2.4.
Rationale for Endpoints
The safety to be assessed in this trial are standard assessments for oncology clinical trials and are 
appropriate for monitoring the safety of patients in the study. Several AEs of special interest 
(AESIs) are defined for this study, including CRS, NT, prolonged cytopenia, Grade ≥ 3 
infections, macrophage activation syndrome (MAS), tumor lysis syndrome (TLS), infusion 
reactions, hypogammaglobulinemia, autoimmune disorders, and second primary malignancies
because these events have been identified as potential risks associated with JCAR017 treatment 
as well as other CAR T-cell therapies.
The efficacy endpoints to be assessed in this study are standard endpoints for the assessment of 
aggressive B-cell NHL. Disease response will be determined according to the 
“Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and 
Non-Hodgkin Lymphoma: The Lugano Classification” (Cheson 2014). 
2.5.
Risk/Benefit Summary
As discussed in Section 1.1, options for treatment of R/R DLBCL are limited and few patients 
respond to chemotherapy in the third-line setting and beyond. Preliminary data on JCAR017
treatment from the ongoing Juno Study 017001 show that treatment of this patient population 
with JCAR017 demonstrates encouraging efficacy results and a manageable safety profile, 
including low rates of all grade and severe CRS and NT events, which support outpatient 
administration and toxicity monitoring. 
Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, 
tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia. Unique NT events 
have also been reported and may include neurologic symptoms such as altered mental status, 
aphasia, altered level of consciousness, and seizures or seizure-like activity. In Study 017001, 
these toxicities have generally been found to be manageable and reversible. Guidance regarding 
management of other safety events is provided in Section 7. A detailed management algorithm 
for the assessment and treatment of signs of CRS and NT is provided in 
Experience with JCAR017 to date in Study 017001 further suggests that outpatient 
administration of JCAR017 can be provided safely with appropriate education and outpatient 
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monitoring for toxicity with hospitalization and inpatient toxicity management when required; 
this strategy can reduce the duration of inpatient hospital stays by 40% when compared to 
inpatient administration (Maloney 2017). 
Thus, a safety study to assess the use of JCAR017 in nontertiary outpatient settings has been 
designed to confirm these initial findings.
Overall, considering the poor prognosis in R/R subjects receiving third-line treatment and the 
potential for good responses with a manageable safety profile with JCAR017, the benefit/risk is 
considered to be positive in this population treated in nontertiary outpatient settings. 
3.
STUDY OBJECTIVES AND ENDPOINTS
The objectives and corresponding endpoints for the study are presented in Table 1. Efficacy 
analyses will be based on response assessments according to the Investigators.
Table 1:
Study Objectives and Endpoints
Objective
Endpoints
Primary 
To evaluate the safety of JCAR017 administered 
in nontertiary care centers as reflected by Grade ≥ 
3 adverse events (AEs) of CRS, NT, prolonged 
cytopenias, and infections in adult subjects with 
relapsed or refractory (R/R) aggressive B-cell non-
Hodgkin lymphoma (NHL)

Incidence of CRS, NT, prolonged cytopenia and 
infection AEs Grade ≥3
Secondary 
To evaluate the overall safety and tolerability of 
JCAR017, including toxicity management and 
outcomes 

Type, frequency, and severity of all AEs and 
laboratory abnormalities

Incidence of Grade ≥3AEs

Median time to onset and median time to resolution of 
Grade ≥3 CRS and NT

Use of tocilizumab and glucocorticoids for 
management of CRS/NT
To evaluate the safety of JCAR017 treatment in 
subjects monitored as an outpatient 

Type, frequency, and severity of all AEs and 
laboratory abnormalities
To assess the antitumor activity of JCAR017

Objective response rate (ORR [CR + partial response]) 

CR rate

Duration of response (DOR) and duration of complete 
response (DoCR), each defined as the time from first 
response to progressive disease (PD) or death 

PFS, defined as the time from infusion of JCAR017 to 
PD or death, whichever is earlier

OS, defined as the time from infusion of JCAR017 to 
the date of death
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4.
STUDY DESIGN AND INVESTIGATIONAL PLAN
4.1.
Overall Study Design
This is an open-label, multicenter, Phase 2 study to determine the safety and efficacy of 
JCAR017 in subjects who have R/R aggressive B-cell NHL who will be treated in the outpatient 
setting. Subjects will be treated with JCAR017 after completing lymphodepleting chemotherapy. 
There will be no control group for this study.
A total of 114 subjects may be enrolled to ensure that approximately 80 subjects are treated with 
JCAR017, with a minimum of approximately 50 treated subjects monitored as an outpatient.
A schematic of treatment for each subject is provided in Figure 1. Subjects will undergo 
leukapheresis to collect peripheral blood mononuclear cells to enable JCAR017 product 
generation. Subjects who commence leukapheresis are considered enrolled on the day of 
leukapheresis. While JCAR017 is being manufactured and if required to control disease, subjects 
may receive salvage low-dose chemotherapy or 1 cycle of noncurative standard-of-care 
antitumor therapy as described in Section 8.2.2. 
Upon successful JCAR017 product generation, subjects will enter the treatment phase and will 
receive JCAR017 treatment. Treatment includes lymphodepleting chemotherapy with 
fludarabine/cyclophosphamide (flu/cy) followed by JCAR017 administration 2 to 7 days after 
completing lymphodepleting chemotherapy. 
After completion of JCAR017 treatment, subjects will enter post-treatment follow-up, and will 
be followed on this study for 2 years for safety, disease status, health-related quality of life 
(HRQoL), and survival, as described in more detail in Section 8. After completion of 2 years of 
assessments in this protocol, long-term follow-up (LTFU) for survival, long-term toxicity, and 
viral vector safety will continue under a separate protocol for up to 15 years after JCAR017
treatment.
Toxicity will be evaluated on an ongoing basis by the study team and reviewed at regularly 
scheduled Investigator Safety calls. Additionally, safety monitoring boundaries based on the 
incidence of Grade 3 or above JCAR017-related adverse events of special interest (AESI) will be 
established using a Bayesian framework (Thall 1994) as described in Section 10.3.5.4 and the 
statistical analysis plan. If the safety boundaries are crossed, enrollment will be paused and an ad 
hoc SRC will meet to review the data. The study will remain paused for enrollment pending the 
SRC’s recommendations.
Figure 1:
Study Schema for Individual Subjects
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CT = computed tomography; LTFU = long-term follow-up; PET = positron-emission spectroscopy.
4.2.
Study Duration and Duration of Subject Participation
The duration of study for each subject is up to 2 years and the estimated total time for all subjects 
to complete the study is approximately
years. All subjects who receive JCAR017 will be 
eligible to enroll in the LTFU protocol after completion of this study (see Section 8.2.10.).
4.3.
Study Completion
A subject is considered to have completed the study if he/she has completed the last scheduled 
visit shown in the Schedule of Evaluations (see Appendix A).
The end of the study is defined as the date of the last scheduled assessment shown in the 
Schedule of Evaluations for the last subject in the trial.
4.4.
Study Oversight
A Safety Review Committee (SRC), comprised of Principal Investigators and the Sponsor’s 
medical monitor, safety physician, and statistician, will regularly assess the safety of JCAR017
administration throughout the trial. The SRC may make recommendations based on safety.
4.5.
Suspension or Early Termination of the Study
The study can be suspended or terminated at any time by the Sponsor, the FDA, or at the 
recommendation of the Investigational Review Board (IRB). Circumstances that may warrant 
suspension or termination include, but are not limited to:

Determination of unexpected, significant, or unacceptable risk to subjects

Demonstration of efficacy that would warrant stopping

Determination that the primary endpoint has been met 

Insufficient compliance to protocol requirements

Data that are not sufficiently complete and/or evaluable
If the study is suspended or terminated for safety reasons, the Sponsor will promptly inform the 
Investigator, and will also inform the regulatory authorities of the suspension or termination of 
the study and the reasons for the action. The Investigator may be informed of additional 
procedures to be followed in order to ensure adequate protection of subjects. The Investigator 
will be responsible for promptly informing the IRB, other applicable regulatory committees, and 
study subjects of the suspension or early termination of the trial, including the reasons for 
suspension or termination and any other regulatory committee, as applicable.
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed to the satisfaction of the Sponsor, IRB, and/or FDA.
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5.
STUDY POPULATION
5.1.
Inclusion Criteria
Subjects must meet all of the following criteria to be enrolled in this study: 
1. Age ≥ 18 years at the time of consent 
2. Signed written informed consent prior to any study procedures 
3. Relapsed or refractory B-cell NHL of the following histologies: 
DLBCL NOS; includes biopsy-confirmed transformed DLBCL from indolent histologies, 
high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with 
DLBCL histology, primary mediastinal B-cell lymphoma (PMBCL) and follicular 
lymphoma Grade 3B. Subjects must have been treated with an anthracycline and 
rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at 
least 2 systemic lines of therapy for DLBCL or after auto-HSCT. 
4. Positron-emission tomography (PET)-positive disease according to the 
“Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin 
and Non-Hodgkin Lymphoma: The Lugano Classification” (Cheson 2014).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 
6. Adequate organ function (must meet all), defined as: 
a.
Assessed by the Investigator to have adequate bone marrow function to receive 
lymphodepleting chemotherapy
b. Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN), OR if greater 
than 1.5× ULN then calculated creatinine clearance (Cockcroft and Gault) 
> 30 mL/min
c.
Alanine aminotransferase (ALT) ≤ 5 × 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) 
d. Adequate pulmonary function, defined as ≤ Common Terminology Criteria for 
Adverse Events (CTCAE) Grade 1 dyspnea and oxygen saturation (SaO2) ≥ 92% on 
room air 
e.
Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥40% 
as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition 
(MUGA) scan performed within 1 month of determination of eligibility 
7. Adequate vascular access for leukapheresis procedure (either peripheral line or surgically 
placed line) 
8. Subjects who have received previous CD19-targeted therapy must have CD19-positive 
lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy 
9. Females of childbearing potential* must: 
a.
Have 2 negative pregnancy tests as verified by the Investigator (one negative serum 
beta-human chorionic gonadotropin [ß-hCG] pregnancy test result at screening, and 
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within 48 hours prior to the first dose of lymphodepleting chemotherapy). This 
applies even if the subject practices true abstinence** from heterosexual contact. 
b. Either commit to true abstinence** from heterosexual contact or agree to use, and be 
able to comply with, effective contraception without interruption. Contraception 
methods must include 1 highly effective method of contraception from screening until 
at least 12 months after receiving lymphodepleting chemotherapy. 
c.
Agree to abstain from breastfeeding during study participation and for at least 12 
months following lymphodepleting chemotherapy. 
d. There are 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.
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 highly effective and additional effective methods of contraception:

Intrauterine device (IUD)

Hormonal (birth control pill, injections, implants)

Tubal ligation 

Partner's vasectomy
10. Males who have partners of childbearing potential must:
a.
Practice true abstinence** or agree to use a condom during sexual contact with a 
pregnant female or a female of childbearing potential for 12 months after 
lymphodepleting chemotherapy even if he has undergone a successful vasectomy.
b. There are 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.
c.
Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for 
usage in other individuals for at least 1 year following lymphodepleting 
chemotherapy. There are insufficient exposure data to provide any recommendation 
concerning the duration of refraining from tissue donation following treatment with 
JCAR017. Therefore, subjects treated with JCAR017 should not donate blood, 
organs, tissues, and cells for transplantation.
* A female subjects of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some 
point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally 
postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 
12 consecutive months (ie, has had menses at any time in the preceding 12 consecutive months).
**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.
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5.2.
Exclusion Criteria:
Subjects who meet any of the following criteria will be excluded from participation in this study:
1. Subjects with central nervous system (CNS)-only involvement by malignancy (note: 
subjects with secondary CNS involvement are allowed on study) 
2. History of prior allogeneic hematopoietic stem cell transplant (allo-HSCT)
3. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with 
fludarabine or cladribine within 3 months of leukapheresis 
4. History of another primary malignancy that has not been in remission for at least 2 years. 
The following are examples of exceptions from the 2-year limit: nonmelanoma skin 
cancer, definitively-treated stage 1 solid tumor with a low risk of recurrence, curatively-
treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous 
intraepithelial lesion on a Papanicolau smear. 
5. Subjects with a history of or active human immunodeficiency virus (HIV) are excluded.
6.
Subjects with active hepatitis B, or active hepatitis C are also excluded. Subjects with a 
negative 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.  
7. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite 
appropriate anti-infection treatment at the time of leukapheresis or JCAR017
administration 
8. Presence of acute or chronic graft-versus-host disease (GVHD) 
9. History of any 1 of the following cardiovascular conditions within the past 6 months: 
Class III or IV heart failure as defined by the New York Heart Association, cardiac 
angioplasty or stenting, myocardial infarction, unstable angina, or other clinically 
significant cardiac disease 
10. History or presence of clinically relevant CNS pathology such as epilepsy/seizure, 
paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson’s 
disease, cerebellar disease, organic brain syndrome, or psychosis 
11. Pregnant or nursing women. NOTE: Women of reproductive potential must have a 
negative serum pregnancy test performed within 48 hours of starting lymphodepleting 
chemotherapy 
12. Use of any of the following: 
a.
Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or 
equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017
administration. Physiologic replacement, topical, and inhaled steroids are permitted. 
b. Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤300 mg/m2) 
given after leukapheresis to maintain disease control must be stopped ≥7 days prior 
to lymphodepleting chemotherapy. 
c.
Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) 
within 1 week of leukapheresis. Oral chemotherapeutic agents, including 
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lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to 
leukapheresis. 
d. Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, 
bendamustine) within 2 weeks of leukapheresis 
e.
Experimental agents within 4 weeks of leukapheresis unless no response or disease 
progression is documented on the experimental therapy and at least 3 half-lives have 
elapsed prior to leukapheresis 
f.
Immunosuppressive therapies within 4 weeks of leukapheresis and JCAR017
administration (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, 
mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as 
antitumor necrosis factor (TNF), anti-interleukin 6 (IL6), or anti-interleukin 6 
receptor (IL6R) 
g. Donor lymphocyte infusions within 6 weeks of JCAR017 administration 
h. Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease 
(PD) in irradiated lesions or have additional nonirradiated, PET-positive lesions to be 
eligible. Radiation to a single lesion, if additional nonirradiated PET-positive lesions
are present, is allowed up to 2 weeks prior to leukapheresis. 
13. Uncontrolled medical, psychological, familial, sociological, or geographical conditions 
that do not permit compliance with the protocol, as judged by the Investigator; or 
unwillingness or inability to follow the procedures required in the protocol 
14. Prior CAR T-cell or other genetically modified T-cell therapy
15. Progressive vascular tumor invasion, thrombosis, or embolism
16. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
5.3.
Removal of Subjects from Treatment or Study 
At the time of consent, subjects will be advised that they are free to withdraw consent from the 
study at any time for any reason; however, all subjects who have received treatment with 
JCAR017 will be encouraged to continue all study evaluations through the End-of-Study (EOS) 
visit as well as participate in the LTFU study. The Sponsor must be notified if a subject has 
withdrawn consent from the study or has requested to discontinue treatment, and the reason(s) 
must be documented. 
5.3.1.
Screen Failures
Screening failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently enrolled in the study (Enrollment is described in Section 8.2.1). A minimal set 
of screen failure information is required to ensure transparent reporting of screen failure subjects 
to meet the Consolidated Standards of Reporting Trials publishing requirements and to respond 
to queries from regulatory authorities. Minimal information includes demography, eligibility 
criteria assessment, and any protocol procedure-related serious adverse event (SAE).
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened with a new subject number.
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5.3.2.
Subject Discontinuation Prior to Receiving Study Treatment
Subjects who undergo leukapheresis but do not receive lymphodepleting chemotherapy or 
JCAR017 will be followed for survival (see Section 8.2.9). 
A subject’s treatment may not occur for any of the following reasons:

