SJCAR19: A Phase I/II Study Evaluating SJCAR19 (CD19-Specific CAR Engineered Autologous T-Cells) in Pediatric and Young Adult Patients ≤ 21 Years of Age With Relapsed or Refractory CD19+ Acute Lymphoblastic Leukemia
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia, in Relapse, Acute Lymphoblastic Leukemia, Refractory
Sponsor: St. Jude Children's Research Hospital

Official Study Title: A Phase I/II Study Evaluating SJCAR19 (CD19-Specific CAR 
Engineered Autologous T-Cells) in Pediatric and Young Adult Patients ≤ 21 Years of Age 
With Relapsed or Refractory CD19+ Acute Lymphoblastic Leukemia  
 
CTG Number: NCT03573700 
 
Document Date: 10/25/2022 
 

Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
St. Jude Children’s Research Hospital
SJCAR19
Initial version dated:  04/26/17 (IRB Approved: 06/30/17) Superseded
Amendment 1.0 dated: 09/26/17 (IRB Approved:12/11/17) Superseded
Amendment 2.0 dated: 05/21/18 (IRB Approved: 06/15/18) Activated: 06/26/18 
Revision 2.1 dated: 10/01/18 (IRB Approved: 10/18/18) Activated : 10/24/2018 
Revision 2.2 dated: 01/18/19 (IRB Approved: 02/05/2019) Activated : 02/15/2019 
Amendment 3.0 dated: 05/07/19 (IRB Approved: 8/9/2019) Activated: 8/26/2019 
Revision 3.1 dated: 09/09/2019 (IRB Approved: 10/28/2019) Activated: 11/25/2019 
Amendment 4.0 dated: 02/20/2020 (IRB Approved: 03/24/2020) Activated: 05/19/2020 
Amendment 5.0 dated: 09/17/2020 (IRB Approved: 12/21/2020) Activated: 02/12/2021 
Revision 5.1 dated: 03/30/2021 (IRB Approved: 04/09/2021) Activated: 04/26/2021 
Revision 5.2 dated: 07/19/2021 (IRB Approved: 08/23/2021) Activated: 09/02/2021 
Amendment 6.0 dated: 06/16/2022 (IRB Approved: 08/22/2022) Activated: 09/30/2022 
Revision 6.1 dated 10/17/2022 (IRB Approved:10/25/2022)  Activated: 11/10/2022
SJCAR19: A PHASE I/II STUDY EVALUATING SJCAR19 (CD19-SPECIFIC CAR 
ENGINEERED AUTOLOGOUS T-CELLS) IN PEDIATRIC AND YOUNG ADULT 
PATIENTS ≤ 21 YEARS OF AGE WITH RELAPSED OR REFRACTORY CD19+ ACUTE 
LYMPHOBLASTIC LEUKEMIA
IND # 18164
Principal Investigators
Aimee C Talleur, MD1
Stephen Gottschalk, MD1
Co-Investigators
Brandon M. Triplett, MD1
Terrence Geiger, MD PhD3
Ewelina Mamcarz, MD1
Hiroto Inaba, MD, PhD6
Ashok Srinivasan, MD1
Esther Obeng, MD, PhD6
Renee Madden, MD1
Benjamin Youngblood, PhD4
Amr Qudeimat, MD1
Paul Thomas, PhD4
Paulina Velasquez, MD1
Charles Mullighan, MBBS, MD3
Salem Akel, PhD1 
Allison Bragg, PharmD5
Akshay Sharma, MD1
Justin Baker, MD6
Cheng Cheng, PhD 2
Deena Levine, MD6
Swait Naik, MBBS1
Liza Johnson, MD6
Caitlin Zebley, MD1
Jiyang Yu, PhD7
Ali Suliman, MD1
Senthil Bhoopalan, MBBS, PhD1
Rebecca Epperly, MD1
Department of Bone Marrow Transplantation and Cellular Therapy1
Department of Biostatistics2
Department of Pathology3
Department of Immunology4
Department of Pharmaceutical Services5
Department of Oncology6
Department of Computational Biology7
St. Jude Children’s Research Hospital
262 Danny Thomas Place
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
Memphis, TN  38105
(901) 595-3300
This is a confidential research document.  No information may be extracted without permission of the principal investigator.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
TABLE OF CONTENTS
OBJECTIVES……………..…………………………………………………………………...1
1.1
Primary Objectives………………………………………………………………………
1
1.2
Exploratory Objectives………………………………………………………………….
1
BACKGROUND AND RATIONALE……………..………………………………………….2
2.1
Overview………………………………………………………………………………...
2
2.2
Relapsed and Refractory Acute Lymphoblastic Leukemia……………………………...
2
2.3
Chimeric Antigen Receptors…………………………………………………………….
2
2.4
Rationale for CD19-specific CAR T-cell Therapy……………………………………...
3
2.5
Rationale for Lymphodepleting Preparative Regimen…………………………………..
4
2.6
Safety Issues with CD19-specific CAR T-cell Therapy ………………………………..
4
2.7
Rationale for Present Study……………………………………………………………...
7
RESEARCH PARTICIPANT ELIGIBILITY CRITERIA AND STUDY 
ENROLLMENT……………………………………………………………………................14
3.1
Eligibility Criteria for Autologous Apheresis…………………………………………...
15
3.2
Eligibility Criteria for SJCAR19 Manufacturing………………………………………..
16
3.3
Eligibility Criteria for Treatment with SJCAR19……………………………………….
16
3.4
Research Participant Recruitment and Screening……………………………………….
18
3.5
Enrollment on Study at St. Jude…………………………………………………………
19
TREATMENT PLAN………………………………………………………………………...19
4.1
Overview of Treatment Process ………………………..…………..…………………...
19
4.2
Cell Procurement, Processing and Infusion……………………………………………..
20
4.3
Bridging Chemotherapy…………………………………..…………..…………………
22
4.4
SJCAR19 Therapy………………………………………..…………..…………………
22
4.5
Supportive Care…………………………….…………..…………..……………………
26
4.6
Concomitant therapy and/or enrollment onto therapeutic protocols post-infusion of 
SJCAR19 ……………………………………………………..…………..……………..
27
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DRUG/DEVICE/BIOLOGIC AGENT INFORMATION………….…………..…………….27
5.1
Medications.…………………….……………………..………………..………………
27
5.2
CliniMACS System …………..…..………………….………………………………...
29
REQUIRED EVALUATIONS, TESTS, AND OBSERVATIONS………………………….30
6.1
Treatment Evaluations…………………………..… ……………………………..……
30
6.2
Patient Reported Outcomes and Quality of Life Evaluations. …………………………
34
6.3
Long-Term Follow-up Evaluations …………………………………………………….
36
EVALUATION CRITERIA………...………………………………………………………..36
7.1
Toxicity Evaluation Criteria……………………………………………..……………...
36
7.2
Disease Response Criteria………………………………….…….…….……………….
37
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF-STUDY 
CRITERIA……………………………………………………………………………………38
8.1
Off Study Criteria……………………………………………………………………….
38
8.2
Off Therapy Criteria…………………………………………………………………….
38
SAFETY AND ADVERSE EVENT REPORTING REQUIREMENTS…………………….39
9.1
Reporting Adverse Experiences and Deaths to St. Jude IRB…………………………...
39
9.2
Reporting to St. Jude Institutional Biosafety Committee ………………………………
40
9.3
Reporting to FDA……………………………………………………………………….
41
9.4
Reporting to St. Jude Office of Regulatory Affairs …………………………………….
41
9.5
Continuing Review Reports……………………………………………………………..
41
9.6
Reporting to the CIBMTR………………………………………………………………
42
  
DATA COLLECTION, STUDY MONITORING, AND CONFIDENTIALITY……………42
10.1
Data collection and submission……………………………………….……..………...
42
10.2
Study Monitoring…………………………..……………………………….…………...
42
10.3
Confidentiality………………………………………………………….……………….
43
10.4
Genomic Data Sharing………………………………………………………………….
43
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IRB NUMBER: Pro00007661
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
STATISTICAL CONSIDERATIONS……………..……………..……….………………….44
11.1
Overview of Statistical Design and Analysis ….……………………..………...............
44
11.2
Dose Limiting Toxicity …………………..……………………………………………..
45
11.3
Dose Escalation ………………………………………………………………...............
47
11.4
Efficacy and Stopping Rules……………………………………………………………
48
11.5
Analysis for Exploratory Objectives……………………………………………………
49
OBTAINING INFORMED CONSENT……………………………………………………53
12.1
Informed Consent……………………………………………………………………….
53
12.2
Informed Consent Prior to Research Interventions……………………………………..
54
12.3
Consent at Age of Majority……………………………………………………………..
54
12.4
Consent When English is Not the Primary Language…………………………………..
54
References……………………………………………………………………………….
55
Appendix A: Karnofsky and Lansky Performance Status …………………….…………
64
Appendix B: Steroid Equivalent Dose Reference Chart……………….………………...
65
Appendix C: Study Overview…..……………………………………….……………….
66
Appendix D: Overview of SJCAR19 Manufacturing Procedure ………..………………
67
Appendix E: Treatment Evaluations Study Calendar ………………….………………..
68
Appendix F: Criteria for Adverse Event (AE) Evaluation and Reporting ………………
Appendix G: Criteria for Cytokine Release Syndrome (CRS) Adverse Event (AE) Grading 
69
70
Appendix H: Criteria for Neurotoxicity Adverse Event (AE) Grading ……………......…
71
Appendix I: Quality of Life Evaluations Study Calendar …….…………………….…..
73
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IRB NUMBER: Pro00007661
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
STUDY SUMMARY
Protocol Title
SJCAR19: A Phase I/II study evaluating SJCAR19 (CD19-specific CAR engineered autologous T-
cells) in pediatric and young adult patients ≤ 21 years of age with relapsed or refractory CD19+ acute 
lymphoblastic leukemia
Principal Investigators:
Aimee C Talleur, MD
Stephen Gottschalk, MD
Brief Overview
Study Population:
Patients less than or equal to 21 years old with relapsed or refractory CD19+ acute lymphoblastic 
leukemia, as defined by protocol eligibility criteria. Additional eligibility criteria are specified to 
assure sufficient multi-organ system function.
Intervention, Brief Outline, and Objectives of Treatment Plan:
Modern frontline therapy for patients with CD19+ acute lymphoblastic leukemia (ALL) is based on 
intensive administration of multiple drugs.  In patients with relapsed or refractory disease response 
to chemotherapy is generally poor, and dosages cannot be further increased without unacceptable 
toxicities. For most patients, particularly those who relapse while still receiving frontline therapy, the 
only therapeutic option is hematopoietic cell transplantation (HCT). However, HCT is an intensive 
therapeutic modality with a significant risk of morbidity and mortality, and has limited efficacy in 
patients unable to achieve remission prior to HCT.  Improvement in cure rates requires the 
development of treatments that bypass cellular mechanisms of drug resistance and have high 
therapeutic indexes. One such treatment is chimeric antigen receptor (CAR) engineered T-cells, a 
form of adoptive immunotherapy that has shown immense promise for treating relapsed or refractory 
CD19+ ALL. 
SJCAR19 is a Phase I/II clinical trial evaluating the use of SJCAR19 (CD19-specific CAR 
engineered autologous T-cells) in patients ≤ 21 years old with relapsed/refractory CD19+ ALL. The 
study will contain a three part eligibility criteria: one for autologous apheresis, a second to proceed 
with manufacturing of the SJCAR19 product and a third to proceed with SJCAR19 therapy. A single 
patient cohort will be evaluated, without modifications to therapy based on either disease burden or 
prior allogeneic HCT status. Treatment will include a single treatment course, with most patients 
receiving a lymphodepleting chemotherapy preparative regimen of fludarabine/cyclophosphamide, 
followed by a single infusion of SJCAR19 (with dosing based on the number of CAR+ T cells and 
patient weight). The evaluation period for the primary objectives of both the Phase I and II portions 
of the study will be 4 weeks. Long-term follow-up will occur for 15 years as per FDA guidance. 
Follow-up will occur on protocol for the 1 year after the last SJCAR19 infusion. After one year, 
patients will be approached and consented to our existing long-term follow-up (LTFU) institutional 
protocol. If a patient does not enroll on this LTFU protocol, we will continue to monitor patients on-
study yearly, for up to 15 years post-infusion, per FDA guidance.
The Phase I portion will evaluate the safety and maximum tolerated dose (MTD) of SJCAR19, 
using a standard 3+3 study design and a 4 week post infusion of SJCAR19 evaluation period. 
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
The Phase II portion will evaluate the efficacy, and provide further safety evaluation, of 
SJCAR19 in an expansion cohort at the MTD determined in the Phase I portion of the study. 
Patients treated at the MTD in the Phase I portion of the study will be evaluated for efficacy in 
the Phase II portion. Patients enrolled on the Phase II study and who meet protocol defined 
criteria, may receive subsequent therapy with lymphodepleting chemotherapy and reinfusion of 
the SJCAR19 product. 
IND/IDE: IND #18164
Criteria for Evaluation – Safety and Efficacy
Safety: Ongoing assessment of toxicity will be done using the NCI CTCAE version 5.0. 
Cytokine release syndrome and neurotoxicity will be graded and assessed based on ASTCT 
consensus grading system similar to that used in established CAR+ T-cell clinical trials 
(appendix G and H). The evaluation period for dose-limiting toxicities will be 4 weeks post-
infusion of SJCAR19. 
Efficacy: The primary measure of efficacy will be the complete response rate at 4 weeks post-
infusion of SJCAR19.
Statistical Considerations and Data Analysis
Study Design: Phase I/II
Randomization: No
Sample Size:  Total: up to 24 evaluable patients; Phase I: 9-12 patients, Phase II: 12 patients
Data Analyses:
Anticipated primary completion date: July 1, 2023
Anticipated study completion date: July 1, 2024
Time frame for primary outcome measure:  4 weeks post-SJCAR19 infusion
Data Management including statistical evaluations
Protocol compliance, data collection including safety data, and reporting will be carried out by 
the Department of Bone Marrow Transplantation and Cellular Therapy Research Office.
Statistical considerations and ongoing analysis will be conducted by Dr. Cheng Cheng and 
designated associates within the St. Jude Department of Biostatistics.
Human Subjects:
The risks to participants are primarily related to autologous apheresis, the conditioning regimen, 
the cellular infusion and in vivo toxicity of SJCAR19. CD19-specific CAR T-cell therapy has 
been associated with cytokine release syndrome, neurotoxicity and B-cell aplasia.  Adverse 
events will be treated, monitored, and reported appropriately. Possible benefits of participation 
include obtaining and/or sustaining disease remission. In addition, there is the possibility of 
psychological benefit from knowing participation has helped researchers gain more 
understanding about SJCAR19. Potential alternatives to participation include chemotherapy, 
HCT, other research treatment if available, and/or supportive therapy alone. The possible 
benefits, alternatives to participation, and side effects, including that there may be unknown side 
effects of treatment, are detailed in lay language within the respective informed consent 
document. 
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