Subject did not receive study treatment due to disease-related complications

Subject did not receive study treatment due to interim treatment-related toxicities

Subject did not receive study treatment because the subject no longer meets eligibility 
criteria for other reasons (not related to disease or interim treatment)

JCAR017 could not be manufactured 

Death

Other
5.3.3.
Subject Discontinuation from Further Study Treatment
In the rare event that a subject receives only a partial dose of JCAR017 (eg, CD8+CAR+ cells 
only), the subject should be reported as discontinuing treatment. Reasons for discontinuing 
treatment will include the following:

Adverse event (AE)

Investigator decision

Subject decision

Other
Subjects who are discontinued from treatment will not be withdrawn from the study. The subject 
will remain on study and continue to have all scheduled evaluations through the EOS visit per 
the Schedule of Evaluations (see Appendix A).
5.3.4.
Subject Withdrawal from Study
A subject may be withdrawn from the study for any of the following reasons:

Subject withdrawal of consent

Study termination by Sponsor

Lost to follow up

Death

Other
See the Schedule of Evaluations in Appendix A for data to be collected at the EOS visit.
5.3.5.
Replacement of Study Subjects 
Subjects who sign the informed consent form but do not receive at least 1 dose of JCAR017 will 
be replaced. Subjects who receive nonconforming product (see Section 6.3.2) will be followed 
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per protocol, but will be excluded from certain analysis sets (as noted in Section 10.2) and will 
be replaced. All enrolled subjects will be assigned a unique subject number.
6.
STUDY TREATMENTS
6.1.
Leukapheresis
Following enrollment on 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 investigational product. Should a technical issue arise during the procedure or in 
the processing of the product such that it cannot be used for JCAR017 administration, the subject 
may have subsequent collection procedure(s) performed. Subjects must continue to meet 
eligibility requirements for repeat leukapheresis; see Section 8.2.3.1 for information about 
assessments that do not need to be repeated for additional apheresis.
Please refer to the PBMC collection manual for further details.
6.2.
Anticancer Treatments between Leukapheresis and 
Lymphodepleting Chemotherapy
If necessary, anticancer treatment is allowed for disease control while JCAR017 is being 
produced (ie, after leukapheresis and prior to lymphodepleting chemotherapy). Low dose 
chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2) is allowed if 
completed at least 7 days prior to the start of lymphodepleting chemotherapy. If other agents are 
used, the washout periods noted in the exclusion criteria (see Section 5.2) must be met. The use 
of therapeutic agents with little/no evidence in the scientific literature for DLBCL should be 
discussed with the Sponsor. Local radiation is allowed to a single lesion or subset of lesions if 
other un-irradiated PET-positive lymphoma lesions are present. If anticancer treatment is 
necessary during this time, the pretreatment PET and computed tomography (CT) assessments 
and other pretreatment study procedures (see Section 8.2.4) must be performed after the 
anticancer treatment has been completed. The subject must continue to have PET-positive 
disease and meet eligibility criteria pertaining to adequate organ function, active infections, 
pregnancy, and washout of prior therapy before initiation of lymphodepleting chemotherapy.
6.3.
JCAR017 Investigational Drug Product
The JCAR017 investigational drug product is comprised of autologous CD8+ and CD4+ T cells 
that express a CD19-specific CAR that are provided as frozen cell suspensions for intravenous 
(IV) administration. The JCAR017 investigational drug product is provided as 2 individually 
formulated CD4+CAR+ and CD8+CAR+ T-cell suspensions in media containing DMSO for 
direct IV administration in equal CAR T-cell quantities into the subject.
The CD19-specific CAR is introduced into autologous CD8+ and CD4+ T cells ex vivo using a 
replication-incompetent, self-inactivating lentiviral vector. The CD19-specific CAR consists of 
an scFv binding domain derived from a murine CD19-specific monoclonal antibody (FMC63) 
and the 4-1BB and CD3ζ chain signaling domains. 
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A Celgene Company
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See the JCAR017 Product Administration Manual for details of packaging and labeling, product 
tracking and accountability, and product disposal and destruction.
6.3.1.
Protocol Product Deviation Plan 
The JCAR017 Protocol Product Deviation Plan (PPDP) addresses the use of 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 
JCAR017). 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.
6.3.2.
Exception Use of Non-conforming Product
Once a decision is made for the exception use of non-conforming JCAR017, country specific
requirements will be followed for the release of a non-conforming JCAR017 product to treat a 
subject enrolled in a JCAR017 clinical trial. For example, approval from local health authorities 
and/or IRBs/ECs will be obtained where required. Any subject will need to provide consent by 
signing the site’s IRB approved non-conforming product ICF prior to receiving the non-
conforming JCAR017 product. While subjects treated with non-conforming product will be 
followed as per the Table of Events (Appendix A) listed in the protocol, their data will be 
excluded from the primary safety/efficacy evaluable analysis. Their data will be analyzed 
separately (Section 10.2.4). 
Subjects treated with non-conforming product will be replaced for the purposes of study 
enrollment of per protocol evaluable subjects.
6.3.3.
Dose and Schedule
The dose of JCAR017 will be 100×106 CAR+ T cells. JCAR017 will be administered 2 to 7 days 
after completion of lymphodepleting chemotherapy, described in Section 8.2.5.2. Subjects must 
meet the criteria for treatment specified in Section 8.2.5.3.
6.3.4.
Lymphodepleting Chemotherapy
Subject eligibility criteria must be confirmed immediately prior to starting the first cycle of 
lymphodepleting chemotherapy (see Section 8.2.5.1). The last dose of lymphodepleting 
chemotherapy must be administered 2 to 7 days before JCAR017 administration.
Subjects will be treated with fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide 
(300 mg/m2/day for 3 days) prior to treatment with JCAR017. The fludarabine dose should be 
reduced based on renal function. See Section 8.2.5 for the recommended schedule of 
administration and for the assessments that will be performed during lymphodepleting 
chemotherapy. Refer to the most recent package inserts for further details on administration of 
these agents. 
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Serum creatinine will be measured on the first day of lymphodepleting chemotherapy; 
chemotherapy should be withheld if serum creatinine is > 1.5 times the age-adjusted ULN OR 
calculated creatinine clearance (Cockcroft and Gault; Appendix C) or radioisotope glomerular 
filtration rate (GFR) is ≤30 mL/min. Delay of lymphodepleting chemotherapy by more than 
14 days requires discussion with the Sponsor and may require rescreening (see Section 8.2.5.2).
Antiemetic therapy may be given prior to lymphodepleting chemotherapy per institutional 
practice. Mesna may be used for subjects with a history of hemorrhagic cystitis per institutional 
practice.
6.3.5.
JCAR017 Premedication
Subjects should be pre-medicated with 650 mg acetaminophen PO and 25–50 mg 
diphenhydramine hydrochloride (PO or IV) 30–60 minutes prior to JCAR017 administration. 
These medications may be repeated every 6 hours as needed based on the Investigator’s 
assessment of symptoms. Pre-medication with steroids is not allowed. See Section 6.6 for further 
guidance on steroid use and Section 7.5 for further information on infusion reactions.
6.3.6.
JCAR017 Preparation and Cell Thawing
See the JCAR017 Product Administration Manual for details.
6.3.7.
JCAR017 Administration
JCAR017 may be delivered in an outpatient setting at the Investigator’s discretion. This setting is 
not recommended for the following subjects:

Subjects who do not have adequate caregiver support

Subjects who are staying greater than 60 minutes from the clinical trial site at the time 
of treatment.
Each JCAR017 dose consists of CD4+ CAR+ T cells and CD8+ CAR+ T cells, administered 
separately via IV. The subject must be continuously monitored during each 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, and within approximately 15 
minutes after the last IV administration, and then 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. 
Each T-cell suspension (CD8+ cells or CD4+ cells) must be thawed and the labeled dose volume 
administered into the subject within the specified expiration time after removal from shipping 
container or liquid nitrogen (LN2) freezer (if storing product on-site). If JCAR017 has been 
outside of the shipping container or LN2 freezer for longer than 2 hours, the product should be 
withheld, and the Sponsor study team immediately notified.
See the JCAR017 Product Administration Manual for complete information.
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A Celgene Company
Confidential and Proprietary
40
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6.3.8.
Acute Infusion Reactions
Acute infusion reactions may occur with administration of JCAR017. Guidelines for the 
treatment of acute infusion reactions are provided in Section 7.7.
6.4.
Recommended Supportive Care, Additional Treatment, and 
Monitoring
Prophylactic treatment/measures are strongly recommended for subjects at risk for TLS, per 
institutional or clinical standards. Supportive care for the management of CRS is detailed in 
 In some cases, tocilizumab, an anti-IL-6R-antibody, may be required to treat 
toxicities such as severe cytokine release syndrome (sCRS).  Please refer to currently approved 
RoActemra® Summary of Product Characteristics (RoActemra SmPC, 2015). 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 for the approved CAR Ts. The Sponsor requires that all JCAR017 sites must have at 
least 2 doses of tocilizumab available prior to infusion for each subject in the initial 30-day post-
JCAR017 infusion period. If site utilizes more than one pharmacy facility, 2 doses of tocilizumab
per subject are required in each pharmacy facility. 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 
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.
Prophylactic treatment measures for neurological toxicities are detailed in 
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 prophylaxis [PJP], broad spectrum antibiotics, antifungals, or antiviral 
agents for febrile neutropenia) is permitted per institutional standards.
Hospitalization may be required after treatment with JCAR017 to manage any treatment-
associated toxicities. Subjects who do not have adequate support outside of the hospital or do not 
meet outpatient monitoring guidelines as per Section 8.2.5.5 should be considered for 
hospitalization during the initial monitoring period following JCAR017 treatment.
6.5.
Concomitant Medications
Reporting periods for concomitant medications are summarized in Table 2. Management of 
potential risks is described in Section 7.
Table 2:
Reporting Periods for Concomitant Medications
Reporting Period
What to Record/Report
Initial Informed Consent to first day of 
administration of lymphodepleting chemotherapy
Medications taken at the time of AEs/SAEs related to 
protocol-mandated procedures must be recorded/reported
From first day of administration of 
lymphodepleting chemotherapy to 90 days 
All medications must be recorded/reported
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A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
Reporting Period
What to Record/Report
following last administration of JCAR017, or to 
EOS visit, whichever is earlier
Table 2:
Reporting Periods for Concomitant Medications (Continued)
Reporting Period
What to Record/Report
From 91 days following last administration of 
JCAR017 until EOS visit
Record/report the following:
•
Medications used at the time of AEs/SAEs related to 
JCAR017 and/or protocol-related procedures
•
Corticosteroids
•
Medications for the treatment of GVHD
•
Anticancer therapies
AE = adverse event; EOS = end of study; GVHD = graft versus host disease; SAE = serious adverse event.
The use of prophylactic or empiric anti-infective agents (eg, trimethoprim/sulfamethoxazole for 
pneumocystis pneumonia [PJP] prophylaxis, broad spectrum antibiotics, antifungals, or antiviral 
agents for febrile neutropenia) is permitted per institutional standards. Vaccination with an 
inactivated vaccine is permitted at any time in consultation with the medical monitor.
Subjects should be discouraged from using illicit drugs, herbal remedies, self-prescribed drugs, 
tobacco products, or excessive alcohol at any time during the clinical study.
For subjects receiving lymphodepleting chemotherapy but not JCAR017, concomitant 
medications associated with AEs/SAEs will be recorded for 30 days following the last dose of 
lymphodepleting chemotherapy.
Medications and transfusions given, and procedures performed for a pre-existing condition that 
is ongoing at LDC, should be reported as described in the CRF compliance guidelines (CCGs).
6.5.1.
Medications Administered During Hospitalizations
Due to the large amount of data generated during hospitalizations, a targeted concomitant 
medication collection approach will be used in the electronic case report form (eCRF). Therefore 
medications that should NOT be entered on the eCRF during inpatient and Intensive Care Unit 
(ICU) stays are defined in the CRF completion guidelines.
6.6.
Prohibited Medications
Chemotherapy given after leukapheresis to maintain disease control must be stopped ≥ 7 days 
prior to lymphodepleting chemotherapy.
The following medications are prohibited until the subject fails to respond, receives subsequent 
therapy for lymphoma, or 1 year has elapsed following JCAR017 treatment, whichever comes 
first:

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.
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Protocol 017007 
A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020

Steroids: therapeutic doses (> 20 mg/day of prednisone or equivalent) unless used for 
treatment of CRS or NT. Therapeutic doses may be used in life-threatening situations 
and for other medical conditions when indicated, or after loss of detectable JCAR017
cells. Pretreatment containing steroids may be given for necessary medications (eg, 
intravenous immunoglobulin [IVIG]) after discussion with the Sponsor. 
Premedication with steroids for JCAR017 administration 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 they 
are used as an anticancer agent after a subject fails to respond to JCAR017 or exhibits 
progression of their lymphoma:

Donor lymphocyte infusion (DLI)

Non-protocol specified anticancer agents. Lymphocytic cytotoxic chemotherapy may 
be administered as an extraordinary measure to treat AEs of uncontrolled JCAR017
proliferation, CRS, or neurotoxicity unresponsive to other therapeutic interventions

Cetuximab, or other anti-epidermal growth factor receptor (EGFR) treatments, unless 
intended for treatment of uncontrolled JCAR017 proliferation or sCRS

Experimental agents

Radiation, unless needed for local control of a single tumor lesion in the presence of 
other nonirradiated PET-positive lesions
7.
POTENTIAL RISKS AND MANAGEMENT OF TOXICITIES 
A summary of management of potential treatment toxicity is provided below.  See the JCAR017
IB for a complete discussion of potential risks associated with JCAR017. Cytokine release 
syndrome (CRS) and neurotoxicity (NT) are associated with CAR T-cell therapies. Celgene has 
developed specific 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 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 eCRF to inform future modifications of the 
management guidelines.
7.1.
Cytokine Release Syndrome 
Administration of CAR T cells, such as JCAR017, is associated with CRS. 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 
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Protocol 017007 
A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
are highly variable (Lee 2014), and management can be complicated by concurrent conditions. 
With JCAR017, CRS usually occurs within 2 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. 

Neurotoxicity has been observed concurrently with CRS.

CRS has been reported in a few cases to be associated with findings of 
MAS/hemophagocytic lymphohistiocytosis (HLH), and the physiology of the 
syndromes may overlap.
Please refer to 
for a detailed description of CRS, grading, and treatment 
recommendations. If available and adopted as per site standard practice, CRS and neurological 
toxicity (NT) grading according to the ASTCT Consensus Grading System (Lee, 2019) should 
also be recorded in the eCRF to inform future modifications of the management guidelines.
7.2.
Fever
The possibility of CRS should be considered for all subjects with fever (≥38.0ºC or ≥100.4ºF) 
following JCAR017 treatment. Subjects should be monitored closely for hemodynamic 
instability and changing neurologic status. Febrile subjects, neutropenic or otherwise, should be 
evaluated promptly and managed per institutional or standard clinical practice. 
The possibility of CRS should be considered for all subjects with fever following JCAR017
infusion. Subjects should be monitored closely for hemodynamic instability and changing 
neurologic status.
7.3.
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 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.
Please refer to 
for detailed descriptions of neurologic toxicities, grading, and 
treatment recommendations. Note: Tocilizumab is not indicated for the treatment of neurologic 
toxicities. 
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Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
44
Protocol 017007 Amendment 2.0: 17 Mar 2020
7.4.
Macrophage Activation Syndrome
Macrophage activation syndrome is a serious disorder potentially associated with uncontrolled 
activation and proliferation of CAR T cells and subsequent activation of macrophages (See the 
JCAR017 IB for further background about MAS). Macrophage activation syndrome is typically 
characterized by high-grade, non-remitting fever, cytopenias, 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.
Subjects treated with JCAR017 should be monitored for MAS, and cytokine-directed therapy 
should be considered as clinically indicated.
7.5.
Infusion Reactions
Administration of JCAR017 may cause infusion reactions, including 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. In case a subject cannot 
tolerate diphenhydramine, an equivalent antihistamine may be substituted. Mild infusion 
reactions should be managed expectantly with antipyretics, antihistamines, and antiemetics. 
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 administration both 
CD8+CAR+ and CD4+CAR+ components at the same dose and rate
Grade 2: stop administration of JCAR017; administer symptomatic treatment; resume 
JCAR017 administration of both CD8+CAR+ and CD4+CAR+ components at a reduced rate 
only after symptoms resolve
Grade 3: stop administration of JCAR017, administer symptomatic treatment, and resume 
JCAR017 administration of both CD8+CAR+ and CD4+CAR+ components at a reduced rate 
of administration only after symptoms resolve. If a Grade 3 reaction recurs, discontinue 
JCAR017; no further CD8+CAR+ or CD4+CAR+ components of JCAR017 should be 
administered
Grade 4: discontinue administration of JCAR017 and administer symptomatic treatment as 
necessary; no further CD8+CAR+ or CD4+CAR+ components of JCAR017 should be 
administered
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Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
7.6.
Tumor Lysis Syndrome 
Both the lymphodepleting chemotherapy employed in this protocol and JCAR017 therapy have 
caused TLS in adult B-NHL subjects with high disease burden. Subjects should be closely 
monitored for laboratory evidence of TLS (hyperuricemia, hyperkalemia, hyperphosphatemia, 
and hypocalcemia), 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, rasburicase or equivalent, and hydration, per standard clinical practice. 
7.7.
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 IgG < 500 mg/dL) 
should be considered for IV immunoglobulin replacement therapy per institutional guidelines. 
7.8.
Cytopenias
Severe (Grade ≥ 3) cytopenias including anemia, leukopenia, neutropenia, and 
thrombocytopenia, can occur with JCAR017 and lymphodepleting chemotherapy and delayed 
recovery has been observed. Complete blood counts (CBCs) should be monitored after JCAR017
infusions until count recovery. Follow institutional guidelines in the event of Grade ≥ 3 
cytopenias. 
7.9.
Infections
Life-threatening and fatal infections have been observed. Severe infections may include 
bacterial, fungal (including pneumocystis jirovecii), and viral infections (eg, CMV, 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.
7.10.
Graft-versus-host Disease
The likelihood of GVHD occurring with CAR T-cell therapy is low, and while it remains a 
theoretical risk, it does not apply to patients enrolled in this protocol (exclusion criteria #2, 8). 
See the JCAR017 IB for further details. 
7.11.
Uncontrolled T Cell Proliferation
JCAR017 could theoretically proliferate out of control. If uncontrolled JCAR017 T-cell 
proliferation occurs, subjects may be treated with high-dose steroids (eg, methylprednisolone 1 
to 3 g/kg/day, tapered over 1 week) or lymphodepleting doses of cyclophosphamide (1 to 3 g/m2
IV). If an Investigator suspects uncontrolled proliferation of JCAR017-transfected cells, the 
Sponsor should be contacted immediately. 
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EDMS Doc. Number: 24546003 - 22856872
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Protocol 017007 
A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
7.12.
Replication-competent Lentivirus, Clonality, and Insertional 
Oncogenesis 
Lentiviral vectors used in gene transfer are engineered to be replication-defective; however, 
generation of replication-competent lentiviruses (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 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 who received retroviral-
modified CD34+ hematopoietic stem cells (Hacein-Bey-Abina 2003), including 1 subject who 
died (Couzin 2005). Of note, no instances of RCL generation during production or lentivirus-
mediated malignant transformation in animals or humans 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 (Wang 2009, Scholler 2012, McGarrity 2013). 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.
Per the FDA Recombinant DNA Advisory Committee guidelines (FDA 2000), all subjects will 
be followed in this study for RCL and vector sequences for up to 15 years following JCAR017
treatment as part of a LTFU protocol. All subjects will be monitored for evidence of unexpected 
JCAR017 expansion and the emergence of a new second primary malignancy (SPM), 
particularly one of T-cell origin. Investigators must contact the Sponsor immediately if an 
unexpected pattern of JCAR017 expansion and/or a new SPM arises. 
Second primary malignancies will be monitored as events of interest and must be reported as 
serious adverse events. This includes any new malignancies, regardless of causal relationship to 
JCAR017, occurring throughout the subject’s entire participation in the study. If a subject 
develops a new malignancy, the Sponsor will request that a tumor sample, and blood samples are 
collected (see 017001 laboratory manual). See Section 8.3.12.
7.13.
Risks Associated with Lymphodepleting Chemotherapy
Subjects will receive fludarabine and cyclophosphamide prior to treatment with JCAR017 to 
facilitate lymphodepletion and CAR T-cell engraftment. Refer to the local package inserts for 
specific details surrounding the risks of fludarabine and cyclophosphamide.
8.
STUDY ASSESSMENTS AND PROCEDURES
A Schedule of Evaluations is provided in Appendix A. Specific visits are described in 
Section 8.2 and descriptions of study assessments are presented in Section 8.2.11.
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Protocol 017007 
A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
8.1.
Schedule of Evaluations
There are 3 parts to this study: pretreatment, treatment, and post-treatment. 
Pretreatment includes screening, leukapheresis, and pretreatment evaluation, and begins with 
assessing subject eligibility for study enrollment. If eligible, the subject will undergo 
leukapheresis as soon as possible, followed by pretreatment evaluation prior to lymphodepleting 
chemotherapy and JCAR017 administration. If needed, subjects may receive treatment between 
leukapheresis and lymphodepletion as described in Section 8.2.2.
All subjects will receive lymphodepleting chemotherapy prior to JCAR017. All subjects will be 
assessed for response at approximately Day 29.
Post-treatment includes safety and disease follow-up visits at approximately 2, 3, 6, 9, 12, 18, 
and 24 months after receiving JCAR017. The Month-24 visit will be the EOS visit.
8.2.
Study Visits
8.2.1.
Screening (Approximately 1 to 2 Weeks Prior to Leukapheresis) 
The screening process begins when the subject signs the IRB-approved informed consent 
document and continues until the subject is determined to be eligible and the subject is enrolled, 
or until screen failure is determined. If a subject has had a screening procedure as standard of 
care within 30 days of consent, it may be used to evaluate study eligibility. 
The following assessments will be performed during screening:

Obtain informed consent (obtained any time before study-related procedures are 
performed).

Assess eligibility per inclusion/exclusion criteria. All inclusion/exclusion criteria 
must be met in order for subjects to continue in the study. 

Obtain medical history, including: disease diagnosis and history, HSCT history, 
chemotherapy, radiation and surgical history. If applicable, report/record history of 
toxicities related to prior treatments and allergies.

ECOG performance status assessment (see

Physical examination (see Section 8.3.2)

12-lead electrocardiogram (ECG)

ECHO or MUGA scan

Local laboratory assessments (see Section 8.3.7):

Chemistries

CBC with differential

Viral serology

Serum beta subunit of human chorionic gonadotropin (ß-hCG) pregnancy test on 
women of child-bearing potential
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A Celgene Company
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
PET scan to confirm the presence of PET-positive lymphoma. PET scan may be 
performed longer than 30 days prior to screening if no intervening anticancer 
treatments have been performed.

Subjects with transformed DLBCL from indolent histologies (tDLBCL) must submit 
a pathology report documenting that that their current relapsed disease is biopsy-
confirmed tDLBCL 

If available, collection of tissue from latest archived tumor biopsy (block or slides) 
for tumor evaluation.

Record all AEs/SAEs related to protocol-mandated procedures and concomitant 
medications taken at that time (See Section 9.4.1 and Section 6.5, respectively)
8.2.2.
Optional Bridging Therapy for Disease Control Prior to Lymphodepleting 
Chemotherapy
Subjects may undergo an optional cycle of salvage low-dose chemotherapy (eg, vincristine, 
rituximab, cyclophosphamide ≤ 300 mg/m2) or noncurative standard-of-care chemotherapy for
disease control prior to leukapheresis and/or while JCAR017 is being manufactured (ie, between 
leukapheresis and lymphodepleting chemotherapy). Examples of acceptable regimens include:

Bendamustine plus rituximab (BR)

Rituximab, cyclophosphamide, etoposide, procarbazine, and prednisone (R-CEPP)

Rituximab, cyclophosphamide, epirubicin, and prednisone (R-CEOP)

Rituximab, gemcitabine, cisplatin, and dexamethasone (R-GDP)

Rituximab and lenalidomide
Other regimens may be acceptable after discussion with the Sponsor. 
Any selected regimen should be administered per institutional guidelines. Chemotherapy given 
after leukapheresis to maintain disease control must be stopped ≥ 7 days prior to 
lymphodepleting chemotherapy, and the washout periods noted in the exclusion criteria (see 
Section 8.2.3) must be met. The use of therapeutic agents with little/no evidence in the scientific 
literature for DLBCL should be discussed with the Sponsor. If clinically indicated, local 
radiation is allowed to a single lesion or subset of lesions if other un-irradiated PET-positive 
lymphoma lesions are present.
If bridging anticancer treatment is given, subjects must continue to meet eligibility criteria 
pertaining to adequate organ function, active infections, pregnancy, washout of prior therapy 
prior to lymphodepletion, and PET-avid disease. If the subject has not had any cardiotoxic 
medications or radiotherapy in which fields include the heart, screening assessments of cardiac 
function (MUGA/ECHO) do not need to be repeated. The pretreatment evaluations in 
Section 8.2.4 noted as required after any intervening anticancer therapy must be repeated. 
If lymphodepleting chemotherapy is delayed more than 14 days due to recovery from anticancer 
treatment, the subject must repeat eligibility assessments (some procedures may not be required 
after discussion with the Sponsor).
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A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
8.2.3.
Leukapheresis (Approximately 4 Weeks Prior to JCAR017 Administration)
Following enrollment on the study, a leukapheresis collection will be performed on each subject 
to obtain a sufficient quantity of PBMCs for the production of the JCAR017 investigational 
product (See Table 3 for washout periods prior to leukapheresis). Should a technical issue arise 
during the procedure or in the immediate processing of the product such that it cannot be used 
for JCAR017 production, the subject may have subsequent procedure(s) performed (see 8.2.3.1).
Table 3:
Washout Periods Prior to Leukapheresis
Drug
Washout
Alemtuzumab
6 months
Fludarabine
3 months
Cladribine
3 months
Radiation, multiple lesions
6 weeks
Experimental agents
4 weeks; or if no response or disease 
progression, then at least 3 half-lives 
Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, 
ifosfamide, bendamustine)
2 weeks
Radiation, single lesion, if additional nonirradiated PET-positive lesions 
are present
2 weeks
Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone 
or equivalent)
7 days
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
Intrathecal (dexamethasone, methotrexate or cytosine arabinoside)
7 days
Leukapheresis should be scheduled as soon as possible after meeting eligibility requirements, in 
coordination with the Sponsor. Venous access is required for leukapheresis and should be 
determined according to institutional practice. The following assessments will be conducted:

CBC with differential on the day of leukapheresis (or within 24 hours prior). CBC 
must include an absolute lymphocyte count. 

Vital signs (before and after leukapheresis)

Cell collection through leukapheresis

Record all AE/SAEs related to protocol-mandated procedures and concomitant 
medications taken at that time
8.2.3.1.
Assessments Prior to Repeat Leukapheresis 
If needed, subjects may undergo additional leukapheresis procedures if JCAR017 was unable to 
be manufactured. Subjects must continue to meet screening eligibility requirements in 
Section 5.1 and Section 5.2 in order to have a repeat leukapheresis collected. However, it is not 
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
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necessary to repeat PET scans, MUGA/ECHO, or ECG assessments to confirm eligibility. 
Positron-emission tomography/computed tomography scans will need to be repeated following 
the administration of optional bridging chemotherapy.
8.2.4.
Pretreatment Evaluation (Prior to Lymphodepleting Chemotherapy)
Unless otherwise noted, pretreatment evaluations must be performed within 7 days prior to 
lymphodepleting chemotherapy. 
The following assessments will be conducted:

Confirm that the subject meets study eligibility criteria (see Section 5):

ECOG performance status assessment 

Height/weight

Physical examination 

Routine neurological exam

Mini-Mental State Exam (MMSE)

Vital signs 

12-lead ECG

ECHO or MUGA scan (must be repeated after any intervening cardiotoxic anticancer 
therapy)

Local laboratory assessments: 

Serum ß-HCG pregnancy test on all women of child-bearing potential (within 
48 hours prior to starting lymphodepleting chemotherapy.

Chemistries

CBC with differential 

Coagulation 

Inflammatory markers

Immunoglobulins

Diagnostic quality CT (with contrast) performed at the study site. Must be done 
within 6 weeks of the start of lymphodepleting chemotherapy, and must be done after 
any intervening anticancer therapy, as close as possible to the start of 
lymphodepleting chemotherapy. Not required if done at the study site for screening
within 6 weeks and no intervening anticancer therapy has been administered.