SJCAR19 - 1
Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
1.0 OBJECTIVES
1.1 Primary Objective
1.1.1 The primary objectives for the Phase I study portion are to determine the 
maximum tolerated dose (MTD) and characterize the safety profile and dose-
limiting toxicities (DLTs) of treatment with SJCAR19 in pediatric and young 
adult patients ≤ 21 years of age, with relapsed or refractory CD19+ ALL. 
1.1.2 The primary objective for the Phase II study portion is to evaluate the complete 
response (CR) rates of SJCAR19 in pediatric and young adult patients ≤ 21 years 
of age, with relapsed or refractory CD19+ ALL.
1.2 Exploratory Objectives
1.2.1 To describe the feasibility of manufacturing SJCAR19 for pediatric and young 
adult patients ≤ 21 years of age, with relapsed or refractory CD19+ ALL, and 
explore possible factors contributing to manufacturing failure. 
1.2.2 To evaluate the relapse-free survival of patients with minimal residual disease at 
the time of treatment with SJCAR19.
1.2.3 To study the expansion, persistence and phenotype of SJCAR19.
1.2.4 To characterize the cytokine profile in the peripheral blood and CSF after 
treatment with SJCAR19.
1.2.5 To explore the use of next-generation sequencing (NGS) for the monitoring of 
disease status post-treatment with SJCAR19 compared to minimal residual 
disease detection via flow cytometry.
1.2.6 To assess whether SJCAR19 cells acquire functional versus exhaustion-associated 
epigenetic programs during in vitro and in vivo expansion.
1.2.7 To determine immune reconstitution post SJCAR19 treatment, and the clonal 
structure and endogenous repertoire of SJCAR19 cells during in vitro and in vivo 
expansion.
1.2.8 To longitudinally assess and quantify the symptoms, associated distress, and 
functional impairment experienced by patients enrolled on this Phase I/II clinical 
trial.
1.2.9 To longitudinally assess and quantify numerous metrics of quality of life and 
well-being for patients enrolled on this Phase I/II trial and their primary 
caretakers.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

SJCAR19 - 2
Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
1.2.10To characterize incidence and mechanisms of resistance and/or relapse post-
therapy with SJCAR19.
2.0 BACKGROUND AND RATIONALE
2.1 Overview
SJCAR19 is a Phase I/II clinical trial evaluating the use of SJCAR19 (CD19-specific 
CAR engineered autologous T-cells) in pediatric and young adult patients ≤ 21 years 
old, with relapsed/refractory CD19+ acute lymphoblastic leukemia. This study will 
evaluate the safety and maximum tolerated dose (Phase I), and efficacy (Phase II) of 
SJCAR19. The study will contain a three part eligibility criteria: one for autologous 
apheresis, a second to proceed with manufacturing of the SJCAR19 product and a 
third to proceed with SJCAR19 therapy. Treatment will include a single treatment 
course, with most patients receiving a lymphodepleting chemotherapy preparative 
regimen of fludarabine/cyclophosphamide, followed by a single infusion of SJCAR19 
(with dosing based on the number of CAR+ T cells and patient weight). Patients 
enrolled on the Phase II study and who meet protocol defined criteria, may receive 
subsequent therapy with lymphodepleting chemotherapy and reinfusion of the 
SJCAR19 product. Primary objectives will be evaluated at 4 weeks post-infusion with 
SJCAR19. Long-term follow-up will occur for 15 years as per FDA guidance. 
Follow-up will occur on protocol for the 1 year after the last SJCAR19 infusion. After 
one year, patients will be approached and consented to our existing long-term follow-
up (LTFU) institutional protocol. If a patient does not enroll on this  LTFU protocol, 
we will continue to monitor patients on-study yearly, for up to 15 years post-infusion, 
per FDA guidance.
2.2 Relapsed and Refractory Acute Lymphoblastic Leukemia 
Acute lymphoblastic leukemia (ALL) accounts for approximately 25% of new 
pediatric cancer cases diagnosed each year in the United States. Although cure rates 
for pediatric ALL have steadily improved and are now nearing 90%, patients with 
relapsed or refractory disease do much poorer.2, 3  Treatment options are typically 
limited for these patients, and therapy relies primarily on hematopoietic cell 
transplantation (HCT).4-7 Second remissions are achieved in the majority of relapsed 
ALL patients but overall cure rates seldom exceed 30%, with leukemic relapse after 
HCT remaining the most common cause of failure.8-12 Relapse after HCT can be even 
more difficult to treat due to the development of increased resistance to 
chemotherapy, resistance to donor lymphocyte infusions, and often multiple 
comorbid conditions secondary to disease or prior treatments, all of which can limit 
therapeutic choices.13 Significant improvement in cure rates requires the development 
of treatments that bypass cellular mechanisms of drug resistance and have high 
therapeutic indexes. 
2.3 Chimeric Antigen Receptors 
Chimeric antigen receptors (CARs) have been developed as a form of adoptive 
immunotherapy. CARs typically combine the single chain variable fragment (scFv) of 
an antibody or the extracellular domain of a receptor, with a transmembrane domain 
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SJCAR19 - 3
Amendment 6.1, dated 10/17/2022
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and the intracellular signaling domains of the CD3ζ chain and costimulatory 
molecules. A CAR can be constitutively expressed on the surface of a T-cell through 
non-viral or viral transduction, thereby enabling a cytotoxic T-cell to recognize 
certain targets in an antigen-specific manner.14-17 CARs can be designed to target a 
specific tumor-associated antigen and thereby can be used for anticancer therapy.18-20  
Different generations of CARs have been developed in attempts to improve 
persistence and expansion and efficacy, including the addition of costimulatory 
receptors such as CD28 and 4-1BB.16, 17, 21-25 
2.4 Rationale for CD19-specific Chimeric Antigen Receptor Therapy
Leukemia cells can be delineated by the surface markers they express, and these 
markers are potential targets for immunotherapy. CD19 is one such surface marker. 
CD19 is a 95kDa glycoprotein. It is found on the surface of B cells from early on in 
development until they differentiate into plasma cells, but is not found on 
hematopoietic progenitor cells.26-29 CD19 is an attractive target for CAR therapy 
because its expression is restricted in normal host tissues to B lineage cells, but is also 
expressed by most B cell ALL cells.25, 28 
Several pediatric institutions and pharmaceutical companies are currently 
investigating the use of autologous CD19-specific CAR T-cell therapy in a 
relapsed/refractory CD19+ ALL disease patient cohort, and have seen great success to 
date.16, 19, 21, 30-32 Major differences between these ongoing trials include vector 
construct and costimulatory endodomain (CD28 vs 4-1BB), lymphodepleting 
chemotherapy regimens prior to the CAR T-cell infusion, CAR T-cell 
doses/schedules and disease specific inclusion criteria. Despite these differences, the 
efficacy and toxicities, as outlined below, have been similar across various 
institutions. 
Seattle Children’s Hospital: Investigators are evaluating a lentiviral vector that 
encodes a CD19-specific CAR with a 4-1BB.ζ endodomain and truncated EGFR 
separated by a 2A sequence. The use of pre-lymphodepleting chemotherapy is 
optional and initial cohorts are determined based on prior allogeneic transplant status. 
Infusion doses are based on the number of CAR+ T cells and the product is composed 
of defined CD4:CD8 T-cell subsets. Preliminary results from their Phase I trial 
including 13 patients, shows a molecular remission rate of 85%.33 
National Institute of Cancer: Investigators have evaluated a retroviral vector that 
encodes a CD19-specific CAR with a CD28.ζ endodomain. Treatment cohorts are 
determined by level of disease burden. The lymphodepleting chemotherapy regimen 
varies based on cohort, and dosing levels use the number of CAR+ T cells. Intent to 
treat analysis of 21 patients demonstrated a complete response rate of 67%.33, 34 This 
CD19-specific CAR T-cell product (KTE-C19) is now being evaluated by KITE 
Pharma in a Phase II multicenter trial. All patients receive a lymphodepleting 
chemotherapy regimen of fludarabine and cyclophosphamide, and KTE-C19 dosing is 
determined by the number of CAR+ T cells and patient weight. Initial reports show 
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SJCAR19 - 4
Amendment 6.1, dated 10/17/2022
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that the regimen appears to be safe and feasible, with promising efficacy, but numbers 
are small at this time.35 
Memorial Sloan Kettering: Investigators are evaluating a retroviral vector that 
encodes a CD19-specific CAR with a CD28.ζ endodomain in two cohorts that are 
defined by level of disease burden. The conditioning regimen is uniform for all 
participants and dosing is based on the number of CAR+ T cells. This study does not 
yet have reportable results, but a similar study design in adult patients demonstrated a 
28-day complete response rate of 88%.33 
Children’s Hospital of Philadelphia/University of Pennsylvania: Investigators have 
evaluated a lentiviral vector that encodes a CD19-specific CAR with a 4-1BB.ζ 
endodomain (CTL019), using varied lymphodepleting regimens. Dosing levels are 
determined by the total number of T cells, not CAR+ T cells. The reported 12-month 
overall survival rate for 53 patients is 78%.22, 32 CTL019 was also evaluated in a 
multi-center trial (ELIANA) by Novartis. Analysis of this trial showed a 12-month 
overall survival rate of 76% and event-free survival rate of 50%.36, 37 In 2017, this 
product (Kymriah) received FDA approval for the treatment of patients aged 1 – 25 
years old with refractory or relapsed (2nd or greater) CD19+ ALL. 
2.5 Rationale for Lymphodepleting Preparative Regimen
The lymphodepletion of host T cells prior to the adoptive transfer of CAR T-cells may 
enhance the effectiveness and survival of the CAR T-cells. T cell homeostasis is 
controlled by several factors, including access to antigen-presenting cells (APCs), 
major histocompatibility complex (MHC) presentation of self and foreign peptides and 
antigens, interactions with regulatory T cells, and competition for cytokines.38, 39 The 
elimination of host lymphocytes allows transferred cells increased access to APCs and 
peptides being presented by MHC. It also eliminates regulatory T-cells, and other 
competing elements of the immune system that act as cytokine sinks, allowing for 
increased availability of cytokines to be used by transferred T cells.39-41 
The chemotherapy agents fludarabine and cyclophosphamide are commonly used for 
lymphodepletion.38 This drug combination has been used in several CD19-specific 
CAR T-cell therapy trials.22, 34, 35, 42, 43 Studies have shown that the addition of 
fludarabine to cyclophosphamide improves the persistence and expansion of CAR-
engineered T cells44, in part possibly due to the effects of the chemotherapy agents on 
host cytokines and chemokines.45
2.6 Safety issues with CD19-specific CAR T-cell Therapy 
Potential adverse events from CD19-specific CAR T-cell therapy include those 
related to 1) the apheresis of autologous cells, 2) the risks of the preparative regimen 
agents, 3) the infusion of the cellular product, 4) general consequences of lentiviral 
transduction and 5) in vivo consequences related to therapy with CD19-specific CAR 
T-cells.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

SJCAR19 - 5
Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
2.6.1
Apheresis of Autologous Cells
Autologous apheresis is performed to obtain the peripheral blood 
mononuclear cells needed for manufacturing CAR T-cells. Apheresis is 
performed using either a peripheral or temporary central line. During the 
collection, donors are exposed to drugs to prevent their blood from 
clotting; these drugs may include citrate and/or heparin. Donors are 
monitored closely for side effects from these drugs, including 
hypocalcemia and bleeding. After donation, donors may experience a 
decrease in platelet or red blood cell counts, requiring the need for 
transfusion. Overall, apheresis is generally well tolerated.
2.6.2
Lymphodepleting Chemotherapy
The chemotherapy agents fludarabine and cyclophosphamide are 
commonly used as a lymphodepleting preparative regimen.38 This drug 
combination has been used in several CD19-specific CAR T-cell therapy 
trials.22, 34, 35, 42, 43 Both drugs are commercially available and a list of their 
toxicities are included in Section 5.1. 
2.6.3
Infusion of CAR product
CAR-engineered T cell products contain a percentage of transduced and 
untransduced T cells. All of the cells have undergone ex-vivo activation 
and expansion.  Studies have evaluated the risks of infusion of ex-vivo 
activated autologous T cells, with minimal side effects noted.46, 47 
Additionally, CD19-specific CAR autologous T cell trials have not 
reported significant infusion-related reactions.22, 34, 48
2.6.4
General Risks of Lentiviral Transduction
Efficient and stable expression of CD19-specific CARs in T cells requires 
the use of viral vectors for delivery. The use of viral vectors has a 
potential risk of cell transformation resulting from insertional 
mutagenesis,49 a risk that appears to be dependent on the therapeutic gene 
carried by the vector,50 and/or on the cell population targeted by the 
vector.51 Lentiviruses are a subclass of the retrovirus family. Lentiviral 
vectors are commonly used in CD19-specific CAR T-cell therapy trials.22, 
35, 36 33 Lentiviral vectors are capable of stably integrating into a target 
cell’s genome, including quiescent cells. Several strategies have been 
employed to reduce the risk of insertional mutagenesis, including the use 
of self-inactivating (SIN) vectors, chromosomal insulators and tissue-
specific promotors.51, 52 Additionally, a risk of using lentiviral vectors is 
the generation of a replication competent lentivirus (RCL) during the 
manufacturing process. This risk is minimized by current vector 
manufacturing practices.53 Long term follow-up of human trials using 
lentiviral vectors have thus far not reported oncogenic mutagenesis.54, 55 
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2.6.5
Post-Infusion Risks
Based on other studies of CD19-specific CAR T-cell therapy, common 
toxicities include cytokine release syndrome, neurotoxicity and B-cell 
aplasia.25, 31, 48, 56-58
2.6.5.1 Cytokine Release Syndrome
Cytokine release is induced by activated CAR T-cells after 
engagement with their target. This cytokine release causes varying 
degrees of a systemic inflammatory response, referred to as 
cytokine release syndrome (CRS). CRS typically occurs within the 
first 1-2 weeks after infusion of the CD19-CAR T-cell product, 
correlating with the timing of maximal CAR-T expansion and 
proliferation.56, 59 The most commonly observed manifestations 
have 
included 
fever, 
hypotension, 
vascular 
leak, 
renal 
complications with a rise in creatinine or renal failure, and 
pulmonary complications with hypoxia or pleural effusions. CRS 
can generally be medically managed with supportive care; in 
severe cases, CRS has been treated with monoclonal antibody 
therapy against IL-6 or TNF-alpha, and corticosteroids.56-58, 60-62
2.6.5.2 Neurotoxicity
Neurologic changes after receipt of CD19-CAR T-cells have been 
reported. Similar to CRS, these events often correlate with peak T-
cell expansion and cytokine release, but can also occur 
independently of CRS. The spectrum of observed neurologic 
toxicities is vast, without localization to any one neuroanatomic 
location. Reported toxicities include headache, confusion, 
hallucinations, altered mental status, encephalopathy, ataxia, 
cranial nerve palsy, seizures, apraxia, dysphagia and tremors.57, 58 
No clear patient or treatment factors have been elucidated that can 
predict the development of neurotoxicity, including the presence of 
CNS leukemia.56 Observed neurotoxicities have generally been 
brief and self-limited, resolving over several days and without long 
term deficits.25 Providing prophylactic antiepileptic medication is 
not standard of care, but may be considered on a case by case 
basis.
2.6.5.3 B-cell Aplasia
Because CD19 is universally expressed on B-cells, including early 
B-cell precursors, recipient B-cell aplasia is an expected on-
target/off-tumor effect of CD19-specific CAR T-cell therapy. B-
cell lymphopenia and hypogammaglobinemia are expected while 
CD19-specific CAR T-cells persist in the recipient, and should 
resolve if/when the CD19-specific CAR T-cells were to diminish.33  
2.6.5.4 Risk of developing a “false positive” HIV test
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After taking part in this study, participants may test positive for 
HIV on screening tests. There is a difference between testing 
positive on the screening test and actually having an HIV infection. 
There are no definite tests that can tell the difference between these 
two cases at the moment, but we will notify participants if a test is 
developed in the future.63
2.7
Rationale for Present Study
2.7.1
SJCAR19
Researchers at St. Jude have developed a second generation lentiviral 
CD19-specific CAR construct, containing a 4-1BB.ζ domain. This vector 
is being produced in the St. Jude GMP facility using a stable producer cell 
line.64 Pre-clinical, translational evaluation of this CAR vector has proved 
promising (unpublished data, Figure 1), including in the allogeneic 
effector T-cell setting.65  This is the first clinical study evaluating the 
safety and efficacy of this CAR construct for the treatment of pediatric 
relapsed or refractory CD19+ ALL, with the final CAR-engineered 
autologous 
T-cell 
product 
being 
referred 
to 
as 
SJCAR19. 
2.7.2 Relapsed/Refractory ALL Criteria
Relapsed and refractory ALL is often difficult to treat due to increased 
chemoresistance of the leukemic blasts. Those with high-risk relapse, such 
as CD19+ ALL with early relapse or history of slow response to up-front 
induction therapy, are typically referred for treatment with HCT as their 
chance of long-term cure with conventional therapy alone is dismal.4 For 
those patients that relapse after initial HCT, or those that are unable to 
proceed to HCT for reasons such as disease status, donor availability or 
patient health status, treatment options are limited. Additionally, patients 
with refractory CD19+ ALL are a high-risk, difficult to treat population. 
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As the overall success of HCT for ALL is largely dependent on the ability 
to achieve disease remission prior to HCT, having refractory disease 
significantly decreases the effectiveness of HCT.66 Since these patients are 
chemorefractory, there is a need for therapeutic options that utilize non-
chemotherapy treatment options that serve as a bridge to HCT, or an 
alternative to HCT. 
The relapsed and refractory disease inclusion criteria for SJCAR19 are 
modeled after the disease classification criteria that is currently being used 
by the St. Jude Leukemia Division. They are intended to provide those 
patients with chemorefractory disease, either primary refractory or at time 
of relapse, a novel therapeutic option that may serve as a bridge to HCT or 
as a stand-alone treatment option. This includes those patients that may 
require HCT, but are unable to receive HCT due to ineligibility and/or 
unsuitability.  Additionally, SJCAR19 will provide a treatment option for 
those patients that relapse after HCT or experience multiple relapses, a 
patient population that is historically difficult to treat using conventional 
therapy. 
2.7.3 Early Autologous Apheresis
When manufacturing a CAR T-cell product the quality of the apheresis 
sample, specifically the quantity and/or quality of circulating T cells, can 
affect the ability to generate a final CAR-T product. However, it is not 
known when the “best” time to collect autologous cells is.43, 67  Many 
CAR T-cell trials collect patient cells at a time in their disease process 
where they have already undergone several treatment modalities, and 
institutions have reported inabilities to manufacture adequate products for 
a small subset of patients.33, 68 Therefore, in this study we are using a 3-
part eligibility criteria: one for apheresis, one for manufacturing and one 
for treatment with SJCAR19. The goal of this design is to allow for the 
apheresis of some patients earlier in their disease process, prior to 
receiving months of treatment, in an attempt to maximize the ability to 
generate the SJCAR19 treatment product if/when it is needed. In addition 
to those patients that we anticipate will go on to be evaluated for 
SJCAR19 therapy (those considered to have refractory or relapsed 
disease), we are proposing apheresis of patients with CD19+ ALL who 
have other high-risk features, such MRD ≥ 1% at the end of up-front 
induction therapy or Hypodiploid disease, independent of risk 
classification at that time. With this earlier apheresis, there is a possibility 
that some patients will undergo the apheresis procedure, but not ultimately 
be eligible for treatment with SJCAR19. Looking at data from Total XVI, 
St. Jude’s most recent up-front leukemia trial, there were 6 patients 
classified as either low or standard risk CD19+ ALL (1.2% of all CD19+ 
ALL patients enrolled on study) that would have met our proposed MRD 
criteria for apheresis. All of these patients were eventually upstaged and 
classified as high-risk, and therefore would ultimately have met disease 
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criteria for therapy with SJCAR19. Therefore, we anticipate that the 
number of patients who undergo apheresis and do not end up meeting 
disease eligibility criteria for treatment with SJCAR19 to be minimal. 
2.7.4
Dose Escalation 
The dose escalation schema of SJCAR19 is based on the experiences and 
results of similar CD19-specific CAR T-cell therapy protocols in pediatric 
and young adult patients with relapsed/refractory CD19+ ALL. The Seattle 
Children’s Phase I trial has infused a range of 5 x 105 – 5 x 106 CAR+ T-
cells/kg. A MTD has not yet been reported.33  The Phase I study at the 
National Cancer Institute determined the MTD of their retroviral product 
to be 1 x 106 CAR+ T-cells/kg.33, 34 Memorial Sloan Kettering is infusing 
either 1 x 106 or 3 x 106 CAR+ T-cells/kg, depending on patient disease 
status at time of enrollment. The group at Children’s Hospital of 
Philadelphia has infused a wide range of CAR+ T-cells, ranging from 1 – 
17.36 x 106 CAR+ T-cells/kg.22  The ELIANA trial administered 2 – 5 x 
106 CAR+ T-cells /kg, with a maximum dose of 2 x108 CAR+ T cells for 
those patients weighing ≥ 50kg.36 ZUMA-4 is evaluating 1 – 2 x106 CAR+ 
T-cells/kg, and have not yet reported a patient experiencing a dose limiting 
toxicity.35 Additionally, the recently FDA approved CD19-specific CAR T 
product, Kymriah, provides dosing ranges that are based on the experience 
in these trials. Therefore, from this collective data, we are proposing a 
starting dose of SJCAR19 of 1 x 106 CAR+ T cells/kg, and will include a 
standard maximum dose.  
2.7.5
SJCAR19 Biology: Epigenetics and T-cell Exhaustion 
While CAR T-cells undergo robust expansion upon transfer into patients 
containing antigen-presenting tumor cells, several studies have indicated 
that they subsequently undergo functional exhaustion during their anti-
tumor response.69, 70  This functional impairment often results in 
significant contraction in the total number of circulating CAR T-cells, 
leaving the host without long-lived immunity to the tumor. Several studies 
have demonstrated that CD8 T-cell exhaustion manifests through changes 
in gene regulation that can be reinforced and heritably maintained.71-73 
Transcriptional memory is often mediated by epigenetic modification to 
the genome, therefore we will use exhaustion-specific epigenetic programs 
as biomarkers to delineate between nonfunctional and functional CAR T-
cells during product development and following adoptive transfer. 
The following work is ongoing in the Youngblood laboratory at St. Jude. 
They have recently determined that conditional deletion of the DNA 
methyltransferase 3a (Dnmt3a cKO) inhibits acquisition of de novo DNA 
methylation programs in antigen-specific CD8 T-cells and prevents T-cell 
exhaustion during chronic viral infection. Importantly, Dnmt3a deficient 
antigen-specific CD8 T-cells retain their ability to mount a polyclonal 
effector response, and ultimately control the chronic pathogen. Moreover, 
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Dnmt3a cKO cells remain resistant to T-cell exhaustion even when the 
cKO cells are forced to persist in an environment that has artificially high 
levels of antigen for several months. Published and unpublished data serve 
as proof of principle that acquired epigenetic programs promote T-cell 
exhaustion, and can be used as a biomarker to assess the developmental 
state of the cell. They have recently developed protocols for performing 
whole-genome methylation analysis using low input genomic DNA, and 
have applied this methodology to determine the epigenetic signature of 
functional human memory CD8 T-cells (Figure 2).  From their whole-
genome analysis they have identified differentially methylated regions 
among the memory T cell subsets and have developed a PCR based assay 
to define the developmental status of the T cells.1 These data provide 
insight into the poised state for expression of critical effector molecules 
and inhibitory receptors among the memory CD8 T-cell subsets. 
In this study, we will perform methylation analyses of CAR T-cells pre 
infusion and following adoptive transfer, to measure changes in epigenetic 
programs that are coupled with the stable changes in the developmental 
status of the cells.  Loci-specific analyses can be performed with a few 
hundred cells, and they have currently optimized conditions to perform 
whole-genome bisulfite sequencing on ~20,000 cells. Loci-specific 
analyses may include regions of the genome that code for effector 
Figure 2: Whole-genome bisulfite sequencing of human T-cell subsets identifies demethylated and de novo 
methylated loci. WGBS methylation profiling provides nucleotide resolution methylation profiling maps of rare 
T-cell populations and can be used to identify differentially methylated regions (DMRs) that are coupled to 
function. A representative map of WGBS profiling of healthy naïve and functional memory T-cell subsets 
(Tscm, Tcm, Tem) is shown for the perforin locus. Red and blue lines represent methylation locations. This 
assay has identified DMRs in effector and lymphoid homing loci that correlate with the known cell subset-