PET scan performed at the study site. Must be done within 6 weeks of the start of 
lymphodepleting chemotherapy, and must be done after any intervening anticancer 
therapy, as close as possible to the start of lymphodepleting chemotherapy. Not 
required if done at the study site for screening within 6 weeks and no intervening 
anticancer therapy has been administered.
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JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
51
Protocol 017007 Amendment 2.0: 17 Mar 2020

Research blood samples (see the 017007 laboratory manual for details):

RCL testing

PK by quantitative polymerase chain reaction (qPCR)

Viral vector sequence testing by qPCR

Biomarkers

Immunogenicity Assessment

Lumbar puncture or Ommaya reservoir tap for cerebrospinal fluid (CSF) assessment 
(required for subjects with suspected or confirmed CNS involvement only)

MRI of the brain (required for subjects with suspected or confirmed CNS 
involvement or if clinically indicated)

HRQoL questionnaires (QLQ-C30 and EQ-5D-5L) 

Record all AEs/SAEs related to protocol-mandated procedures and associated 
concomitant medications (see Section 6.5 and Section 9.4.1).
8.2.5.
Lymphodepleting Chemotherapy Through Day 29
8.2.5.1.
Criteria for Treatment
Subject eligibility criteria must be confirmed immediately prior to starting the first cycle of 
lymphodepleting chemotherapy. Low-dose chemotherapy or chemoimmunotherapy given after 
leukapheresis to maintain disease control must be stopped ≥ 7 days prior to lymphodepleting 
chemotherapy.
Lymphodepleting chemotherapy will be withheld if serum creatinine is > 1.5 times the age-
adjusted ULN OR calculated creatinine clearance (Cockcroft and Gault; 
 or 
radioisotope GFR is ≤30 mL/min. Delay of lymphodepleting chemotherapy of more than 
14 days requires discussion with the Sponsor and may require rescreening.
Subjects should not experience a significant worsening in clinical status compared to either 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 8.2.5.3).
8.2.5.2.
Lymphodepleting Chemotherapy (Approximately 5 Days Prior to JCAR017)
Upon notification from the Sponsor that JCAR017 will be available, lymphodepleting 
chemotherapy should be initiated so as to finish 2 to 7 days prior to JCAR017 administration. 
Subjects will receive 3 days of fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2).
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JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
52
Protocol 017007 Amendment 2.0: 17 Mar 2020
The recommended administration is as follows: 
1. The IV hydration is 1 L of 0.9% NaCl given at 500 mL/hr starting 2 hours prior to 
cyclophosphamide 
2. Fludarabine 30 mg/m2 IV over 30 minutes 

If creatinine clearance is 50 to 70 mL/min: reduce each daily dose of fludarabine by 
20%

If creatinine clearance is 30 to 49 mL/min: reduce each daily dose of fludarabine by 
40%

Fludarabine should not be administered to subjects with CrCl < 30 mL/min.

Creatinine clearance (estimated glomerular filtration rate [eGFR] by Cockcroft-Gault, 
refer to 
 is required within approximately 48 hours of lymphodepleting 
chemotherapy to assess the need to adjust the dose of fludarabine. Indirect calculation 
of CrCl should be performed using the Cockcroft-Gault formula 
 Direct 
measurement of creatinine CrCl clearance is also acceptable.
3. Cyclophosphamide 300 mg/m2 IV over 60 minutes
4. Additional 1 L of 0.9% NaCl given at 500 mL/hr
The following assessments will be performed on each day before administration of 
lymphodepleting chemotherapy:

Vital signs

Local laboratory assessments:

Chemistries 

ECOG performance status (see 

Record all AE/SAEs and concomitant medications (before, during, and after 
administration)
Antiemetic therapy may be given prior to lymphodepleting chemotherapy per institutional 
practice. Mesna may be used for subjects with a history of hemorrhagic cystitis per institutional 
practice.
8.2.5.3.
Criteria for JCAR017 Treatment
Subject eligibility criteria must be confirmed immediately prior to administering JCAR017.
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 AEs 
associated with JCAR017 infusion. Subjects who meet at least 1 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
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
53
Protocol 017007 Amendment 2.0: 17 Mar 2020

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 6.6.

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 6.3).
In the event that a subject experiences any of the above, the Sponsor must be contacted and 
discussion regarding delay of treatment must occur.
8.2.5.4.
JCAR017 Administration–Day 1 (2 to 7 Days after Completion of the Last Dose 
of Lymphodepleting Chemotherapy)
JCAR017 should be delivered in an outpatient setting. At the Investigator’s discretion, treatment 
can be delivered in an inpatient setting for the following types of subjects (see Outpatient 
Guidelines for further details): 

Subjects who do not have adequate caregiver support

Subjects who are staying more than 60 minutes from the clinical trial site at the time 
of treatment

Subjects with disease characteristics that, in the Investigators’ clinical judgement, 
puts the subject at higher risk of complications (eg, TLS) 

Subjects with a psychosocial condition that puts them at risk for not following 
instructions
If changes to the JCAR017 manufacturing process are made, the Sponsor may mandate that 
subjects are treated in an inpatient setting until safety is confirmed.
Subjects must meet the criteria for treatment specified in Section 8.2.5.3. 
The following evaluations will be performed before JCAR017 administration as indicated in the 
Schedule of Evaluations (see 

Physical examination

Weight

ECOG performance status assessment
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
54
Protocol 017007 Amendment 2.0: 17 Mar 2020

Routine neurological examination

MMSE 

Clinical laboratory evaluations

Chemistries

CBC with differential count

Coagulation

Inflammatory markers

Research blood samples (see the 017007 laboratory manual):

PK by qPCR

B-cell enumeration

Viral vector sequencing by qPCR

Biomarkers

HRQoL

Vital signs: will be measured within approximately 5 minutes (± 5 minutes) before 
and approximately every 15 minutes thereafter for the first hour and hourly (± 15 
minutes) for the next 2 hours. Continue to monitor vital signs after this point until 
stable and as clinically indicated (see Section 8.3.3).

Premedication: subjects should be premedicated with 650 mg acetaminophen by 
mouth (PO) and 25 to 50 mg diphenhydramine hydrochloride (PO or IV), 30 to 
60 minutes prior to JCAR017 administration. In case a subject cannot tolerate 
diphenhydramine, an equivalent antihistamine may be substituted.  These medications 
may be repeated every 6 hours as needed based on the Investigator’s assessment of 
symptoms. Premedication with steroids is not allowed (see Section 6.6).

JCAR017 administration (2 to 7 days after completion of lymphodepleting 
chemotherapy)
8.2.5.5.
Day 2 through Day 29
Evaluations will be performed as indicated in the Schedule of Evaluations (see Appendix A).
Subjects can be followed in the outpatient setting after JCAR017 administration; however, they 
will require closer oversight for at least the first week. Subjects who have a high baseline tumor 
burden or high serum lactate dehydrogenase (LDH; ≥500 U/L prior to the start of 
lymphodepletion) have a higher risk for developing CRS and/or NT and should be closely 
monitored (see Section 7).
Subjects who are not appropriate candidates for outpatient monitoring include (see Outpatient 
Guidelines for further details): 

Subjects who do not have adequate caregiver support
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Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
55
Protocol 017007 Amendment 2.0: 17 Mar 2020

Subjects who are staying more than 60 minutes from the clinical trial site at the time 
of treatment (Day 2 to Day 29)

Subjects with disease characteristics that, in the Investigators’ clinical judgement, 
puts the subject at higher risk of disease-related complications (eg, TLS)

Subjects with a psychosocial condition that puts them at risk for not following 
instructions
From Day 2 to Day 29, subjects will monitor their body temperature and record the value in a 
patient diary. Subjects will be instructed to take their body temperature 3 times per day 
(approximately every 6 to 8 hours) and at any time that they feel a subjective increase in body 
temperature and/or experience chills. In the event of a temperature of ≥ 38.0°C (100.4°F),
subjects will be instructed to contact the study site immediately and seek medical evaluation.
Sites will monitor patients at least daily for 7 days (Day 2 to Day 8) by phone or with a clinic 
visit following administration for signs and symptoms of CRS and NT.
If subjects develop neurologic symptoms suspicious of and/or diagnosed as neurologic toxicity, 
subjects will have daily MMSE exams (see 
until resolution of symptoms, unless the 
subject is medically incapacitated and/or medically unable to complete the MMSE. 
8.2.6.
Follow-up Period: Through Month 24
All subjects, including subjects who withdraw from treatment early and those with PD, will 
complete the post-treatment follow-up visits at approximately Months 2, 3, 6, 9, 12, 18, and 24 
after the JCAR017 treatment for evaluation of safety, disease status, and survival. 
Evaluations will be performed as indicated in the Schedule of Evaluations (see Appendix A). 
8.2.7.
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 
 If subjects develop neurologic symptoms suspicious of 
and/or diagnosed as neurologic toxicity, subjects will have daily MMSE exams until 
resolution of symptoms, unless the subject is medically incapacitated and/or 
medically unable to complete the MMSE (see Section 8.3.3)

Clinical laboratory evaluations

PET scan

CT/ magnetic resonance imaging (MRI) scan

CSF assessment (see the 017007 laboratory manual)
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EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
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A Celgene Company
Confidential and Proprietary
56
Protocol 017007 Amendment 2.0: 17 Mar 2020

Research blood samples (see the 017007 laboratory manual):

PK by qPCR

Viral vector sequencing by qPCR.

Biomarkers

RCL
Additionally, if the Investigator requests any of the following procedures, research samples will 
be requested:

CSF assessment

Pleural, peritoneal, or other relevant fluid sampling

Tissue sampling

Autopsy
8.2.8.
Assessments on Disease Progression/Relapse
The following assessments will be performed as soon as possible after disease 
progression/relapse:

PET scan to confirm disease progression

Bone marrow aspirate and biopsy, as clinically indicated (see the 017007 laboratory 
manual) 

Tumor biopsy, as clinically indicated (see the 017007 laboratory manual)

HRQoL questionnaires (see Section 8.3.13)

Research samples (see Section 8.2.7 and the 017007 laboratory manual)

PK by qPCR

B-cell enumeration

Viral vector sequencing by qPCR

Biomarkers
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 (see Section 8.3.1.1).
Any subsequent anticancer therapies administered for disease progression will be recorded as 
concomitant medications while the subject remains in long-term follow up, as described in 
Section 6.5. The results of any standard-of-care disease response assessments after these 
subsequent therapies will be collected as an unscheduled visit; this is part of the long-term follow 
up of disease status for 24 months after JCAR017 treatment (see Section 8.2.10).
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Protocol 017007 
A Celgene Company
Confidential and Proprietary
57
Protocol 017007 Amendment 2.0: 17 Mar 2020
8.2.9.
Assessments in Subjects who Undergo Leukapheresis but Do Not Receive 
Treatment
The date of death for subjects who undergo leukapheresis but do not receive any further 
treatment on study should be collected in the eCRF.
8.2.10.
Long-term Follow-up
Because this protocol involves gene transfer, post-treatment follow-up for lentiviral vector 
safety, disease status, and long-term survival will continue on this protocol until 24 months after 
JCAR017 treatment, regardless of disease status, and under a separate LTFU protocol for up to 
15 years after JCAR017 treatment. 
All subjects who either complete the post-treatment follow-up period specified in this protocol or 
who prematurely withdraw after a dose of JCAR017 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 discontinue early from this study and do not 
consent to participate in the LTFU protocol will be followed for survival through public record
until their projected end of study visit.
8.2.11.
Second Primary Malignancies Follow-up Period
Second primary malignancies will be monitored as events of interest and must be reported as 
serious adverse events. This includes any new malignancies, regardless of causal relationship to 
JCAR017, occurring throughout the subject’s entire participation in the study. If a subject 
develops a second primary malignancy, the Sponsor will request that a tumor sample (refer to 
017007 laboratory manual) and blood samples are collected (See also Section 8.3.12.2 and
Section 8.3.12.6).
8.3.
Study Assessments
All study assessments should be performed at the times indicated in the Schedule of Evaluations 
in Appendix A.
8.3.1.
Efficacy Assessments 
Treatment response will be assessed by radiographic tumor evaluation at protocol-specified 
timepoints by diagnostic quality (with contrast) CT scans (chest, neck, abdomen, and pelvis) and 
PET scans. PET scans are not required after a subject achieves a CR unless progression is 
suspected on follow-up CT. Confirmation of PD and assessment of bone marrow involvement by 
lymphoma will be by PET scan only; bone marrow aspirates and biopsies will not be required for 
assessment of disease response. Upon documentation of disease progression or treatment with 
additional anticancer therapies, radiographic tumor evaluation is no longer required (Note, PET 
and CT scans will be read locally). Disease response will be determined according to the 
“Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and 
Non-Hodgkin Lymphoma: The Lugano Classification” (Cheson 2014) as described in 
as well as other pertinent clinical data, as appropriate.
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Protocol 017007 
A Celgene Company
Confidential and Proprietary
58
Protocol 017007 Amendment 2.0: 17 Mar 2020
8.3.1.1.
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 2014).
8.3.2.
Physical Examination
A physical examination should include assessments of the following body parts/systems: 
abdomen, extremities, cardiovascular, pulmonary, neurological (see Section 8.3.3) and lymph 
node examinations. In addition, symptom-directed examinations should be performed. 
8.3.3.
Routine Neurological and Mini-Mental State Examinations
A routine neurological exam should include, at minimum, a physical exam to assess cranial 
nerves, motor and sensory skills, coordination and balance (see 
 In the event a 
subject experiences neurotoxicity, a Mini Mental State Examination (MMSE) should be done at 
time of onset of neurotoxicity and then daily until resolution of symptoms, unless the subject is 
medically incapacitated and/or medically unable to complete the MMSE. The MMSE may be 
administered by an appropriately trained provider (ie, physician, nurse); a neurologist is not 
required. Efforts should be made to have the same provider perform the MMSE on a given 
subject to maintain consistency of assessment.
8.3.4.
Vital Signs
Vital signs include temperature, respiratory rate, heart rate, blood pressure, and SaO2 by pulse 
oximetry.
In addition, subjects will be required to monitor their body temperature at home and record it in a 
patient diary as described in Section 8.2.5.5.
8.3.5.
Tumor Biopsy
At the time of disease progression or relapse if a tumor biopsy was obtained locally as part of 
standard-of-care procedures and tissue remains available, then either unstained slides cut from a 
FFPE block or the FFPE block itself will be submitted to the central laboratory.
If a subject develops a new or recurrent neoplasm other than the study indication, the 
Investigator will inform the Sponsor and, if available, collect a sample of the neoplastic tissue for 
assessment of RCL.
8.3.6.
Adverse Events 
Adverse events will be collected as described in Section 9.
8.3.7.
Clinical Laboratory Evaluations
Screening and other laboratory evaluations (see Table 4) will be performed according to 
Appendix A. Additional assessments should be performed between scheduled study visits as 
clinically required in order to diagnose and monitor AEs. See Section 9.3.2 for laboratory 
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A Celgene Company
Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
abnormality AE reporting rules. The Investigator may choose to repeat any abnormal test in 
order to rule out laboratory or sample collection error.
Table 4:
Analytes for Clinical Laboratory Evaluations
Laboratory Panel
Analytes
Chemistries
Glucose (fasting or nonfasting), BUN, creatinine, sodium, potassium, 
β2-microglobulin, chloride, calcium, total protein, albumin, total and direct 
bilirubin, alkaline phosphatase, ALT (SGPT), AST (SGOT), magnesium, 
phosphate, CO2, LDH, uric acid, triglycerides
Hematology
CBC with differential (manual or automated)
Coagulation
PT/aPTT, INR, fibrinogen, and D-dimer
Viral Serology 
HIV
Hepatitis B (HBsAb, HBsAg, and HBcAb)
Hepatitis C (Hep C antibody)
Serum Pregnancy
Serum ß-hCG pregnancy test
Inflammatory Markers
CRP, ferritin
Serum Immunoglobulins
IgG, IgM, IgA
CSF (if clinically indicated)
Protein, cell counts, glucose
ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; 
ß-hCG = ß subunit of human chronionic gonadotropin; BUN = blood urea nitrogen; CBC = complete blood count; 
CRP = C-reactive protein: CSF = cerebrospinal fluid; HBcAb = hepatitis B core antibody; Hep C = hepatitis C virus; 
HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; CRP = C-reactive protein; HIV = 
human immunodeficiency virus; IgA, G, M = immunoblobulins A, G, and M; INR = international normalized ratio; 
LDH = lactate dehydrogenase; PT = prothrombin time; SGOT = serum glutamic oxaloacetic transaminase; SGPT = 
serum glutamic pyruvic transaminase.
8.3.8.
ECOG Performance Status
ECOG performance status (see 
 will be used to evaluate subject eligibility at 
screening as specified in Appendix A.
8.3.9.
MUGA/Echocardiogram
An assessment of LVEF will be performed by echocardiogram or MUGA to assess the cardiac 
function of the subject and to confirm study eligibility.
8.3.10.
Electrocardiogram
A standard 12-lead ECG should be obtained. ECG tracings should be labeled with the study 
number, subject number, date, and Investigator’s signature, and kept with the source documents 
at the study site.
8.3.11.
Cerebrospinal Fluid Examination and Central Nervous System Symptom 
Assessment
Cerebrospinal fluid assessments and CNS imaging (MRI or CT) should be performed before and 
after JCAR017 administration for subjects with suspected or confirmed CNS involvement, and 
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A Celgene Company
Confidential and Proprietary
60
Protocol 017007 Amendment 2.0: 17 Mar 2020
as clinically indicated (eg, if new CNS symptoms occur, or if clinical signs or suspicion of CNS 
involvement by lymphoma exists).
Cerebrospinal fluid will be analyzed locally for cell count and differential cytology, and centrally 
for the presence of JCAR017 (see the 017007 laboratory manual for instructions on sending a 
sample for JCAR017 testing). CSF cultures (bacterial, fungal, viral) should be performed as 
clinically indicated for suspicion of infection. 
 