specific phenotypic and functional properties. Demethylation and de novo methylation DMRs will be validated 
with loci-specific PCR assays. Representative demethylation and de novo DNA methylation DMRs are shown 
for perforin, interferon gamma, Tcf1, and CCR7 promoters. WGBS and loci-specific data were collected at the 
St Jude Hartwell Sequencing Facility.1
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molecule, inhibitory receptor, and homing molecule loci including, 
granzyme b, perforin, PD-1, CTLA4 Lag3, 2B4, and CD62L. They will 
perform loci-specific analyses with samples that yield <10,000 PD-1+ T-
cells.  Whole genome bisulfite sequencing may be performed on samples 
that yield >10,000 PD-1+ T-cells.
2.7.6 
SJCAR19 Biology: Clonal Structure and Endogenous Repertoire
CAR T-cells each contain an identical antigen receptor that mediates their 
anti-tumor function. However, these transduced receptors do not replace 
the endogenous receptors present in these T-cell populations prior to 
transduction with the CAR construct. Investigators in the Thomas 
laboratory at St. Jude, and others, have demonstrated in mouse and human 
T-cells that the T cell receptor can serve as a unique “barcode” for a clonal 
lineage, as each receptor within an individual is generally found only in a 
single naïve precursor T-cell.74 Thus, by using techniques to sequence the 
T-cell receptor repertoire in a quantitative manner in combination with the 
HLA type of the CAR-T cell recipient, either by single cell RT-PCR 
approaches, or UMI-RT-PCR bulk methods, we can determine whether 
individual clonal lineages preferentially expand in vitro and in vivo.75  
Despite containing an identical receptor, stochastic effects and cross-talk 
from the endogenous receptor may cause differential expansion of 
individual clonal lineages, as has been observed for transgenic T-cells in 
mice.76 Excessive expansion of only a few “founder” clones could 
contribute to accelerated exhaustion. Thus, this analysis will address two 
questions relevant for CAR T-cell therapy: 1) Does uneven expansion of 
founder populations occur in CAR T-cell therapy? If so, 2) are there 
correlations between the specificity of endogenous antigen receptors and 
preferentially expanded clones?
This study will include repertoire analysis (including use of HLA) and 
quantitative assessment of repertoire diversity and specificity will be used 
on longitudinal samples from in vitro and in vivo expanded CAR T-cell 
populations.77 Outcomes will include the diversity (assessing both richness 
and evenness) of CAR T-cell and unmodified immune cell populations 
over time and the identification of receptor families from known 
specificities (e.g. common infections such as influenza, herpesvirus etc) 
that preferentially associate with expanded clones. Functionality of 
immune responses may be explored using standard methods including 
Elispot assays or determining, for example, the viral load by PCR analysis. 
Additionally, lentiviral vector integration site (VIS) analyses will be 
performed to track the clonal structure of genetically-modified CAR T 
cells.
2.7.7 
Patient Reported Symptoms and Quality of Life 
It has previously been shown that clinician-reported adverse event data 
underestimates the number and severity of symptoms patients are 
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experiencing.78 However, patient reported outcomes have been shown to 
be more reliable measures of adverse events in the adult population. 
Patient symptoms can be prospectively assessed using the Patient 
Reported Outcomes version of the Common Terminology for Adverse 
Events (PRO-CTCAE). The PRO-CTCAE has been validated in adults, 
and inclusion of the adult PRO-CTCAE is now expected in any National 
Cancer Institute-funded clinical protocol. There is increasing interest in 
using patient reported outcomes to assess symptoms in pediatric oncology 
patients,79, 80 and the PRO-CTCAE is currently undergoing validation 
studies at multiple pediatric cancer centers, including at St. Jude. We 
expect that the PRO-CTCAE will be fully validated in the pediatric 
population by completion of the SJCAR19 protocol. By including this 
novel tool to prospectively assess patient symptoms over time, we expect 
that SJCAR19 will be one of the first clinical trials to report adverse event 
data in pediatric patients using the PRO-CTCAE.
Patient and caretaker quality of life may be affected by physical 
symptoms, medical treatments, social support, ability to participate in 
activities and social functioning. Evaluation of the quality of life (QoL) of 
research participants and their primary caretakers has been incorporated 
into several clinical trials at St. Jude. As part of this current study, we plan 
to assess patient and primary caretaker quality of life and symptomatology 
using a similar battery of instruments to those used on the previous clinical 
trials SJPDGF and SJHG12. These evaluations consist of questionnaires to 
be filled out by research participants and primary caretakers, as well as 
semi-structured interviews. In this study, we also intend to use semi-
structured interviews to qualitatively probe patient symptomatology in 
hopes of gaining a better understanding of the experience of poorly 
characterized CAR T-cell-specific side effects, including neurologic 
changes.
Little is known about the effect of caretaker activation on measures of 
caretaker quality of life, especially during an intense treatment phase. 
Research has demonstrated that adults with greater activation have better 
healthcare experiences, and that interventions aimed at increasing 
activation are associated with improved health and healthcare quality.81 In 
this study we will assess primary caregiver activation, defined as the 
primary caregivers’ willingness to manage the patient’s health and 
healthcare and is based on the caretaker’s knowledge, skills, and 
confidence in managing the patient’s health. We will also longitudinally 
assess numerous aspects of primary care giver quality of life including 
hope, anxiety and depression, and spiritual well-being. We hope that 
exploring the relationship between QoL and activation to inform further 
research in this developing field of study. 
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When possible, questionnaires will be administered in the participant’s 
native language. All questionnaires are available in English. A subset of 
questionnaires have been validated in Spanish. We will use these validated 
Spanish questionnaires for Spanish-speaking participants. Semi-structured 
interviews will only be conducted in English as the logistics of using 
interpreter services for this purpose are challenging and the validity of 
interpreted 
qualitative 
data 
is 
uncertain. 
Non-English-speaking 
participants will not participate in the qualitative symptom assessment or 
the good day/bad day scale.
2.7.8
Exploration of resistance/relapse mechanisms 
The appearance of leukemia clones resistant or refractory to adoptive 
immunotherapy have been described in clinical trials treating patients with 
ALL with CD19- and CD22-CAR T-cells. Identified resistance 
mechanisms are varied, including antigen downregulation, alternative 
splicing and lineage switch.88-92 To further investigate mechanisms of 
relapse, we plan to perform analysis on leukemic blast samples as well as 
on the tumor microenvironment. This will include flow cytometric 
analysis to investigate antigen downregulation and overexpression of 
inhibitory ligands, analysis of HLA/haplotypes, as well genomic, 
transcriptomic and proteomic analysis of the relapsed leukemia 
populations. 
2.7.9 Reinfusion of CD19-CAR T-cells (Amendment 5.0)
While treatment with CD19-CAR T-cells has shown to induce remission 
in the majority of pediatric ALL patients, duration of efficacy is variable. 
Given the multiply relapsed and/or refractory population that is typically 
treated with CD19-CAR T-cell therapy, treatment options for recurrent 
leukemia after CAR-T are extremely limited. Therefore, a primary goal of 
CAR T-cell therapy is to provide long-term remission.  
One mechanism of relapse is the loss of functional CAR T-cells, possibly 
due to poor T-cell fitness/exhaustion or immune mediated rejection. A 
marker of diminishing CD19-CAR T-cell activity is autologous B-cell 
recovery. The timing of which has been shown to associate with risk of 
relapse, such that patients who experience early recovery (often defined as 
≤ 6 months after infusion) have a higher relapse risk. One strategy to 
decrease relapse risk and maintain longer term efficacy is to monitor 
closely for B-cell recovery and, with evidence of early recovery, provide 
repeated infusions of the CAR T-cell product. While early B-cell recovery 
can be a sign of impending relapse, some patients experience both nearly 
concurrently and if disease remains CD19+, repeat infusion of the initial 
CAR T-cell product may again provide efficacy. Given the concern for 
rejection as a mechanism for loss of CAR T-cells, incorporation of an 
intensified lymphodepleting regimen has often been employed to reduce 
the likelihood of immune rejection of the reinfused CAR-T cells. 
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In our experience with patients treated on the Phase I portion of SJCAR19, 
4/12 patients were evaluable for early recovery of autologous B-cells 
(evaluable defined as a responding patient with serial analysis of B-cells in 
the peripheral blood for ≥ 2 months post-SJCAR19 infusion). In these 4 
patients, 3 had autologous B-cell recovery ≤ 6 months after initial infusion 
and all had subsequent recurrence of detectable CD19-positive disease. 
These 3 patients went on to receive a 2nd infusion of their SJCAR19 
product on individualized single patient investigator plans (SPIPs), and 2/3 
achieved a 2nd CR, with expected, minimal toxicities. 
Therefore, in the Phase II portion of this study, we are including the option 
for reinfusion of the originally manufactured SJCAR19 product, for 
patients with evidence of early B-cell recovery (≤ 6 months after infusion) 
and/or detectable disease (≤ 12 months after infusion). This option will be 
reserved for patients who previously responded to their SJCAR19 
infusion, have recovered from prior toxicities and continue to meet 
treatment eligibility criteria (section 3.3). We will include an intensified 
lymphodepletion regimen, with the option to use the 1st infusion 
lymphodepleting chemotherapy regimen (Table 1) per PI discretion. 
Dosing will not exceed the MTD. 
2.7.10
Summary
SJCAR19 will be the first CAR T-cell clinical protocol at St. Jude 
Children’s Research Hospital. We serve a relapsed/refractory CD19+ ALL 
patient population that is in need of new cancer-directed therapies. We are 
equipped to manufacture the SJCAR19 product in our Good 
Manufacturing Practice (GMP) facility, and have extensive clinical 
experience with high-risk patients and their associated complications. 
Other institutions evaluating CD19-specific CAR T-cell therapy have 
shown tremendous efficacy with tolerable toxicities, in this difficult to 
treat population. However, the field is generally new and there is still a 
tremendous amount of information to be learned, including related to the 
optimal timing of apheresis, processing schemas, management of side 
effects and CAR T-cell biology. At St. Jude, we will be able to further 
explore these questions and use this knowledge to contribute to the field, 
as well as to form the basis for our own developing CAR T-cell therapy 
program.  
3.0 RESEARCH PARTICIPANT ELIGIBILITY CRITERIA AND STUDY 
ENROLLMENT
The study will contain a three part eligibility criteria: one for autologous apheresis (section 
3.1), a second to proceed with manufacturing of the SJCAR19 product (section 3.2) and a 
third to proceed with treatment with SJCAR19 (section 3.3).
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According to institutional and NIH policy, this study will accession patients regardless of 
gender and ethnic background. Institutional experience confirms broad representation in this 
regard. However, pregnant and lactating females are excluded from participation as the short 
and long-term effects of the preparative agents and study infusions, as well as the long-term 
effects of the apheresis procedure on a fetus and a nursing child through breast milk are not 
entirely known at this time.
3.1 Eligibility Criteria for Autologous Apheresis
3.1.1 Inclusion Criteria for Autologous Apheresis
3.1.2.1 Age ≤ 21 years old
3.1.2.2 CD19+ ALL with any of the following*:
•
Minimal Residual Disease (MRD) ≥ 1% at end of up-front induction therapy 
•
Hypodiploid (< 44 chromosomes or < 0.95 DNA index) CD19+ ALL with 
detectable disease at the end of up-front induction therapy 
•
Increase in disease burden any time after the completion of up-front 
induction therapy
•
Primary refractory disease despite at least 2 cycles of an intensive 
chemotherapy regimen designed to induce remission
•
Refractory disease despite salvage therapy
•
1st or greater relapse
*note: if patient met CD19+ ALL disease criteria, subsequent receipt of cancer directed 
therapy that eradicates disease does not preclude them from proceeding with this study  
3.1.2.3 Estimated life expectancy of > 12 weeks
3.1.2.4 Karnofsky or Lansky (age-dependent) performance score ≥ 50 (Appendix A)
3.1.2.5 Patients with a history of prior allogeneic hematopoietic cell transplantation 
[HCT] must be clinically recovered from prior HCT therapy, have no 
evidence of active GVHD and have not received a donor lymphocyte infusion 
(DLI) within the 28 days prior to apheresis
3.1.2.6 For females of child bearing age: 
•
Not lactating with intent to breastfeed
•
Not pregnant with negative serum pregnancy test within 7 days prior to 
enrollment
3.1.2
Exclusion Criteria for Autologous Apheresis
3.1.2.1 Known primary immunodeficiency
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3.1.2.2 History of HIV infection
3.1.2.3 Severe intercurrent bacterial, viral or fungal infection
3.1.2.4 History of hypersensitivity reactions to murine protein-containing products
3.2 Eligibility Criteria for Manufacturing SJCAR19
3.2.1
CD19+ ALL with any of the following*:
•
Primary refractory disease despite at least 2 cycles of an intensive chemotherapy 
regimen designed to induce remission
•
Refractory disease despite salvage therapy
•
2nd or greater relapse
•
Any relapse after allogeneic hematopoietic cell transplantation 
•
1st relapse if patient requires an allogeneic HCT as part of standard of care relapse 
therapy, but is found to be ineligible and/or unsuitable for HCT
*note: if patient met CD19+ ALL disease criteria, subsequent receipt of cancer directed therapy that 
eradicates disease does not preclude them from proceeding with this study    
3.2.2
Age: ≤ 21 years of age
3.2.3
Karnofsky or Lansky (age-dependent) performance score ≥ 50 (Appendix A)
3.2.4
Estimated life expectancy of > 12 weeks
3.2.5
Meets eligibility criteria to undergo autologous apheresis, or have previously 
undergone autologous apheresis
3.3 Eligibility Criteria for Treatment with SJCAR19
3.3.1
Inclusion Criteria for Treatment with SJCAR19
3.3.1.1 CD19+ ALL** with any of the following:

Primary refractory disease despite at least 2 cycles of an intensive 
chemotherapy regimen designed to induce remission

Refractory disease despite salvage therapy

2nd or greater relapse

Any relapse after allogeneic hematopoietic cell transplantation  

1st relapse if patient requires an allogeneic HCT as part of standard of care 
relapse therapy, but is found to be ineligible and/or unsuitable for HCT for 
any of the following reasons:
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o
Patients that do not have an available allogeneic donor (defined as 
at least a 7/8 HLA-matched related/unrelated donor, 5/6 HLA-
matched umbilical cord donor, or 3/6 HLA-matched haploidentical 
donor)
o
Patients with refractory leukemia, for which allogeneic transplant 
is known to be less effective in the B-ALL population, and
o
Patients who are unable to receive myeloablative total body 
irradiation (TBI), which is included in standard transplant 
regimens for patients with B-ALL. 
**ALL must be confirmed to be CD19+ within 3 months prior to enrollment for 
treatment
3.3.1.2   Detectable disease 
3.3.1.3   Age: ≤ 21 years of age
3.3.1.4   Estimated life expectancy of > 8 weeks
3.3.1.5   Prior to planned SJCAR19 infusion, patients with a history of prior 
allogeneic HCT must be at least 3 months from HCT, have no evidence of 
active GVHD and have not received a donor lymphocyte infusion (DLI) 
within the 28 days prior to planned infusion
3.3.1.6  Adequate cardiac function defined as left ventricular ejection fraction > 40%, 
or shortening fraction ≥ 25%
3.3.1.7  EKG without evidence of clinically significant arrhythmia 
3.3.1.8  Adequate renal function defined as creatinine clearance or radioisotope GFR 
 50 ml/min/1.73m2 (GFR  40 ml/min/1.73m2 if < 2 years of age) 
3.3.1.9  Adequate pulmonary function defined as forced vital capacity (FVC) ≥ 50% 
of predicted value; or pulse oximetry ≥  92% on room air if patient is unable to 
perform pulmonary function testing
3.3.1.10 Karnofsky or Lansky (age-dependent) performance score ≥ 50 (Appendix A)
3.3.1.11 Total Bilirubin ≤ 3 times the upper limit of normal for age, except in 
subjects with Gilbert’s syndrome
3.3.1.12 Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 
times the upper limit of normal for age
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3.3.1.13 Has recovered from all NCI CTAE grade III-IV, non-hematologic acute 
toxicities from prior therapy 
3.3.1.14 For females of child bearing age: 
• Not lactating with intent to breastfeed
• Not pregnant with negative serum pregnancy test within 7 days prior to 
enrollment
• If sexually active, agreement to use birth control until 6 months after T-
cell infusion. Male partners should use a condom
3.3.2
Exclusion Criteria for Treatment with SJCAR19
3.3.2.1
CNS-3 disease with or without neurologic changes 
3.3.2.2
CNS-1/CNS-2 disease with neurologic changes
3.3.2.3
Known primary immunodeficiency
3.3.2.4
History of HIV infection
3.3.2.5
Evidence of active, uncontrolled neurologic disease
3.3.2.6
Severe, uncontrolled bacterial, viral or fungal infection
3.3.2.7
History of hypersensitivity reactions to murine protein-containing products
3.3.2.8
Receiving systemic steroids therapy exceeding the equivalent of 0.5 
mg/kg/day of methylprednisolone, in the 7 days prior to CAR T-cell 
infusion (Appendix B)
3.3.2.9
Receiving systemic immunosuppressive therapy in the 14 days prior to CAR 
T-cell infusion, which will interfere with the activity of the SJCAR19 
product in vivo (in the opinion of the study PI(s)).
3.3.2.10 Receiving intrathecal chemotherapy in the 7 days prior to CAR T-cell 
infusion
3.4 Research Participant Recruitment and Screening
This study will be posted on http://clinicaltrials.gov. Potential patients are typically 
referred from their primary clinical service at St. Jude, from the Physician Referral Office 
for outside St. Jude patients, or are currently being treated by the Department of BMTCT. 
Each patient considered for therapy is registered on the “Transplant List,” an ongoing list 
used to provide the clinical service with information regarding new patients for 
consultation and under consideration for transplantation or cell therapy, and the status of 
those undergoing pre-evaluation. The patient remains on this list until a decision has been 
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confirmed for acceptance or rejection based on several factors, primarily completion of 
prior therapy and/or clinical status. The proposed patient schedules on this form are often 
subject to change due to various reasons such as family travel issues, donor availability 
for procurement of stem cells, recipient clinical status, etc. This list is a confidential 
document, updated and maintained by the Department of BMTCT Coordinators.
3.5 Enrollment on Study at St. Jude
A member of the study team will confirm potential participant eligibility as defined in 
Section 3.1-3.3, and register the participant in OnCore. Eligibility will be reviewed, and a 
research participant-specific consent form and assent document (where applicable) will 
be generated. The entire signed consent/assent form(s) must be either scanned and e-
mailed to protocoleligibilityoffice@stjude.org or faxed to the Clinical Trials Operations 
(CTO) office at 901-595-6265 to complete the enrollment process. Refer to St. Jude 
SOP39 “Eligibility and Consent Verfication Processes.”
To assist with enrollments and consent release, the CTO staff is available during office 
hours Monday – Friday. For help with patient enrollment after-hours, weekends, or 
holidays, please see the CTO intranet page for additional resources and instructions. 
Refer to St. Jude SOP CTO-TDOC-PE01 “Clinical Trials Management System 
Enrollment.”
4.0 TREATMENT PLAN
4.1 Overview of treatment process
This protocol contains a 3-part consent process. Patients that meet eligibility for 
autologous apheresis will be consented to undergo collection of autologous peripheral 
blood mononuclear cells (PBMC) via apheresis. Alternatively, patients whom have 
previously undergone autologous apheresis may be considered for enrollment on the 
manufacturing portion of the study if it is determined that their previously collected 
product is appropriate for use in manufacturing; these patients would therefore not need 
to be consented using the SJCAR19 apheresis consent.  When the patient meets eligibility 
criteria to begin manufacturing SJCAR19, they will be consented to proceed with 
manufacturing of the SJCAR19 product using their collected autologous cells. Lastly, 
when a SJCAR19 product has successfully been manufactured for an individual patient 
and they meet eligibility criteria to receive therapy with SJCAR19, they will be consented 
to proceed with the treatment portion of the study. 
Collected apheresis cells may be cryopreserved, or used fresh to generate the SJCAR19 
cell product. The SJCAR19 manufacturing process includes selection of T-cells from the 
apheresis product using a CliniMACS device, followed by activation and transduction of 
the selected T-cells. After transduction with the CD19-specific CAR lentivirus, T-cells 
will be expanded to the desired T-cell dose based on CAR+ T-cells. The final SJCAR19 
product will then be cryopreserved in treatment aliquots. After completion of quality 
assurance testing of SJCAR19, most patients will begin treatment with a lymphodepleting 
chemotherapy preparative regimen. This will be followed by a single infusion of 
SJCAR19, which will be administered thawed from frozen. Patients on the Phase II 
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study, who meet protocol defined criteria, may receive additional therapy with 
lymphodepleting chemotherapy and reinfusion of SJCAR19 (section 4.4.3).
See Appendix C for protocol flow chart. See Appendix D for a graphical summary of 
SJCAR19 manufacturing process. 
4.2 Cell Procurement, Processing and Infusion 
4.2.1 Autologous Apheresis and Storage