8.3.12.
Pharmacokinetic, Pharmacodynamic, and Biomarker Assessments
Testing and analysis of the samples will, generally, follow the Schedule of Evaluations in 
Appendix A. Allocation of samples to specific testing may be modified where sample material is 
limited; however, the total volume and type of material collected will not be modified beyond 
what is described in the laboratory manual.
Detailed information regarding the collection, handling, and shipment of samples for PK, 
pharmacodynamics, biomarker and immunogenicity assessments are provided in the 017007 
laboratory manual.
8.3.12.1.
Pharmacokinetic Assessments
JCAR017 PK in blood (and bone marrow, when available) will be assessed by qPCR.
8.3.12.2.
Viral Vector Sequence Testing
Details regarding sample collection and processing are provided in the 017007 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 Month 
12 visit or later test positive for vector sequences, the pattern of vector integration sites will be 
analyzed. If a predominant integration site is detected, then the subject will be asked to provide 
another blood draw 3 months later for follow-up testing.
If a subject develops disease recurrence or a SPM, the Sponsor will request a sample of the 
neoplastic tissue (see 017007 laboratory manual), and an unscheduled peripheral blood draw for 
RCL and viral vector sequence testing (see also Section 8.2.11).
8.3.12.3.
Pharmacodynamic Assessments
Peripheral blood B-cell counts will be assessed to determine how JCAR017 impacts normal 
CD19+ B cells. In addition, levels of serum immunoglobulins will be monitored as another 
method to determine how normal B cells respond to treatment.
8.3.12.4.
Biomarker Assessments
Biomarker assessments may be performed to evaluate JCAR017, tumor, and immune system 
characteristics that may be associated with JCAR017 safety and efficacy. The focus of these 
assessments would be to supplement biomarker findings discovered in previously conducted 
trials (eg, TRANSCEND NHL001) with JCAR017. These assessments may include cytokines 
and chemokines associated with CRS and NT, immune cell function, and tumor and tumor 
microenvironment characterization (only if a tumor biopsy is being obtained for clinical 
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Confidential and Proprietary
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Protocol 017007 Amendment 2.0: 17 Mar 2020
purposes). Immunophenotypic and/or functional evaluation of JCAR017 and enumeration of 
immune cell subsets may also be performed. Peripheral blood and CSF (only if a lumbar 
puncture is indicated for clinical purposes) will be collected and banked for these evaluations.
Cytokines and chemokines may be measured in serum, plasma, and CSF (as available) as 
markers of immune activation. Potential correlations between cytokine/chemokine production 
and efficacy and severity of CRS and NT will be assessed. 
Immunoregulatory pathways operative in the tumor microenvironment may influence the fate 
and function of adoptively transferred JCAR017 T cells. If a tumor biopsy is being obtained for 
clinical purposes and there is available tissue, assessment of specific cellular elements within the 
tumor and the tumor microenvironment will be performed on biopsy samples to correlate the 
presence of these factors with response, duration of response and/or JCAR017 persistence and 
function. This will include evaluation of JCAR017 infiltration and prevalence, markers of 
JCAR017 phenotype and function, and location of JCAR017 relative to CD19+ tumor cells. 
Immunosuppressive biomarkers on other cell types in the tumor microenvironment may also be 
assessed.
Flow cytometry will be performed to characterize the expansion and persistence of JCAR017
CAR T-cell subsets and to enumerate immune cell subsets in the blood, and if applicable, bone 
marrow and CSF. Analyses to detect tumor cells in peripheral blood and to analyze tumor cells 
by flow cytometry may also be performed. These studies aim to identify cellular markers 
associated with JCAR017 persistence as well as safety and efficacy. 
Molecular profiling assessments, including single nucleotide polymorphism (SNP), ATACseq, 
AbSeq, targeted mutational analysis, whole exome/genome sequencing, and/or gene expression 
analysis (eg, RNA-Seq) may be conducted on JCAR017 cells, PBMCs and tumor cells in order 
to identify markers or signatures associated with clinical outcomes. Samples will be obtained 
pre-treatment, or isolated from peripheral blood, bone marrow aspirates, or tumor biopsies post-
treatment as available.
Peripheral blood and tumor biopsies will be collected for these studies at the timepoints indicated 
in Appendix A.
Detailed information regarding the collection, handling, and shipment of biomarker samples is 
provided in the 017007 laboratory manual.
8.3.12.5.
Immunogenicity Assessments
Immune responses to JCAR017 will be evaluated with an anti-therapeutic antibody (ATA) assay 
(plasma) to detect the presence of antibodies that bind to the extracellular region of JCAR017.  
In addition, cellular immunogenicity may be evaluated by testing PBMCs from subjects for the 
presence of anti-JCAR017 cytotoxic T cells.
8.3.12.6.
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, if available. Details regarding 
sample collection and processing are provided in the 017007 laboratory manual. Testing for RCL 
will use a polymerase chain reaction-based assay. Samples for RCL testing will be collected at 
the timepoints specified in Appendix A.
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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 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. Any confirmed positive result from RCL testing will be reported as an SAE within 
24 hours of the investigator being notified, and as an adverse experience in the form of an 
Investigational New Drug (IND) application safety report.  Other relevant health authorities will 
be notified of the detected RCL in accordance with local guidelines.
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 second primary malignancy, the Sponsor will request a sample of the 
neoplastic tissue (see 017007 laboratory manual), and an unscheduled peripheral blood draw for
RCL and viral vector sequence testing (see Section 8.2.11).
8.3.13.
Health-Related Quality of Life and Health Economics and Outcomes Research
Quality-of-life outcomes will be assessed using the European Organization for Research and 
Treatment of Cancer (EORTC) QLQ-C30 and the EuroQol instrument EQ-5D-5L. Subjects 
should, whenever possible, complete the questionnaires at the initiation of study visit, prior to 
any procedure or clinical evaluation. For subjects that do not complete the questionnaire at any 
given timepoint, reason for not collecting will be recorded (eg, too sick/unable to complete, 
administration error, subject refusal). 
If the subject withdraws from the study prematurely, all attempts should be made to obtain final 
quality-of-life questionnaires prior to subject discontinuation.
8.3.13.1.
EORTC QLQ-C30
The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item 
measures. All of the scales and single-item measures range in score from 0 to 100. A higher scale 
score represents a higher level of well-being and better ability of daily functioning. Thus, a high 
score for a functional scale represents a high/healthy level of functioning; a high score for the 
global health status/HRQoL represents a high HRQoL, but a high score for a symptom scale/item 
represents a high level of symptomatic problem.
8.3.13.2.
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, 
and anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate 
problems, severe problems, and extreme problems).
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8.3.14.
Hospital Resource Utilization
Hospital resource utilization will be assessed based on the numbers of ICU inpatient days and the 
number of non-ICU inpatient days. Dates of and reasons for admission and discharge to the 
hospital and to the ICU will be collected on the appropriate eCRF. The number of subjects 
requiring packed red blood cell or platelet transfusions, the number of transfusions per subject, 
the number of subjects requiring growth factor support, and the number of subjects requiring 
IVIG support will be summarized from the information gathered on the appropriate eCRF.
9.
SAFETY MONITORING AND REPORTING
9.1.
Definitions
9.1.1.
Adverse Event
In accordance with the International Council for Harmonisation (ICH) E2A guideline, and 
21 Code of Federal Regulations (CFR) §312.32, an AE is defined as any untoward medical 
occurrence in a clinical study subject administered a pharmaceutical product which does not 
necessarily have a causal relationship with this treatment.
9.1.2.
Serious Adverse Event
An SAE is defined as an event that, at any dose, meets any of the criteria in Table 5. Special 
considerations for SAE reporting are presented in Table 6.
Table 5:
Definitions of Serious Adverse Events
Criteria
Description
Fatal:
The AE resulted in death
Life-threatening:
The AE placed the subject at immediate risk of death (This classification does 
not apply to an AE that hypothetically might have caused death if it had been 
more severe).
Hospitalization/prolongation of 
Hospitalization:
The AE resulted in hospitalization or prolongation of hospitalization (See 
Table 6 below).
Disability/incapacity:
The AE resulted in a disability, significant incapacity, or substantial disruption 
of the subject’s ability to conduct normal life functions
Congenital Anomaly/birth 
Defect:
The AE was an adverse outcome in a child or fetus of a subject exposed to the 
study treatment regimen before conception or during pregnancy
Medically Important:
The AE was a medically important event that did not meet any of the above 
criteria, but may have jeopardized the subject and may have required medical 
or surgical intervention to prevent 1 of the outcomes listed above (examples 
include allergic bronchospasm that required treatment in an emergency room, 
seizures that do not result in hospitalization, or blood dyscrasias)
AE = adverse event.
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Table 6:
Special Considerations for SAE Reporting 
Criteria
Description
Hospitalization/prolongation of 
hospitalization
Note: complications and/or 
prolonged admissions for 
routine treatment or procedures 
do require SAE reporting
This classification does not apply for the following hospitalizations:

Admissions for social or situational reasons (eg, no place to stay, live too 
far away to come for hospital visits) in the absence of any clinical AE

Admissions at the discretion of the investigator for administration of 
lymphodepleting chemotherapy or JCAR017

Admissions for elective or preplanned treatment for a pre-existing 
condition that is unrelated to the condition under study and has not 
worsened since providing informed consent

Admissions for routine treatment (eg, platelet transfusion) or monitoring 
of the condition under study not associated with any deterioration in 
condition

Admissions for routine procedures (eg, bone marrow aspiration) 
associated with the disease under study 

Emergency outpatient treatment or observation that does not result in 
admission, unless fulfilling other seriousness criteria above
AE = adverse event; EOS = end of study; FDA = Food and Drug Administration; SAE = serious adverse event.
9.1.3.
Adverse Events of Special Interest
An AESI (serious or nonserious) is one of scientific and medical concern specific to the 
Sponsor’s product, for which ongoing monitoring and rapid communication by the Investigator 
to the Sponsor can be appropriate. Such an event might warrant further investigation in order to 
characterize and understand it.
Adverse events of special interest may include, but are not limited to, CRS, NT, prolonged 
cytopenia, Grade ≥ 3 infections, TLS, MAS, infusion reactions, hypogammaglobulinemia,
autoimmune disorders, and second primary malignancies (see 
for CRS/NT). These 
events have been identified as potential risks associated with JCAR017 treatment as well as other 
CAR T-cell therapies. Details of the AESIs definitions are provided in the SAP.
Prolonged cytopenia (laboratory values), is defined as the occurrence of Grade ≥3 cytopenia not
resolved by the Day 29 visit, based on laboratory results of low hemoglobin, absolute neutrophil 
count decreased, and platelet count decreased. The frequency of subjects experiencing each 
individual laboratory abnormality and the total number with at least 1 abnormality will be 
summarized, as will recovery from prolonged cytopenia after Day 29. 
9.1.3.1.
Grading and Intensity of Adverse Events
Adverse events, with the exception of CRS, will be graded using the CTCAE, Version 4.03
(https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm). CRS will be 
graded according to the grading scale adapted from Lee (Lee 2014), 
 
The reported verbatim term should be the most descriptive medical diagnosis, even if it does not 
match the CTCAE term used for assigning severity.
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AE severity and seriousness will be assessed independently. ‘Severity’ refers to the intensity of 
an AE, while ‘serious’ is a regulatory definition and serves as a guide to the Sponsor for defining 
regulatory reporting obligations.
9.2.
Relationship to Study Drug
The assessment of the relationship of an AE/SAE to lymphodepleting chemotherapy and 
JCAR017 (related or not related) is a clinical decision based on all available information and the 
following considerations:
Related:
There is a reasonable possibility and/or evidence to suggest a causal relationship 
between the study drug and the AE/SAE and no other more likely alternative 
cause (concomitant drugs, therapies, disease complications, etc.) is suspected.
Not 
related:
There is no reasonable possibility and/or evidence to suggest a causal relationship 
between study drug and the AE/SAE and another more likely alternative cause 
(concomitant drugs or therapies, disease complications, etc.) is suspected.
9.3.
Recording Adverse Events 
Adverse events/SAE are recorded on the eCRF in accordance with the reporting criteria for 
different time periods as defined in Section 9.4. Each AE/SAE is to be evaluated for:

Duration (onset and resolution dates) 

Severity, including grade changes during the 90-day period following JCAR017
administration, as per the eCRF completion guidelines (see Section 9.1.3.1)

Outcome 

Seriousness (see Section 9.1.2)

Causal relationship with lymphodepleting chemotherapy or JCAR017 (see 
Section 9.2)
9.3.1.
Recording a Diagnosis versus Signs and Symptoms
Whenever possible, a unifying diagnosis should be reported, as opposed to a listing of individual 
symptoms. However, symptoms should be grouped into a diagnosis only if each sign or symptom 
is a medically confirmed component of that diagnosis as evidenced by current standard medical 
textbooks. If any aspect of a sign or symptom does not fit into a classic pattern of the diagnosis, 
the individual symptom should be reported as a separate AE/SAE.
One exception to reporting a diagnosis as opposed to symptoms is the event of CRS. If a subject 
experiences an event of CRS, a diagnosis of CRS and any grade changes for the event of CRS 
should be reported as an AE. Individual signs and symptoms of CRS and grade changes for those 
signs and symptoms should be entered as CRS Symptoms in the eCRF. 
When manifestations of neurological toxicities appear in the presence of CRS or alone, those 
manifestations should be reported as separate AEs.
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9.3.2.
Clinical Laboratory Abnormalities and Other Abnormal Assessments
Any laboratory abnormality (eg, clinical chemistry or hematology) or other abnormal assessment 
findings (eg, ECG or vital signs) that meets any of the following criteria should be recorded as an 
AE or SAE:

Requires medical or surgical intervention (including transfusions or growth factors)

Leads to product discontinuation, delay, or interruption

Associated with clinical signs and/or symptoms

Otherwise clinically significant as determined by the Investigator
The clinical diagnosis, rather than the laboratory result or CTCAE, should be reported by the 
Investigator (eg, anemia versus low hematocrit; neutropenia versus neutrophil count decreased). 
9.3.3.
Recording Serious Adverse Events
The following should be considered when recording SAEs:

Death is an outcome of an event. The event that resulted in death should be recorded 
in the eCRF and reported on the SAE Report Form.