Patients will undergo evaluation for suitability and eligibility for apheresis in 
accordance with departmental guidelines.

The St. Jude Blood Donor Center of the Department of Pathology, accredited 
by both the American Association of Blood Bank (AABB) and Foundation for 
Accreditation of Cellular Therapy (FACT), and the Human Applications 
Laboratory of the Department of Therapeutic Production and Quality (TPQ), 
which is also FACT accredited, are responsible for the collection of the 
peripheral blood mononuclear cell (PBMC) product used in this protocol. 
Both groups are registered with the FDA and have established extensive 
quality assurance processes to ensure compliance with all Good 
Manufacturing Practice (GMP) and Good Tissue Practice (GTP) regulations. 
PBMC products will be collected as per current regulatory guidelines and 
established clinical practice procedures. Critical components include 
determination of donor eligibility, product tracking, manufacturing controls, 
documentation of lot production deviation investigations, product labeling, 
and release of products for use based on established lot criteria.  Reporting of 
applicable deviations or events to the IRB and/or the FDA is coordinated with 
the PIs and St. Jude Office of Regulatory Affairs.

The optimal timing of apheresis is not yet known. The timing of apheresis for 
each patient will be discussed with the collection team. 

It is recommended that patients undergo an unstimulated (no growth factors) 
collection of peripheral blood mononuclear cells (PBMC). 

It is suggested that prior to collection patients have:
o
An absolute lymphocyte count (ALC) ≥ 300/μL
o
CD3+ cell count ≥ 150/μL
o
Not received systemic steroids therapy exceeding the equivalent of 0.5 
mg/kg/day of methylprednisolone, in the 72 hours prior to apheresis
o
Not received systemic/intrathecal cytotoxic therapy in at least the 7 
days prior to apheresis. When possible, the timing should be extended 
for those who have received longer acting agents such as peg-
asparaginase 

The daily volume to be apheresed for PBMC collection is generally 3 − 4 total 
blood volumes.

Collection goals:
o
The goal collection is 2 x 109 total nucleated cells (TNC) and/or 1 x 
109 CD3+ cells
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
Apheresis will generally be performed on a single day. Additional days of 
collection will be done at the discretion of a transplant physician based on 
goal collection criteria. 

Apheresis may be terminated early upon the request of a patient/guardian, or 
when deemed medically necessary per the judgment of study investigators. 

The collected PBMC will be processed and stored in single or multiple 
aliquots as per the standard operating procedures of the St. Jude Human 
Applications Laboratory. 
4.2.2
CD19-specific CAR Lentiviral Production
A stable cell producer line for a lentivirus encoding CD19-CAR has been 
generated and vector lots are prepared by the St. Jude cGMP. The vector contains 
a chimeric antigen receptor consisting of a CD8 leader peptide, the CD19-specific 
single chain variable fragment (scFv) FMC63, the hinge and transmembrane 
domain of CD8 and the signaling domains of 4-1BB and CD3 under the control 
of a MND (myeloproliferative sarcoma virus enhancer, negative control region 
deleted, dl587rev primer-binding site substituted) promoter (Figure 3). 
Additionally, the 3’ partially-deleted viral LTR includes a 400-bp fragment from 
the chicken hypersensitive site 4 chromatin insulator element. The vector is self-
inactivating (SIN), derived from HIV. 
Figure 3:
4.2.3
SJCAR19 Production
The starting material for the SJCAR19 manufacturing process is an autologous 
apheresis product containing peripheral blood mononuclear cells (PBMC).  The 
PBMC are used fresh, or after being thawed and washed. T-cells are then selected 
using Militenyi’s CD8 and CD4 reagents using the CliniMACS™ system. The 
positively selected T-cells are then activated with GMP grade CD3 and CD28 
monoclonal antibodies or agonists, transduced with CD19-specific CAR lentiviral 
vector and expanded using cytokines. After the expansion period, the transduced 
T-cells are harvested, washed and pooled. After sampling for QC testing, the 
transduced T-cells are formulated for the cell dose in cryoprotectant and the cells 
are cryopreserved using a controlled rate freezer. The cryopreserved cells are 
stored in the vapor phase of liquid nitrogen. If more than the required number of i) 
cells are collected for SJCAR19 production, or ii) SJCAR19 cells are produced, 
detailed phenotypic and functional analyses as outlined in section 6.1.3 will be 
performed. In addition, samples might be used for studies to improve current cell 
processing procedures.
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4.2.4
Quality Assurance of the Cellular Product 
Products that meet study specific release criteria, as detailed on the Certificate of 
Analysis (CoA), will be infused as per Section 4.4. 
4.3 Bridging Chemotherapy

While the SJCAR19 cell product is being manufactured and released for 
clinical use, subjects may receive best clinical management bridging 
chemotherapy at the discretion of the primary oncologist in close consultation 
with a PI of this study. Bridging chemotherapy will be defined in a separate 
document requiring additional consent.

When choosing a regimen for an individual patient, the goal should be that the 
patient be expected to recover from any toxicities within 3 weeks of receipt of 
the bridging chemotherapy regimen.

Patients cannot receive intrathecal (IT) chemotherapy within 7 days of receipt 
of SJCAR19 product.

Patients should not receive blinatumomab as part of their bridging 
chemotherapy regimen.

Patients will be required to undergo repeat disease evaluation after completion 
of bridging chemotherapy, prior to beginning treatment with SJCAR19
4.4 SJCAR19 Therapy
4.4.1
SJCAR19 Treatment Schedule (initial infusion)
On both the Phase I and Phase II portions of the clinical study, patients will 
receive lymphodepleting chemotherapy* followed by infusion of SJCAR19 
(dosing in section 4.4.2). See Table 1 for example treatment schedule. 
Table 1: SJCAR19 Treatment Schedule (initial infusion)
DAY
MEDICATION*
DOSE
DOSE #
-4
Fludarabine
25 mg/m2 **
1 of 3
-3
Fludarabine
25 mg/m2 **
2 of 3
Fludarabine
25 mg/m2 **
3 of 3
-2
Cyclophosphamide
900 mg/m2 **
1 of 1
-1
REST DAY
0 or +1
SJCAR19 Infusion
Assigned dose 
1 of 1
*For patients that have contraindications to receiving fludarabine and/ or cyclophosphamide, in discussion 
with the PI of the study they may receive no lymphodepleting chemotherapy or an alternative regimen
**dose adjustment for patients < 10kg: Fludarabine 0.83 mg/kg/dose and Cyclophosphamide 30 mg/kg
General treatment related comments:

The term “day” does not refer to an absolute calendar day.  It refers to a 
general 24-hour period.

Dosing for the medications cyclophosphamide and fludarabine may be 
modified for research recipients based upon actual body weight or adjusted 
ideal body weight when clinically indicated. Mesna will be administered for 
prevention of hemorrhagic cystitis. 
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
Criteria for medication calculations based on body weight/body surface area 
and other medication related information can be found in the St. Jude 
Formulary http://www.crlonline.com/crlsql/servlet/crlonline or the St. Jude 
Department 
of 
Pharmaceutical 
Sciences 
intranet 
website 
http://home.web.stjude.org/pharmaceutical_ser/drugInfo.shtml. 
Medication 
doses may be rounded to the nearest integer or to the nearest appropriate 
quantity when clinically or pharmaceutically indicated as per the MD and 
PharmD. 
4.4.2
SJCAR19 Dosing and Initial Infusion
General treatment related comments:

Dosing of SJCAR19 is determined based on the number of CAR+ T cells 
in the SJCAR19 product and the patient weight in kilograms, with a 
maximum dose of 2.5 x 108 CAR+ T cells. 

SJCAR19 infusion will occur at least 36 hours after the completion of 
lymphodepleting chemotherapy.

At the time of SJCAR19 infusion, the subject should be afebrile and 
without active, uncontrolled infection. If fever is not responsive to anti-
pyretics, and not due to an identifiable infectious etiology, the patient may 
receive the SJCAR19 infusion in consultation with the study PI(s).

At the time of SJCAR19 infusion, the subject should be without evidence 
of rapidly progressive leukemia

Patients should be pre-medicated with Benadryl and/or Tylenol (dosing 
per institutional formulary) prior to infusion of SJCAR19, unless there is a 
medical contraindication against using either of these medications. 

SJCAR19 will be given thawed from frozen, as a single intravenous (IV) 
infusion.

For the proper infusion procedures and monitoring of the SJCAR19 
product please refer to BMTCT SOP 40.04.  Please note that all relevant 
SOPs can be found on the BMTCT Clinical Transplant Program intranet 
page: https://home.stjude.org/bmt/Pages/policies-transplant-program.aspx 

All patients shall receive the SJCAR19 infusion while inpatient. In the 
Phase I portion of the study, patients will remain inpatient for at least 7 
days post-infusion; in the Phase II portion of the study, patients will 
remain inpatient for at least 3 days post-infusion. At that time, discharge 
will be determined based on current clinical status. All patients shall 
remain locally until completion of week 4 study evaluations. 
Phase I treatment related comments:

On the Phase I portion of the study, up to 3 different dose levels will be 
evaluated (see Table 2), with a maximum dose of 2.5 x 108 CAR+ T cells. 
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
Escalation and de-escalation between dose levels will be determined by 
protocol defined dose-limiting toxicities (DLTs, see section 11.1).
Phase II treatment related comments:

On the Phase II portion of the study, all patients will receive the Phase I 
determined maximum tolerated dose (MTD) of SJCAR19, with a 
maximum dose of 2.5 x 108 CAR+ T cells.
4.4.3 Optional Reinfusion of SJCAR19 for Phase II Study Participants 
Phase II study participants that remain on-therapy and meet specified criteria will 
have the option to receive additional treatment courses. Treatment will consist of 
lymphodepleting chemotherapy and infusion of SJCAR19 cells, using 
cryopreserved manufactured product that was generated in excess of what was 
needed for the initial infusion. Patient may receive multiple treatment courses. 
4.4.3.1 Criteria for subsequent SJCAR19 infusions 

Autologous B-cell recovery within 6 months of prior infusion, defined as:
o
 ≥ 1% CD19+ cells in peripheral blood at 2 consecutive timepoints, at 
least 1 week apart 
AND/OR 
o
An absolute CD19+ count of ≥ 50/uL at a single timepoint
AND/OR

Recurrence of detectable leukemia within 12 months of prior infusion, 
defined as:
o
 < 5% morphologic blasts AND at least ≥ 0.01% blasts by flow 
cytometry, > 10-4 by PCR, and/or > 10-5  by NGS      
OR 
o
≥ 5% morphologic blasts with confirmation of disease by flow, RT-
PCR and/or NGS
Table 2: Phase I Dose Level Escalation of SJCAR19*
Dose Level
SJCAR19 Dose**
(Cells/kg)
-1
0.3 x 106
1
1 x 106
2
3 x 106
* +/- 20%
** the maximum dose of SJCAR19 is 2.5 x 108  CAR+ T cells 
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
If a participant is eligible for reinfusion based on one of the above two 
criteria, they must also meet the following conditions: For those with 
detectable leukemia: confirmation of CD19+ expression on leukemia 
blasts (exception: not feasible for those with disease detectable by only 
RT-PCR or NGS)

Prior complete response (MRD-positive or MRD-negative) to SJCAR19 
infusion as defined in Table 4 

At least 4-weeks since previous cell infusion

Meet all initial organ-function related eligibility criteria as outlined in 
section 3.3

Available cryopreserved SJCAR19 product at appropriate dosing 
4.4.3.2 Treatment (Reinfusion)

Participants may receive additional bridging therapy prior to reinfusion 
infusion of SJCAR19; regimen will be per treating physician discretion 
(section 4.3). While bridging therapy will not be given as part of the 
SJCAR19 study, patients will remain on-therapy/on-study. 

Treatment will follow section 4.4 with the following exceptions: 
o
Dosing of SJCAR19 reinfusion shall not be greater than the protocol 
defined MTD 
o
Participants will receive intensified lymphodepletion using the 
regimen below (Table 3); alternatively, in discussion with the PI the 
regimen may instead follow that as outlined in Table 1.
o
Table 3: Reinfusion: Intensified Lymphodepletion Regimen  
DAY
MEDICATION*
DOSE**
DOSE #
-4
Fludarabine
40 mg/m2 
1 of 3
Fludarabine
40 mg/m2 
2 of 3
-3
Cyclophosphamide
600 mg/m2 
1 of 2
Fludarabine
40 mg/m2 
3 of 3
-2
Cyclophosphamide
600 mg/m2 
2 of 2
-1
REST DAY
0 
SJCAR19 Reinfusion***
MTD
1 of 1
*For patients that have contraindications to receiving fludarabine and/or cyclophosphamide, 
in discussion with the PI of the study they may receive no lymphodepleting 
chemotherapy or an alternative regimen
**dose adjustment for patients < 10kg: Fludarabine 1.3 mg/kg/dose and Cyclophosphamide 
20 mg/kg
***Phase II cell dose: 3 x 106 CAR+ T cells/kg (+/- 20%); the maximum dose of SJCAR19 
is 2.5 x 108  CAR+ T cells
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4.4.3.3 Post-infusion monitoring

For each reinfusion treatment course, post-infusion monitoring will ‘start 
over’, following that as outlined for 1st infusions on the Phase II study. 
This includes but is not limited to:
o
Treatment evaluations (section 6.0; see also Appendices E and I; 
starting at week -1 time point) 
o
Response evaluations (section 7.0) 
o
Adverse event recording and reporting (section 9.0) 

Additionally, if two or more participants develop Grade 4 toxicity at any 
time following reinfusion, that is felt to be possibly, probably or likely 
related to the SJCAR19 product, then reinfusions will be paused pending 
discussion with the FDA and IRB regarding continuing to allow 
reinfusions.
4.4.3.4 Statistical considerations (Reinfusion):
Data from reinfusion may be included in safety, efficacy and exploratory 
analysis. This data will be collected as a unique infusion, adding 
additional data points, but not as a unique patient (i.e. reinfusion does not 
count towards enrollment goals).
4.5 Supportive Care
4.5.1
Venous Access
Chemotherapy and SJCAR19 will be given intravenously, either centrally or 
peripherally.
4.5.2
Allergic Reactions
Standard medications to treat allergic reactions should be available at the bedside 
prior to infusion of SJCAR19 (see BMTCT SOP 40.04).
4.5.3
Blood Product Support
Blood products are to be administered based on clinical status and the BMTCT 
SOP 50.06.
4.5.4
Fever and Neutropenia
Standard of care should be administered for complications resulting from 
neutropenia. Please refer to the St. Jude Institutional “Febrile Neutropenia in 
Patients with Cancer” Guidelines, which can be located on the St. Jude Intranet.
4.5.5
Cytokine Release Syndrome
Cytokine release syndrome (CRS) is a commonly reported toxicity with treatment 
with CD19-specific CAR-T cells. Patients will be closely monitored for signs and 
symptoms of CRS, and treatment guided by BMTCT SOP 20.15. The goal of 
interventions should be to prevent life-threating consequences of CRS, while 
attempting to preserve the anti-tumor benefits of SJCAR19.
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4.5.6
Neurotoxicity
Neurotoxicity is a commonly reported side effect of treatment with CD19-specific 
CAR-T cells. Patients will be closely monitored for signs and symptoms of 
neurotoxicity, and treatment guided by BMTCT SOP 20.15. The goal of 
interventions should be to prevent life-threating consequences of neurotoxicity, 
while attempting to preserve the anti-tumor benefits of SJCAR19. 
4.5.7
Hypogammaglobinemia
During the period of B-cell aplasia, supportive care will include giving 
participants intravenous immunoglobulins (IVIG) if their IgG level is lower than 
400 mg/dl.
4.6 Concomitant therapy and/or enrollment onto therapeutic protocols post-infusion of 
SJCAR19
Participants will not be allowed to receive concomitant therapy for primary disease or 
high dose steroids (> 0.5 mg/kg/day methylprednisolone equivalent; see Appendix B) 
during the first 4 weeks after SJCAR19 infusion. A disease status evaluation will be 
conducted approximately 4 weeks post-SJCAR19 infusion. If at this time complete 
response is not achieved, the participant will be allowed to receive chemotherapy or 
enroll onto a therapeutic study for their disease if available. 
5.0 DRUG/DEVICE/BIOLOGIC AGENT INFORMATION
5.1 Medications
Cyclophosphamide (Cytoxan)
Source & 
Pharmacology
Cyclophosphamide is a nitrogen mustard derivative.  It acts as an alkylating 
agent that causes cross-linking of DNA strands by binding with nucleic acids and 
other intracellular structures, thus interfering with the normal function of DNA. 
It is cell cycle, phase non-specific. Cyclophosphamide is well absorbed from the 
GI tract with a bioavailability of >75%.  It is a prodrug that requires activation. It 
is metabolized by mixed function oxidases in the liver to 4-hydroxycyclo-
phosphamide, which is in equilibrium with aldophosfamide. Aldofosfamide 
spontaneously splits into nitrogen mustard, which is considered to be the major 
active metabolite, and acrolein. In addition, 4-hydroxycy-clophosphamide may 
be enzymatically metabolized to 4-ketocyclophosphamide and aldophosfamide 
may be enzymatically metabolized to carboxyphosphamide that is generally 
considered inactive.  Cyclophosphamide and its metabolites are excreted mainly 
in the urine. Dose adjustments should be made in patients with a creatinine 
clearance of <50 ml/min.
Formulation 
and Stability
Cyclophosphamide is available in vials containing 100, 200, 500, 1000 and 
2000mg of lyophilized drug and 75 mg mannitol per 100 mg of 
cyclophosphamide. Both forms of the drug can be stored at room temperature. 
The vials are reconstituted with 5, 10, 25, 50 or 100 ml of sterile water for 
injection, respectively, to yield a final concentration of 20 mg/ml.  Reconstituted 
solutions may be further diluted in either 5% dextrose or 0.9% NaCl containing 
solutions. Diluted solutions are physically stable for 24 hours at room 
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temperature and 6 days if refrigerated, but contain no preservative, so it is 
recommended that they be used within 24 hours of preparation.
Supplier
Commercially available
Toxicities
Dose limiting toxicities of cyclophosphamide includes BM suppression and 
cardiac toxicity. Cardiac toxicity is typically manifested as congestive heart 
failure, cardiac necrosis or hemorrhagic myocarditis and can be fatal.  
Hemorrhagic cystitis may occur and necessitates withholding therapy. The 
incidence of hemorrhagic cystitis is related to cyclophosphamide dose and 
duration of therapy. Forced fluid intake and/or the administration of Mesna 
decreases the incidence and severity of hemorrhagic cystitis.  Other toxicities 
reported commonly include nausea and vomiting (may be mild to severe 
depending on dosage), diarrhea, anorexia, alopecia, immunosuppression and 
sterility.  Pulmonary fibrosis, SIADH, anaphylaxis and secondary neoplasms 
have been reported rarely.   
Route 
Intravenous infusion 
Fludarabine (Fludara)
Source & 
Pharmacology 
Fludarabine phosphate is a synthetic purine nucleoside analog.  It acts by 
inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by 
competing with the physiologic substrate, deoxyadenosine triphosphate, resulting 
in inhibition of DNA synthesis. In addition, fludarabine can be incorporated into 
growing DNA chains as a false base, thus interfering with chain elongation and 
halting DNA synthesis.  Fludarabine is rapidly dephosphorylated in the blood 
and transported intracellularly via a carrier-mediated process. It is then 
phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate 
form.  Approximately 23% of the dose is excreted as the active metabolite in the 
urine (with dosages of 18-25 mg/m2/day for 5 days). Renal clearance appears to 
become more important at higher doses, with approximately 41-60% of the dose 
being excreted as the active metabolite in the urine with dosages of 80-260 
mg/m2.
Formulation 
and Stability
Fludarabine is supplied in single-dose vials containing 50 mg fludarabine as a 
white lyophilized powder and 50 mg of mannitol.  The intact vials should be 
stored under refrigeration. Each vial can be reconstituted by adding 2 ml of 
sterile water for injection resulting in a final concentration of 25 mg/ml. Because 
the reconstituted solution contains no antimicrobial preservative, the 
manufacturer recommends that it should be used within 8 hours of preparation. 
The solution should be further diluted in 5% dextrose or 0.9% NaCl prior to 
administration.
Supplier
Commercially available.
Toxicities
The major dose-limiting toxicity of fludarabine is myelosuppression.  Nausea 
and vomiting are usually mild.  Side effects reported commonly include 
anorexia, fever and chills, alopecia and rash.  Neurotoxicity can be manifested by 
somnolence, fatigue, peripheral neuropathy, mental status changes, cortical 
blindness and coma and is more common at high doses.  Neurotoxicity is usually 
delayed, occurring 21-60 days after the completion of a course of therapy and 
may be irreversible.  Side effects reported less commonly include diarrhea, 
stomatitis, increased liver function tests, liver failure, chest pain, arrhythmias and 
seizures.  Pulmonary toxicity includes allergic pneumonitis characterized by 
cough, dyspnea, hypoxia and pulmonary infiltrates.  Drug induced pneumonitis is 
a delayed effect, occurring 3-28 days after the administration of the third or later 
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course of therapy. Administration of corticosteroids usually results in resolution 
of these symptoms.
Route   
Intravenous
Mesna (Mesnex)
Source & 
Pharmacology 
Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free 
sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-
phosphorine derivatives such as cyclophosphamide and ifosfamide. Oral 
bioavailability is 50%. Upon injection into the blood, Mesna is oxidized to 
Mesna disulfide, a totally inert compound. Following glomerular filtration, 
Mesna disulfide is rapidly reduced in the renal tubules back to Mesna, the active 
form of the drug.  Mesna and Mesna disulfide are excreted primarily via the 
urine.
Formulation 
and Stability
Mesna is available in 2 ml, 4 ml and 100 ml amps containing 100 mg/ml of 
Mesna solution. The intact vials can be stored at room temperature.  Mesna may 
be further diluted in 5% dextrose or 0.9% NaCl containing solutions.  Diluted 
solutions are physically and chemically stable for at least 24 hours under 
refrigeration.  
Supplier
Commercially available
Toxicities
Mesna is generally well tolerated. Nausea and vomiting, headache, diarrhea, 
rash, transient hypotension and allergic reactions have been reported.  Patients 
may complain of a bitter taste in their mouth during administration. Mesna may 
cause false positive urine dipstick readings for ketones.  
Dosage and 
Administration
Mesna is generally dosed at approximately 25% of the cyclophosphamide dose.  
It is generally given intravenously prior to and again at 3, 6 and 9 hours 
following each dose of cyclophosphamide.
Route
Intravenous
5.2 CliniMACSTM System  
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-
activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation 
of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can 
then be separated in a magnetic field using an immunomagnetic label specific for the cell 
type of interest, such as CD4+ or CD8+ human T cells. The basic mechanism is the same 
for either application; target cells are "tagged" with super-paramagnetic particles and 
eventually separated from the unlabeled cells using the CliniMACS device as described 
above. The desired target cells can either be infused or discarded appropriately. The 
CliniMACS device is not licensed by the FDA for CD4 or CD8 selection, and therefore is 
investigational.
The CliniMACS device is comprised of a computer controlled instrument incorporating a 
strong permanent magnet, a closed-system sterile tubing set containing columns with a 
coated ferromagnetic matrix and a paramagnetic, cell specific, labeling reagent. Cells are 
labeled with antibody-conjugated beads that target a surface maker of interest. The 
monoclonal antibody is conjugated to a super-paramagnetic particle that is small in size 
(about 50 nm in diameter) and composed of iron oxide/hydroxide and dextran. These 
magnetic particles form a stable colloidal solution and do not precipitate or aggregate in 
magnetic fields.  The antibody conjugated beads used in this system are highly specific 
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(e.g. CD4+ and CD8+ conjugated beads). High-gradient MACS technology has been 
shown to achieve rapid and highly specific depletion or enrichments of large numbers of 
target cells from bone marrow, cord blood, and normal peripheral blood mononuclear 
cells. The CliniMACS device incorporates a strong permanent magnet and a separation 
column with a ferromagnetic matrix to separate the cells labeled with the magnetic 
particles. The high-gradient system allows the application of strong magnetic forces and a 
rapid de-magnetization. Small ferromagnetic structures, such as the column matrix, 
placed in a magnetic field concentrate this homogenous field and thereby produce high 
magnetic gradients. In their immediate proximity, the ferromagnetic structures generate 
magnetic forces 10,000-fold greater than in the absence of those structures enabling the 
retention of magnetically labeled cells. After removing the column from the magnet, the 
rapid de-magnetization of the column matrix allows the release of retained cells.
6.0 REQUIRED EVALUATIONS, TESTS, AND OBSERVATIONS
At the time of autologous apheresis, information regarding the patient’s current clinical 
status will be recorded. Studies looking at the immunologic content of the apheresis and 
SJCAR19 products will be performed.
 