For hospitalizations for surgical or diagnostic procedures, the illness leading to the 
surgical or diagnostic procedure should be recorded as the SAE, not the procedure 
itself. 

When progression of the disease under investigation meets any of the seriousness 
criteria, it will be reported as an individual SAE. When reporting SAE terms related 
to disease progression, specific manifestations of the progression (eg, “malignant 
pleural effusion,” “lymphadenopathy from underlying non-Hodgkin lymphoma”) 
should be reported, rather than the general term “disease progression.”
9.3.4.
Death Reports
All deaths must be reported on the Death eCRF. Deaths due to PD will not be reported as an 
SAE unless considered related to a study drug.
Any AEs leading to death from the time the subject provides informed consent through 90 days 
after the JCAR017 infusion should be reported according to Table 7.
Deaths that occur more than 90 days after JCAR017 infusion will be captured on the Death 
eCRF and reported as an SAE only if considered related to any study procedure or JCAR017.
9.3.5.
Safety Queries
Queries pertaining to SAEs will be communicated from the Sponsor Drug Safety to the site via 
facsimile or electronic mail. The response time is expected to be no more than ten (10) business 
days. Urgent queries (eg, missing causality assessment) may be handled by phone.
9.3.6.
Pregnancy
All pregnancies or suspected pregnancies (including elevated βhCG or positive pregnancy test in 
a female subject of childbearing potential regardless of disease state) occurring at any time after 
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receipt of JCAR017, in a female subject or in the female partner of a male subject, must be 
reported to the Sponsor within 24 hours of learning of its occurrence 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.
Pregnancy follow-up, including all perinatal and neonatal outcomes, should be recorded on a 
Pregnancy Follow-up Form and should be submitted to the Sponsor within 24 hours of 
awareness. Any SAE experienced during pregnancy must be reported on the SAE Report Form. 
Abortion, whether accidental, therapeutic, or spontaneous, should be reported as an SAE. 
Congenital anomalies or birth defects, as defined by the “seriousness criteria” in Section 9.1.2, 
should be reported as SAEs.
In the event of a pregnancy occurring in a female subject of childbearing potential or female 
partner of a male subject, Celgene will additionally request information about the mother and 
child’s health during each trimester of pregnancy and for 1 year following the birth of the infant. 
Please reference the pregnancy information consent (permission) forms for data collection for 
additional information.
9.4.
Reporting Adverse Events to the Sponsor
9.4.1.
Reporting Periods for AEs and SAEs
Reporting periods for AEs and SAEs are summarized in Table 7.
Table 7:
Reporting Periods for AEs and SAEs
Reporting Period
What to Record/Report
Initial Informed Consent to first day of 
administration of lymphodepleting chemotherapy 
Only AEs/SAEs related to protocol-mandated procedures 
must be recorded/reported.
From first day of administration of 
lymphodepleting chemotherapy to 90 days 
following administration of JCAR017 or to EOS 
visit, whichever is earliera
All AEs and SAEs, irrespective of causality, must be 
recorded/reported.
For subjects starting a subsequent 
nonchemotherapy-containing anticancer therapy 
(eg, checkpoint inhibitors, IMIDs) prior to 90 
days following JCAR017 administration
All AE/SAEs will be collected after initiation of the 
subsequent therapy for 90 days following final JCAR017
infusion or 30 days following initiation of subsequent 
therapy, whichever is longer.
For subjects starting a subsequent chemotherapy-
containing anticancer therapy prior to 90 days 
following JCAR017 administration
Only AEs and SAEs related to JCAR017 and/or protocol-
mandated procedures must be recorded/reported after 
initiation of subsequent therapy.
From 91 days following administration of 
JCAR017 until EOS visit
All AEs and SAEs related to JCAR017 and/or protocol-
mandated procedures must be recorded/reported.
From 91 days following administration of 
JCAR017 or start of subsequent chemotherapy, 
whichever is first, to EOS visit 
The following conditions must be reported as SAEs, 
regardless of relationship to study drug: (as described in 
Table 6)

Second primary malignancies

New onset or exacerbation of a pre-existing neurologic 
disorder
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Reporting Period
What to Record/Report

New onset or exacerbation of rheumatologic or other 
autoimmune disorder

New onset hematologic disorder (eg, myelofibrosis)
Rare and unexpected disorders with and unknown etiology 
(eg, Guillain-Barré, Stevens-Johnson syndromes)
AE = adverse event; EOS = end of study; IMID = immune modulating imide drug; JCAR017 = autologous CD4+ 
and CD8+ T cells expressing a CD19-specific chimeric antigen receptor; SAE = serious adverse event.
a 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.
b Any clinically significant conditions/events unrelated to study procedures should be reported either in medical 
history or as an adverse event as described in the CCGs.
SAEs will be followed until they resolve or 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. All nonserious AEs will be followed through the safety reporting period. Certain 
nonserious AESIs may be followed until they resolve, return to baseline, or study closure. 
9.4.2.
Reporting Timelines for Serious Adverse Events
All SAEs must be reported 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 SAE form is completed in its entirety and that the 
data on the form is accurate and consistent. This requirement applies to all SAEs (regardless of 
relationship to investigational product) recorded in the CRF 
The SAE Report Form should provide a detailed description of the SAE and include a concise 
summary of hospital records, discharge reports, and other relevant documents. If a subject died 
and an autopsy was performed, copies of the autopsy report and death certificates are to be sent 
to Celgene Drug Safety as soon as these become available. If a subject develops a second 
primary malignancy, copies of the pathology and histology reports are to be sent to Celgene 
Drug Safety as soon as these become available.
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.
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 10 business days. 
Urgent queries (eg, missing causality assessment) may be handled by phone.
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10.
STATISTICAL METHODS
More details will be provided in a separate statistical analysis plan (SAP), which will be finalized 
prior to database lock.
10.1.
General Considerations
This study is designed for estimation and does not include formal hypothesis testing or 
adjustment for multiplicity. Data from all sites will be combined for the analysis. Data from 
subjects who received nonconforming product will be summarized separately.
10.2.
Analysis Sets
10.2.1.
Screened Set
The Screened Set will include all subjects who have signed informed consent.
10.2.2.
Eligible Set
The Eligible Set will include all subjects who have signed informed consent, and who meet all 
inclusion/exclusion criteria.
10.2.3.
Leukapheresed Set
The Leukapheresed Set includes subjects who undergo leukapheresis.
10.2.4.
JCAR017-treated Analysis Set
The JCAR017-treated Analysis Set will include all subjects who have received a dose of 
conforming JCAR017 cell product. 
10.2.5.
Outpatient Analysis Set
The Outpatient Analysis Set will include all subjects in the JCAR017-treated Analysis Set who 
are monitored as an outpatient. A subject is considered to be monitored as an outpatient if, 
following JCAR017 administration, the subject is monitored initially as an outpatient, regardless 
of JCAR017 administration setting.
10.2.6.
Pharmacokinetic Analysis Set
The PK Analysis Set includes subjects in the JCAR017-treated Analysis Set who have the 
necessary baseline and on-study PK measurements to provide interpretable results for the 
specific parameters of interest.
10.3.
Planned Analyses
10.3.1.
Subject Disposition and Baseline Characteristics
Descriptive summaries of demographics and baseline characteristics will be presented for the 
JCAR017-treated Analysis Set and the Outpatient Analysis Set. 
Available demographic and baseline information on such subjects will be listed and summarized.
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10.3.2.
Primary Endpoints
The primary endpoints of the study are:
1. Incidence of Grade ≥ 3 CRS, a syndrome which is characterized by high fever, fatigue, 
nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, 
and anorexia
2. Incidence of Grade ≥ 3 NT, defined as an Investigator-identified AE considered 
neurotoxicity related to JCAR017
3. Incidence of Grade ≥ 3 prolonged cytopenias (laboratory values), defined as the 
occurrence of Grade ≥ 3 cytopenias not resolved by the Day 29 visit, based on laboratory 
results of low hemoglobin, absolute neutrophil count decreased, and platelet count 
decreased. 
4. Incidence of Grade ≥ 3 infections, defined using Medical Dictionary for Regulatory 
Activities (MedDRA) system organ class (SOC) (Section 10.3.5.1). Analysis methods are 
described in Section 10.3.5. 
10.3.3.
Secondary Endpoints
The secondary endpoints of the study are:
1. Type, frequency, and severity of all AEs and laboratory abnormalities (see 
Section 10.3.5)
2. Incidence of any Grade ≥ 3 AEs (see Section 10.3.5)
3. Median time to onset and median time to resolution of Grade ≥ 3 CRS and NT (see 
Section 10.3.5)
4. Use of tocilizumab and glucocorticoids for management of CRS and NT (see 
Section 10.3.5)
5. ORR (see Section 10.3.6.1) 
6. CR rate (see Section 10.3.6.2)
7. DOR and duration of complete response (DoCR) following JCAR017 treatment (see 
Section 10.3.6.3)
8. Progression-free survival (PFS) and OS following JCAR017 treatment (see 
Section 10.3.6.4 and Section 10.3.6.5)
9. Maximum concentration (Cmax), time to peak concentration (Tmax), area under the 
curve (AUC), and other relevant PK parameters of JCAR017 in blood (see 
Section 10.3.7)
10. Measurement of HRQoL changes as assessed using the EORTC QLQ-C30 and the 
EuroQol instrument EQ-5D-5L (see Section 10.3.8) 
11. Number of ICU inpatient days and non-ICU inpatient days and reasons for hospitalization 
(see Section 10.3.8)
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If baseline data are missing, then any graded abnormality (ie, an abnormality that is Grade ≥ 1 in 
severity) will be considered treatment-emergent. Hematological and serum biochemistry data 
will be graded according to CTCAE Version 4.03, when applicable. Grade 0 includes all 
nonmissing values that do not meet the criteria for an abnormality of at least Grade 1. Grade 5 
will not be used. Some laboratory tests have criteria for both increased and decreased levels; 
analyses for each direction (ie, increased, decreased) will be presented separately. 
Prolonged cytopenia is defined in Section 9.1.3 and is not based on the definition of treatment-
emergent laboratory abnormalities. The frequency of subjects experiencing each individual 
laboratory abnormality and those with at least 1 abnormality on Day 29 will be summarized, as 
will recovery of prolonged cytopenia after Day 29.
10.3.5.3.
Safety Subgroup Analysis
In the JCAR017-treated Analysis Set, safety subgroup analyses will be performed for baseline 
tumor burden (measured by the sum of product of the perpendicular diameters (SPD) or high 
serum LDH prior to the start of lymphodepletion), age, and CNS disease status. These as well as 
additional subgroup analyses, which may be performed, will be described in the SAP prior to 
database lock. Subgroup analyses will only be performed if there are at least 5 subjects in each 
subgroup. Some grouping of classes will be considered if there are too few subjects in some 
subgroups. Other subgroup analyses will also be performed if deemed appropriate.  
10.3.5.4.
Safety Monitoring Boundaries
Safety monitoring boundaries based on Bayesian framework (Thall 1994) have been included to 
help detect signals that may occur in the study.  These boundaries are non-binding and the 
following toxicity events occurring within 30 days of a JCAR017 cell product infusion will be 
considered as safety events of interest for monitoring:

A Grade 3 or above, JCAR017-related, treatment-emergent neurological toxicity

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
Whenever the safety boundaries are crossed, enrollment will be paused and an ad hoc SRC
meeting will be held to review the data. The study will remain paused for enrollment pending the 
SRC recommendations. More information is available in the 017007 Statistical Analysis Plan
(SAP).
10.3.6.
Efficacy Analysis
Efficacy analyses will be based on the JCAR017-treated Analysis Set.
10.3.6.1.
Objective Response Rate 
The ORR analyses will be based on the JCAR017-treated Analysis Set, using Investigator 
assessments of disease status. The ORR is defined as the proportion of subjects with a best 
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overall response (BOR) of either a CR or PR. The BOR is the best disease response recorded 
from the time of the final JCAR017 infusion until disease progression, end of study, the start of 
another anticancer therapy, or HSCT. Best response will be assigned according to the following 
order: CR, PR, SD, PD, not evaluable, or not done.
10.3.6.2.
Complete Response Rate
The complete response rate is defined as the proportion of subjects with a BOR of CR following 
JCAR017 treatment. The CR rate will be assessed as described for ORR above.
10.3.6.3.
Duration of Response 
Duration of response and DoCR following JCAR017 treatment are each defined as the time from 
first response to PD or death. If a subject does not have an event for the DOR or DoCR analysis, 
the subject will be censored at the date of the last adequate disease assessments on or prior to the 
earliest censoring event. The censoring reasons can include ongoing follow-up, discontinuation 
or completion of the study, receipt of another anticancer treatment, and subsequent transplant. 
Kaplan-Meier methodology will be used to estimate DOR and DoCR.
10.3.6.4.
Progression-free Survival
Progression-free survival is defined as the time from infusion of JCAR017 to progressive disease 
or death, whichever is earlier. 
If a subject does not have an event for the PFS analysis, the subject will be censored at the date 
of the last adequate disease assessments on or prior to the earliest censoring event. The censoring 
reason can include ongoing follow-up, discontinuation or completion of the study, and receipt of 
another anticancer treatment. 
Kaplan-Meier methodology will be used to estimate PFS.
10.3.6.5.
Overall Survival 
Overall survival is defined as the time from infusion of JCAR017 to the date of death. If a 
subject does not have an event for the OS analysis, the subject will be censored on the date the 
subject is last known to be alive.
Kaplan-Meier methodology will be used to estimate OS.
10.3.6.6.
Efficacy Subgroup Analysis
In the JCAR017-treated Analysis Set, efficacy subgroup analyses may be performed on the same 
variables as specified in Section 10.3.5.3. Subgroup analyses will be performed for key safety 
summaries, and will only be performed if there are at least 5 subjects in each subgroup. Some 
grouping of classes will be considered if there are too few subjects in some subgroups. Other 
subgroup analyses will also be performed if deemed appropriate.
10.3.7.
Pharmacokinetic Analyses
Pharmacokinetic analyses will be performed based on the PK Analysis Set.
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The PK profile of JCAR017 cells in blood will be characterized, including Cmax, Tmax, AUC,
and other relevant PK parameters. The kinetics of expansion of JCAR017 in the blood will be 
determined, along with the persistence of JCAR017 in the blood, based on the qPCR assay.
Pharmacokinetic parameters of qPCR-based JCAR017 transgene concentration in peripheral 
blood versus time will be displayed graphically, where possible.
Pharmacokinetic parameters will be estimated from the individual concentration-time profiles 
using a noncompartmental analysis approach.
Descriptive statistics for PK parameters will be categorized by efficacy and safety parameters
and will include mean, standard deviation, coefficient of variation, minimum, and maximum. 
Median and ranges of values may be presented for selected variables.
Details of the pharmacokinetic analyses will be provided in the SAP or in a separate biomarker
analysis plan.
10.3.8.
Health-related Quality of Life and Health Economics and Outcomes Research
The analysis of HRQoL variables will include subjects who have baseline and at least 1 post-
baseline value in the JCAR017-treated Analysis Set. 
In the absence of a more specific hypothesis, the EORTC QLQ-C30 global health status score 
will be used as the primary HRQoL outcome with physical functioning and the fatigue symptom 
scale as secondary outcomes.
The EORTC QLQ-C30 and EQ-5D-5L will be analyzed according to the instrument-specific
scoring manual. Scores for both instruments will be descriptively tabulated (number, mean, 
standard deviation, median, 95% confidence interval) at each timepoint. Single items will be also 
described in terms of number and frequency. Change from baseline in HRQoL outcomes will be 
summarized using descriptive statistics.  Details will be given in the SAP.
Hospital resource utilization will be assessed based on the number of ICU and non-ICU inpatient 
days. The reasons for hospitalization, the number of subjects requiring packed red blood cell or 
platelet transfusions, the number of transfusions per subject, the number of subjects requiring 
growth factor support, and the number of subjects requiring IVIG support will be summarized. 
Descriptive statistics will be provided for subjects in the JCAR017-treated Analysis Set.
10.3.9.
Nonconforming Product
If there are subjects who received at least 1 dose of nonconforming JCAR017 cell product, then 
subject disposition and baseline characteristics, safety and efficacy will be summarized 
separately for these subjects. Additional analyses for subjects receiving nonconforming product 
may be performed and will be described in the SAP prior to database lock.
10.4.
Sample Size Considerations
Assuming a 30% drop out rate, a total of 114 subjects may be enrolled to ensure that 
approximately 80 subjects are treated with JCAR017, with a minimum of approximately 50 
treated subjects monitored as an outpatient.
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This study is designed for estimation and does not include formal hypothesis testing or 
adjustment for multiplicity. For any individual incidence rate (eg, AEs, ORR, CR), 80 subjects 
would provide a precision of ± 11.4% and 50 subjects would provide a precision of ± 14.5%, to 
estimate each endpoint assuming a confidence level of 95%. This is based on an event rate of 
50% using the exact Clopper-Pearson method. Other rates would have narrower confidence 
intervals.
In 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% confidence intervals are given in Table 8.
Table 8:
Example Rates (± 95% Confidence Intervals)
Rate
Sample Size
Expected Count
Lower 95% CI
Upper 95% CI
50%
80
40
38.6%
61.4%
38%
80
30
26.9%
49.0%
12%
80
10
6.2%
21.8%
9%
80
7
3.6%
17.2%
50%
50
25
35.5%
64.5%
38%
50
19
24.6%
52.8%
12%
50
6
4.5%
24.3%
9%
50
4
2.2%
19.2%
Abbreviations: CI = confidence interval.
10.5.
Timing of Analyses 
Interim data may be analyzed and presented at scientific meetings.
An analysis is anticipated after at least 80 subjects have been treated with JCAR017 and these 
subjects have been followed for at least 6 months or until death, PD, or withdrawal from study.  
Subjects treated with nonconforming product will not count towards the 80 subjects.
The final analyses will be carried out after all subjects have completed or discontinued the study 
due to any reason. No formal hypothesis testing will be performed for this study.
11.
DATA MANAGEMENT
11.1.
Data Collection System
An electronic data capture (EDC) system provided by the Sponsor will be used for data 
collection. The EDC system is a fully validated, secure system that conforms to 21 CFR Part 11 
requirements. Access to the EDC system is role-based, and login credentials will be provided 
only after completion of the assigned role-based training. 
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11.2.
Data Quality 
Study site personnel will enter data into the CRFs in the EDC system. The Sponsor Clinical 
Research Associate (CRA) or designee will verify data recorded in the CRFs with the source 
documents.
To ensure complete and accurate data, automated data validation checks programmed within the 
EDC system will flag missing and nonconformant data during data entry. Data review by the 
Sponsor project team may result in additional questions. Items flagged by the automated data 
validation checks and by the project team will appear as electronic queries on the applicable 
eCRF in the EDC system for a specified user role to resolve. All data entry and subsequent data 
changes are logged in an audit trail in the EDC system. 
The Principal Investigator is responsible for ensuring that the data entered into the CRFs are 
complete and accurate and will electronically sign the CRFs for each subject prior to database 
lock.
Following database lock, an electronic copy of the final subject casebook will be provided to the 
study site for archival.
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12.
STUDY ADMINISTRATION
12.1.
Regulatory and Ethical Considerations
12.1.1.
Regulatory Authority Review
The study will be conducted in accordance with Good Clinical Practice (GCP), the protocol, and 
any other applicable Federal, state, and/or local regulatory requirements.
12.1.2.
Institutional Review Board/Independent Ethics Committee Approval
It is the responsibility of the Investigator to ensure that the IRB has reviewed and approved this 
protocol prior to initiating the study. The IRB must also review and approve the investigative 
site’s ICF, other written information provided to the subject, and all subject materials that may 
be used. 
If the protocol, Investigator’s Brochure, or ICF are amended during the study, per local 
regulations the Investigator is responsible for ensuring that the IRB has reviewed and approved 
these amended documents. In addition, IRB approval of the amended documents must be 
obtained before implementation and before new subjects are consented to participate in the study 
using the amended version of the ICF. 
12.1.3.
Institutional Biosafety Committee Approvals
JCAR017 consists of autologous T cells that have been manipulated via genetic modification in 
vitro to express a CAR directed against the CD19 cell surface marker. Since neither the subject 
source material nor the final drug product has been tested for the presence of communicable 
diseases in accordance with the provisions in 21 CFR §1271.90(a)(1), the JCAR017 drug product 
should be handled according to institutional procedures for materials that may contain infectious 
materials (eg, Biosafety Level 1 or 2). 
It is the responsibility of the Investigator to ensure that the appropriate Institutional Biosafety 
Committee (IBC) has reviewed and approved this protocol, protocol amendments, and any other 
required materials prior to initiating the study if required per institutional policy. 
Each site will be approved by the IBC in accordance with local procedures and country-specific 
regulatory requirements. Documentation of IBC approval must be in place prior to JCAR017
shipment to the site.
12.1.4.
Subject Informed Consent
Prior to study entry, the Investigator, or a qualified person designated by the Investigator, will be 
responsible for explaining the nature, purpose, benefits, and risks of participation in the study to 
each subject, subject’s legally acceptable representative, or impartial witness. Written informed 
consent must be obtained prior to the subject entering the study (before initiation of any 
study-related procedure). Sufficient time will be allowed to discuss any questions raised by the 
subject. The Investigator or designated staff will document this process in the study records. The 
Investigator must use the current IRB -approved consent form for documenting written informed 
consent. Each informed consent form will be appropriately signed and dated by the subject or the 
subject’s legally authorized representative and the person conducting the consent discussion, and 
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also by an impartial witness if required by the IRB or local requirements. The process of 
obtaining the informed consent will be in compliance with all federal regulations, ICH 
requirements (ICH E6) and local laws.
If the ICF is amended during the study, the Investigator must follow all applicable regulatory 
requirements pertaining to approval of the amended ICF by the IRB. The investigative site must 
use the amended ICF for all new subjects and repeat the consent process with the amended ICF 
for any ongoing subjects.
12.2.
Investigator Obligations
12.2.1.
Investigator Responsibilities
The Investigator is responsible for ensuring that all study site personnel, including 
Sub-investigators and other responsible study staff members, conduct the study in compliance 
with the Declaration of Helsinki and the ICH E6 Guideline for GCP, including the archiving of 
essential documents.
The Investigator will ensure adherence to the basic principles of GCP, as outlined in 
21 CFR 312, Subpart D, “Responsibilities of Sponsors and Investigators,” 21 CFR, Part 50, 
1998, and 21 CFR, Part 56, 1998.
The Investigator, Sub-Investigators, and key study staff as listed on FDA form 1572 will comply 
with 21 CFR, Part 54, 1998, providing documentation of any financial conflict of interest. This 
documentation must be provided prior to the Investigator’s (and any Sub-Investigators) 
participation in the study. The Investigator and Sub-Investigator(s) agree to notify Juno 
Therapeutics of any change in reportable interests during the study and for 1 year following 
completion of the study at the Investigator’s site. Study completion at a site is defined as the date 
when the study database is locked. 
If necessary to amend either the protocol or the study ICF, the Investigator will be responsible 
for ensuring that the IRB reviews and approves the amended documents, and that subjects are 
informed of applicable changes, and updates.
The Investigator will sign and return to the Sponsor the “Protocol Signature Page” of the original 
protocol and any protocol amendment, provide current medical licenses, curriculum vitae, and 
the US FDA form 1572 “Statement of Investigator.” All forms must be updated as applicable 
throughout the study.
12.2.2.
Investigator Reporting Requirements 
In accordance with applicable regulatory requirements, the Investigator is solely obligated to 
inform the IRB of progress of the study and notify the IRB of study closure. The Investigator 
must also provide the Sponsor with copies of all IRB correspondence that relate to study 
approvals, updates, or changes. The Investigator must also forward all IRB renewals to Juno 
Therapeutics.
12.3.
Access to Information for Monitoring
Site monitoring is necessary to ensure that the rights and well-being of trial participants are 
protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
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of the trial is in compliance with the currently approved protocol/amendment(s), with ICH GCP, 
and with applicable regulatory requirement(s). In accordance with regulations and guidelines, the 
designated the Sponsor CRA must have direct access to the Investigator’s source documentation 
(including medical records, test and procedure results, investigator and study staff notes, etc.) in 
order to verify the accuracy of the data recorded in the eCRF.
The CRA is responsible for routine review of the CRFs at regular intervals throughout the study 
to verify adherence to the protocol and the completeness, consistency, and accuracy of the data 
being entered on them. The CRA should have access to any subject records needed to verify the 
entries on the CRFs. The Investigator agrees to cooperate with the CRA to ensure that any 
problems detected through any type of monitoring (central, on site) are resolved.
12.4.
Site Audits and Regulatory Inspections
Representatives of regulatory authorities or the Sponsor may conduct inspections or audits of the 
clinical study. If the Investigator is notified of an inspection by a regulatory authority, the 
Investigator agrees to notify the Juno Therapeutics Study Manager immediately. The Investigator 
agrees to provide to representatives of a regulatory agency or Juno Therapeutics access to 
records, facilities, and personnel for the effective conduct of any inspection or audit.
12.5.
Protocol Deviations
Protocol deviations must be sent to the IRB per their policies. The Investigator is responsible for 
knowing and adhering to the IRB requirements.
12.6.
Quality Assurance and Quality Control
The Sponsor or its designee will perform quality control and quality assurance checks of all 
clinical studies that it sponsors. Before the enrollment of any subject in this study, the Sponsor
personnel will review and provide training as needed to the Investigator, Sub-Investigators, and 
study site personnel regarding the following: protocol, IB, eCRFs and procedures for their 
completion, informed consent process, and procedures for reporting SAEs. Site visits will be 
performed by the Sponsor CRAs or designees periodically throughout the study. During these 
visits, information recorded on the eCRFs will be verified against source documents, and 
requests for clarification or correction may be made. The eCRFs will be reviewed by the CRA 
for safety information, completeness, accuracy, and logical consistency. Computer programs that 
identify data inconsistencies may be used to help monitor the clinical study. Requests for 
clarification or correction will be sent to Investigators via data queries.
12.7.
Public Notification of Study Conduct
Consistent with Section 113 of the Food and Drug Modernization Act of 1997 and with 
requirements of the International Committee of Medical Journal Editors as a condition of 
consideration for publication of study results, Juno Therapeutics will be responsible for ensuring 
that this protocol is listed at the ClinicalTrials.gov website per the US FDA requirement and that 
information at the website relating to study design and conduct is appropriately updated during 
the course of the study.  Outside the US, this study and its results may be submitted for inclusion 
in appropriate health authority study registries, as well as publication on health authority study 
registry websites, as required by local health authority regulations.
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12.8.
Study Completion
Upon completion or early termination of the study, the following activities, when applicable, 
must be conducted by the CRA and the Investigator:

Return of all electronic and any nonelectronic study data to the Sponsor, if requested;

Data clarifications and/or resolutions;

Accounting, reconciliation, and final disposition of used and unused study drug; and

Review of site study records for completeness.
In addition, the Sponsor reserves the right to temporarily suspend or prematurely terminate this 
study for any reason (see Section 4.5).
12.9.
Site Termination
The Sponsor has the right to terminate a study site at any time for various reasons. Study 
termination and follow-up will be performed in compliance with the conditions set forth in 
21 CFR Parts 312.50 and 312.56 and local regulations.
12.10.
Records Retention
The Investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. Records of subjects, 
source documents, monitoring visit logs, inventory logs of study drug product, regulatory 
documents, and other Sponsor correspondence pertaining to the study must be kept in the 
appropriate study files at the site. Source documents include all recordings and observations or 
notations of clinical activities and all reports and records necessary for the evaluation and 
reconstruction of the clinical study. This includes any electronic records. These records will be 
retained in a secure file for the period required by the institution or site policy but not less than 
25 years. Prior to the transfer or destruction of these records, Juno Therapeutics must be notified 
in writing and be given the opportunity to further store such records.
12.11.
Confidentiality of Information
Individual subjects and their research data will be identified by a unique study identification 
number. Subjects’ names will remain confidential and will not be included in the database. This 
confidentiality extends to testing of biological samples and genetic tests in addition to the clinical 
information relating to subjects. Therefore, the study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the study or 
the data will be released to any unauthorized third party without prior written approval of the 
Sponsor. The Investigator will maintain a personal subject identification list (subject numbers 
with the corresponding subject names) to enable records to be identified. 
For tracking purposes and product chain of custody, subjects’ name and name and date of birth 
will be communicated to the Sponsor’s scheduling and manufacturing staff. This information 
will also be listed on the leukapheresis cell collection bag, and other containers throughout the 
JCAR017 manufacturing process. This information will be maintained in a separate limited-
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13.
CONTACT INFORMATION
13.1.
Study Sponsor
Juno Therapeutics, Inc., a wholly-owned subsidiary of Celgene Corporation
400 Dexter Ave North, Suite 1200
Seattle, WA 98109
Phone: 
www.junotherapeutics.com
13.2.
Global Drug Safety
Celgene Corporation: 
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Turtle CJ, Riddell SR, Maloney DG. CD19-targeted chimeric antigen receptor-modified T cell 
immunotherapy for B cell malignancies. Clin Pharmacol Ther. 2016b Sep;100(3):252-8.
Vacirca JL, Acs PI, Tabbara IA, et al. Bendamustine combined with rituximab for patients with 
relapsed or refractory diffuse large B cell lymphoma. Ann Hematol 2013;93(3):403-9.
Van Den Neste E, Schmitz N, Mounier N, et al. Outcome of patients with relapsed diffuse large 
B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. 
Bone Marrow Transplant 2016;51(1):51-7.
Wang GP, Levine BL, Binder GK, et al. Analysis of lentiviral vector integration in HIV+ study 
subjects receiving autologous infusions of gene modified CD4+ T cells. Mol Ther 
2009;17(5):844-50.
Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or 
refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial.
Leukemia 2013;27(9):1902-9.
Yescarta®.[Prescribing Information]. Santa Monica, USA: Kite Pharma, Inc.; 2019. Available 
from: https://www.gilead.com/-/media/files/pdfs/medicines/oncology/yescarta/yescarta-pi.pdf
Ziepert M, Hasenclever D, Kuhnt E, et al. Standard international prognostic index remains a 
valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab 
era. J Clin Oncol 2010;28(14):2373-80.
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APPENDIX A. SCHEDULES OF EVALUATIONS
Screening:
88
Leukapheresis
88
Pretreatment through End of Study:
89
STUDY 017007: SCREENING ASSESSMENTS
Obtain Consent
x
Inclusion/Exclusion Criteria (5)
x
Medical History
x
ECOG 
x
Physical Examination (8.3.2)
x
12-lead ECG 
x
MUGA/ECHO 
x
Viral Serology (8.3.7)
x
Serum Pregnancy (8.3.7)
x
PET Scans(8.3.1)
xa
CBC with Differential (8.3.7)
x
Chemistries (8.3.7)
x
Pathology Reportb
x
Record all AEs/SAEs related to study procedures and concomitant medications 
taken at that time
x
Note: If a subject has had a screening procedure as standard of care within 30 days of consent, it may be used to 
evaluate study eligibility after discussion with the Sponsor.
AE = adverse event; CBC = complete blood count; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = 
Eastern Cooperative Oncology Group; MUGA = multiple uptake gated acquisition scan; PET = positron emission 
tomography; SAE = serious adverse event.
a PET scan may be performed more than 30 days prior to screening if no intervening anticancer treatments have 
been performed.
b For subjects with tDLBCL, a pathology report from the biopsy of their current relapsed disease is required.
AE = adverse event; ALC = absolute lymphocyte count; CBC = complete blood count; SAE = serious adverse event.
STUDY 017007: LEUKAPHERESIS ASSESSMENTS
CBC w/differential (8.3.7) on the day of (or within 24 hours prior to) leukapheresis. CBC must 
include ALC
x
Vital Signs (8.3.3), before and after leukapheresis
x
Leukapheresis (3)
x
Record all AEs/SAEs related to study procedures and concomitant medications taken at that time
x
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STUDY 017007: PRETREATMENT, TREATMENT, AND POST-TREATMENT ASSESSMENTS
Screening
Pre-
treatment 
Period
Treatment Period
Post-treatment
(Follow-Up, Disease Progression, EOS)
Note: efficacy evaluations (CT, PET) not 
required after PD or subsequent anticancer 
treatment
Study Day
Approxi-
mately 
1-2 Weeks 
Prior to 
Leuka-
pheresis
Within 
7 days Prior 
to Lympho-
depletion
Lympho-
depletion
Ending 
Day -7 to 
2f
1f
4
8
11
15
22
29
60
90
180
270
365
545
PD
730 
(EOS)
Month
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
2
3
6
9
12
18
N/A
24
Visit Window (days)
± 1
± 1
± 1
± 2
± 2
± 2
± 14
± 14
± 14
± 14
± 14
± 14
N/A
± 14
Procedure (protocol section)
Informed consent
x
I/E criteria (5)
x
x
x
Medical history
x
Pathology report*
x
ECOG (8.3.8)
x
x
x
x
Height/weight
x
xh
Physical examination (8.3.2)
x
x
x
xj
x
xj
x
x
x
xb
xb
xb
xb
x
xb
x
Routine neurological examination
(8.3.3)
x
x
x
x
x
x
x
x
x
xb
xb
xb
xb
x
xb
x
MMSE (8.3.3)
x
xv
xv
xv
xv
xv
xv
xv
xv
xb,v
xb,v
Vital signs (8.3.4)
x
xg
xi
x
x
x
x
x
x
Diary of daily temperature 
recording
(Subject to monitor temperature at home 
3x/day and anytime they feel feverish or have 
chills)
MUGA/ECHO (8.3.9)
x
x**
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STUDY 017007: PRETREATMENT, TREATMENT, AND POST-TREATMENT ASSESSMENTS
Screening
Pre-
treatment 
Period
Treatment Period
Post-treatment
(Follow-Up, Disease Progression, EOS)
Note: efficacy evaluations (CT, PET) not 
required after PD or subsequent anticancer 
treatment
Study Day
Approxi-
mately 
1-2 Weeks 
Prior to 
Leuka-
pheresis
Within 
7 days Prior 
to Lympho-
depletion
Lympho-
depletion
Ending 
Day -7 to 
2f
1f
4
8
11
15
22
29
60
90
180
270
365
545
PD
730 
(EOS)
Month
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
2
3
6
9
12
18
N/A
24
Visit Window (days)
± 1
± 1
± 1
± 2
± 2
± 2
± 14
± 14
± 14
± 14
± 14
± 14
N/A
± 14
12-lead ECG(8.3.10)
x
x
HRQoL questionnaires (8.3.13.1)
x
x
x
x
x
x
x
x
x
x
x
Serum pregnancy test (8.3.7)
x
xa
x
x
x
x
Lymphodepleting chemo (8.2.5)
xg
JCAR017 administration (8.2.5.3)
xu
Tumor biopsy (8.3.5)
xk
x
CT (8.3.1)
xc
xl
xm
xm
xm
xm
xm
xm
PET (8.3.1)
x
xc
x l
xm,n
xm,n
xm,n
xm,n
xm,n
x
xm,n
MRI of brain (8.3.1)
xe
xd
xd
xd
xd
xd
xd
xd
CBC w/differential (8.3.7)
x
x
x
x
x
x
x
x
x
xb
xb
xb
xb
xb
xb
x
Coagulation (8.3.7)
x
x
x
x
x
x
x
x
x
Chemistries (8.3.7)
x
x
x
x
x
x
x
x
x
x
x
Inflammatory markers (8.3.7)
x
x
x
x
x
x
xd
xd
Serum immunoglobulins (8.3.7)
x
x
xs
xs
xs
xs
xs
xs
xs
Approved
930204685
6.0
v
Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
93
Protocol 017007 Amendment 2.0: 17 Mar 2020
STUDY 017007: PRETREATMENT, TREATMENT, AND POST-TREATMENT ASSESSMENTS
Screening
Pre-
treatment 
Period
Treatment Period
Post-treatment
(Follow-Up, Disease Progression, EOS)
Note: efficacy evaluations (CT, PET) not 
required after PD or subsequent anticancer 
treatment
Study Day
Approxi-
mately 
1-2 Weeks 
Prior to 
Leuka-
pheresis
Within 
7 days Prior 
to Lympho-
depletion
Lympho-
depletion
Ending 
Day -7 to 
2f
1f
4
8
11
15
22
29
60
90
180
270
365
545
PD
730 
(EOS)
Month
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
2
3
6
9
12
18
N/A
24
Visit Window (days)
± 1
± 1
± 1
± 2
± 2
± 2
± 14
± 14
± 14
± 14
± 14
± 14
N/A
± 14
AEs/SAEs (9)
AEs/SAEs related to protocol-
mandated procedure
Collect all AEs from lymphodepleting chemo to 90 days post-last 
dose of JCAR017p
AEs/SAEs related to JCAR017 
and/or protocol-mandated 
proceduresq,r, as well as selected 
AEs listed in section 9
Concomitant medications (6.5)
Con meds 
associated 
with 
AEs/SAEs 
related to 
protocol-
mandated 
procedures
Collect all concomitant meds from lymphodepleting chemo to 90 
days after the last dose of JCAR017
Concomitant meds ongoing at the 
time of AEs/SAEs related to 
JCAR017 and/or protocol-mandated 
procedures, corticosteroids, GVHD 
meds, and anticancer therapies
Anticancer therapies
Throughout study
Hospitalizations (8.3.14)
From first day of lymphodepleting chemotherapy to end of study
AE = adverse event; BMA = bone marrow aspirate; BMB = bone marrow biopsy; CBC = complete blood count; CSF = cerebrospinal fluid; CT = computed tomography; EOS = end of 
study; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; GVHD = graft-versus-host disease; HRQoL = health-related quality of 
life; I/E = inclusion/exclusion; MMSE = Mini-Mental State Exam; MRI = magnetic resonance imaging; MUGA = multiple uptake gated acquisition scan; PD = progressive disease; 
PET = positron emission tomography; PK = pharmacokinetic; qPCR = quantitative polymerase chain reaction; RCL = replication-competent lentivirus; SAE = serious adverse event.
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
94
Protocol 017007 Amendment 2.0: 17 Mar 2020
Schedule of Evaluations Footnotes:
a) Serum pregnancy test must be done within 48 hours prior to lymphodepleting 
chemotherapy. 
b) Not done for subjects who have received subsequent anticancer therapy.
c) Not required if done at the study site for screening and no intervening antitumor 
therapy has been administered. If required, recommended within 14 days prior to the 
start of lymphodepleting chemotherapy and must be done within 6 weeks prior to the 
start of lymphodepleting chemotherapy. For subjects that receive anticancer 
treatment for disease control while JCAR017 is being produced, these assessments 
must be performed after completion of the intervening anticancer treatment and as 
close as possible to the start of lymphodepleting chemotherapy (recommended within 
7-14 days prior to start).
d) If clinically indicated.
e) Required only for subjects with suspected or confirmed CNS involvement, or as 
clinically indicated.
f) All evaluations and laboratory assessments must be done prior to administration of 
lymphodepleting chemotherapy or JCAR017.
g) To be done on each day of lymphodepleting chemotherapy. Prior to first dose, it 
must be confirmed that the subject meets criteria for lymphodepleting chemotherapy
as described in Section 8.2.5.2.
h) Weight only.
i) Measured within approximately 5 minutes before and 15 minutes after infusion, then 
approximately every 15 minutes thereafter for the first hour and hourly (±15 
minutes) for the next 2 hours. Continue to monitor vital signs after this point until 
stable and as clinically indicated.
j) Routine neurological examination only.
k)For subjects with tDLBCL, a pathology report from the biopsy of their current 
relapsed disease is required.
l) PET and CT scan may be performed Day 22 to Day 29.
m) If CR is achieved, only CT scans will be required. Upon progression/relapse or 
initiation of another anticancer treatment, PET and CT scans are no longer required. 
Subjects who receive HSCT post-JCAR017 but no other anticancer treatment should 
continue to undergo PET and/or CT scans in accordance with the previous 
2 sentences. PET scans should be performed to verify PD.
** MUGA/ECHO must be repeated after any intervening cardiotoxic anticancer 
therapy.
n) Not required if CR previously documented. 
o) If more than 1% of cells in test samples collected at the Day 365 visit or later test 
positive for vector sequences, the pattern of vector integration sites will be 
analyzed. If a predominant integration site is detected, then the subject will be asked 
to provide another blood sample 3 months later for follow-up testing.
p) If a subject receives lymphodepleting therapy but not JCAR017, all AEs/SAEs 
should be recorded/reported for 30 days following the last dose of lymphodepleting 
chemotherapy. For subjects starting a subsequent nonchemotherapy-containing 
anticancer therapy (eg, checkpoint inhibitors, IMIDs) prior to 90 days following 
final JCAR017 administration, all AE/SAEs will be collected after initiation of the 
subsequent therapy for 90 days following final JCAR017 infusion or 30 days 
following subsequent therapy, whichever is longer. For subjects starting a 
subsequent chemotherapy-containing anticancer therapy prior to 90 days following 
final JCAR017 administration, only AEs and SAEs related to JCAR017 and/or 
protocol-mandated procedures must be recorded/reported after initiation of 
subsequent therapy.
q) Starting from 91 days after the last dose of JCAR017 until EOS visit.
r) If any of the following clinical conditions are observed, an SAE should be reported 
unless the event can be definitely attributed to an alternative cause: new/secondary 
malignancies; new onset or exacerbation of a pre-existing neurologic disorder; new 
onset of a rheumatologic or other autoimmune disorder; new onset of a hematologic 
disorder; rare and unexpected disorders with an unknown etiology (eg, Guillain-
Barré, Stevens-Johnson syndrome).
s) Not required if B-cell recovery documented without recent administration of 
intravenous immune globulin.
t) Samples may be archived if all samples collected within the first year after the last 
dose of JCAR017 were tested and were negative for RCL.
u) Prior to dose, it must be confirmed that the subject meets criteria for JCAR017
treatment as described in Section 8.2.5.3.
v) Not required if the subject is medically incapacitated and/or medically unable to 
complete.
w) Pregnancy test and contraceptive counseling for women of childbearing potential. 
x) Immunogenicity Assessment; samples will be processed to plasma and analyzed 
for the presence of antibodies that bind to the extracellular region of JCAR017.
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
95
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
96
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
97
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
98
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
99
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
100
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
102
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
107
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

EDMS Doc. Number: 24546003 - 22856872
JCAR017 
Juno Therapeutics,
Protocol 017007 
A Celgene Company
Confidential and Proprietary
108
Protocol 017007 Amendment 2.0: 17 Mar 2020
Approved
930204685
6.0
v
Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 24546003 - 23892300
JCAR017 
Juno Therapeutics,
Summary of Changes 017007 
A Celgene Company
Confidential and Proprietary
3
017007 Amendment 2.0: 17 Mar 2020
1.
JUSTIFICATION FOR AMENDMENT
Significant changes included in this amendment are summarized below:
Study Population

Revised exclusion criteria regarding tumor invasion of vessels and deep venous
thrombosis (DVT)/pulmonary embolism (PE)
 Thus, the exclusion criteria have been revised to only 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.
Revised Sections: Protocol Synopsis, Section 5.2 Exclusion Criteria, Section 8.2.5.3 Criteria 
for JCAR017 Treatment
The amendment also includes several other minor updates, clarifications and corrections:

Protocol title page updated study acronym from TRANSCEND-OUTREACH to
TRANSCEND-OUTREACH-007

Protocol title page updated to include Study ID, NCT number, and 017007 Medical
Monitor mailbox email

Added more detail regarding safety analyses, including more detail on adverse events of
special interest (AESIs) to be analyzed (Protocol Synopsis, Section 2.4, Section 9.1.3)

Estimated total time for all subjects to complete the study from 4 years to approximately
5 years (Protocol Synopsis, Section 4.2)

Clarified exclusion criteria of active hepatitis B and hepatitis C (Protocol Synopsis,
Section 5.2)

Updated contraception requirements, lactation, and pregnancy language (previously
described in Section 5.3) and in Inclusion Criteria to align with program-wide changes.
Pregnancy tests and contraceptive counseling for females of childbearing potential were
also added at study visits every 3 months until 12 months after lymphodepleting
chemotherapy (LDC) (Protocol Synopsis, Section 5.1, Section 9.3.6, Appendix A)
Approved
930204685
5.0
v
Approved
1.0
v

Approved
1.0
v

EDMS Doc. Number: 24546003 - 23892300
JCAR017 
Juno Therapeutics,
Summary of Changes 017007 
A Celgene Company
Confidential and Proprietary
5
017007 Amendment 2.0: 17 Mar 2020

Clarified that creatinine clearance is required only on the first date of LDC (Section
8.2.5.2)

Updated safety reporting requirements to align with program-wide updates (Section 9)

Added new language regarding Future Use of Stored Specimens and Data (Section 12.12)

References were updated (Section 14)

Added quality of life questionnaire requirement at disease progression timepoint
(Appendix A Schedules of Evaluations)

Added tumor biopsy requirement at screening if the patient has transformed diffuse Large
B-cell lymphoma (tDLBCL) and at disease progression (Appendix A Schedules of
Evaluations)

Updated sponsor name from Juno Therapeutics, Inc. to “the Sponsor” throughout the text

Corrected misspellings, style, and formatting
Approved
930204685
5.0
v
Approved
1.0
v