Once the patient proceeds with the treatment portion of the protocol, and for all 
reinfusions, a complete history, physical examination, and performance status is 
necessary prior to lymphodepletion (week -1) and SJCAR19 administration (week 0). A 
complete history, physical exam and performance status will be collected at week 1, 2, 3, 
4, and 8. A complete history will continue to be collected every three months for a year. 
Starting week 8, contact by the investigator or research nurse/research coordinator by 
phone or email may substitute for history if the patient is unable to return to clinic. The 
week 8 physical examination and performance score can also be completed by the 
patient’s local treatment team if the patient is unable to return to St. Jude for evaluation. 
All patients shall receive the SJCAR19 infusion while inpatient. In the Phase I portion of 
the study, patients will remain inpatient for at least 7 days post-infusion; in the Phase II 
portion of the study (for initial and reinfusions), patients will remain inpatient for at least 
3 days post-infusion. At that time, discharge will be determined based on current clinical 
status. All patients shall remain locally until completion of week 4 study evaluations. 
6.1 Treatment Evaluations
All evaluations are summarized in the study calendar provided in Appendix E. Daily 
maximum blood draw will follow institutional standards. 
6.1.1
Standard Laboratory Investigations

CBC and differential: pre-lymphodepleting chemotherapy (wk -1), post-
lymphodepleting chemotherapy but pre-SJCAR19 infusion (wk 0), at 1, 2, 
3, 4 and 8 weeks and then at 3, 6, 9, and 12 months post-SJCAR19 
infusion. 
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
BUN, Creatinine, Na+, K+, Cl-, CO2, Mg, P: pre-lymphodepleting 
chemotherapy (wk -1), post-lymphodepleting chemotherapy but pre-
SJCAR19 infusion (wk 0), at 1, 2, 3, 4 and 8 weeks post-SJCAR19 
infusion.

AST/ALT, Bilirubin, Albumin: pre-lymphodepleting chemotherapy (wk -
1), post-lymphodepleting chemotherapy but pre-SJCAR19 infusion (wk 
0), at 1, 2, 3, 4 and 8 weeks post-SJCAR19 infusion.

CRP, Ferritin: pre-lymphodepleting chemotherapy (wk -1), post-
lymphodepleting chemotherapy but pre-SJCAR19 infusion (wk 0), at 1, 2, 
3, 4 and 8 weeks post-SJCAR19 infusion.

Lymphocyte Subset Panel: pre-lymphodepleting chemotherapy (wk -1), at 
4 and 8 weeks and then at 3, 6, 9, and 12 months post-SJCAR19 infusion.

Quantitative Immunoglobulins: pre-lymphodepleting chemotherapy (wk -
1), at 4 and 8 weeks and then at 3, 6, 9, and 12 months post-SJCAR19 
infusion.

Serum pregnancy test will be performed within the week preceding 
starting pre-lymphodepleting chemotherapy (wk -1) on female patients of 
child bearing potential unless they have no possibility of pregnancy (for 
example post hysterectomy).

Other tests: Infectious disease testing will be done at the time of blood 
procurement for SJCAR19 production.

Additional routine laboratory investigations may be performed as per 
institutional guidelines during the administration of lymphodepleting 
chemotherapy.
6.1.2
Other Laboratory Testing 

Serum from blood drawn at week 0 and week 4 will be stored for 
measurement of Human anti-mouse antibodies (HAMA) in the event of a 
suspected immunologic reaction.
6.1.3
SJCAR19 Research Laboratory Testing
All of these tests may not be performed on every specimen as a limited 
number of cells will be available. In general, priority will be given to PCR 
assays to detect for the presence of SJCAR19. Additional samples may be 
sent if the patient has concern for disease relapse/progression, or an acute 
clinical change that is felt to possibly be related to the SJCAR19 product 
(see section 6.1.6). Furthermore, research laboratory testing may also be 
performed using a leftover clinically indicated sample.
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SJCAR19 Research Labs:
Persistence/Functional studies:

Quantitative real-time PCR 

FACS analysis 

If detection of SJCAR19 is greater than 0.5% via FACS and 
there is persistent SJCAR19 expansion 3 months after T-cell 
infusion, we will perform clonality studies (an extra 5 ml of 
blood). Further evaluations may be done based on clinical 
decisions. 

Persistence and/or Functional studies may include studies such 
as: phenotypic subset characterization, functional correlates 
(e.g. Elispot assay, PCR to determine viral load), methylation 
analysis, multipotency indices, analysis of the epigenetic 
signatures, TCR repetiore analysis, VIS analysis and single cell 
analysis such as RNA seq.
Persistence and/or Functional Studies may be performed on peripheral 
blood, bone marrow aspirate, or CSF to monitor function, persistence and 
safety of SJCAR19 and unmodified immune cells at time-points indicated 
in the study calendar. 
Samples to be obtained on peripheral blood pre-lymphodepleting 
chemotherapy (wk -1), post-lymphodepleting chemotherapy but pre-
SJCAR19 infusion (wk 0), 1 to 4 hours post infusion, 3 - 4 days post 
infusion (optional per discretion of PI/Transplant Attending), at 1, 2, 3, 4 
and 8 weeks, and then at 3, 6, 9, and 12 months. 
Cytokine studies:

Samples for serum or plasma cytokines/chemokines levels will 
be obtained, and stored, at the following time points: pre-
lymphodepleting chemotherapy (wk -1), post-lymphodepleting 
chemotherapy but pre-SJCAR19 infusion (wk 0), 1 to 4 hours 
post infusion, 3 - 4 days post infusion (optional per discretion 
of PI/Transplant Attending), and at 1, 2, 3, 4 and 8 weeks. 
Beginning at wk 2, analysis will be optional based on the 
clinical course of each patient (per discretion of the study PIs).
Microenvironment and leukemia blast studies:
For evaluation of tumor microenvironment and leukemia blasts, we will 
collect a sample at the 4-week post-CAR T-cell infusion disease 
evaluation. If a patient has circulating peripheral blood blasts at any time 
while on study, this analysis may also be performed on that study sample. 
Analysis 
may 
also 
be 
performed 
on 
prior 
banked 
tumor 
samples/diagnostic samples, including the most recent marrow sample 
pre-CAR therapy, or through comparison to existing genomic data. 
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
Analysis for microenvironment and leukemia blast studies may 
include: flow cytometry, single cell RNAseq, and genomic, 
transcriptomic and proteomic analysis.
6.1.4
Other Testing

To assess cardiac function, an echocardiogram (ECHO) and EKG will be 
performed within 2 weeks of starting lymphodepleting chemotherapy 
regimen.

An 
additional 
EKG 
will 
be 
performed 
post-lymphodepleting 
chemotherapy but pre-SJCAR19 infusion (wk 0).
6.1.5 Evaluation for Leukemic Disease 
Minimal residual disease (MRD) assays will be performed in the bone 
marrow, cerebrospinal fluid (CSF) and/or peripheral blood by immunologic 
and molecular methods.  For all patients, MRD will be assessed for by flow 
cytometry if they have MRD that is able to be followed by flow. For those 
patients that have disease that is able to be followed by PCR testing, this 
testing will also be performed, either in lieu of flow if flow is not available, 
or in addition to flow cytometry methods. Tests will be performed using 
flow, PCR and/or next generation sequencing (NGS). 

Peripheral blood MRD: within 2 weeks prior to start of lymphodepleting 
chemotherapy (after receipt of any bridging chemotherapy and before 
protocol 
pre-lymphodepleting 
chemotherapy), 
post-lymphodepleting 
chemotherapy but pre-SJCAR19 infusion (wk 0), and at 4 weeks and 3 
months post SJCAR19 infusion. 

Bone marrow aspirates: within 2 weeks prior to start of lymphodepleting 
chemotherapy (after receipt of any bridging chemotherapy and before 
protocol pre-lymphodepleting chemotherapy), and at 4 weeks and 3 
months post-SJCAR19 infusion. 

CSF: within 2 weeks prior to start of lymphodepleting chemotherapy (after 
receipt of any bridging chemotherapy and before protocol pre-
lymphodepleting chemotherapy) and at 4 weeks post-SJCAR19 infusion. 
For patients with recent history of CNS disease, sample also to be 
obtained at 3 months post-SJCAR19 infusion. 

For patients who get additional clinical evaluations related to monitoring 
for leukemic disease (such as PET-CT or biopsy), results will be recorded. 
6.1.6 Other tissue samples
For any additional tissue sample that is obtained while the patient is on this 
study to determine their diseases status, we will obtain an extra sample for 
testing as described in section 6.1.3.
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
For any patients who die or develop a second neoplasm, significant 
hematologic or neurologic disorder during the trial, a biopsy sample of the 
neoplastic tissue or pertinent autopsy tissue will be assayed by PCR for 
presence of the SJCAR19 transgene (if a sample can be obtained).
6.1.7 Evaluation for RCL
RCL testing will be performed pre-lymphodepleting chemotherapy (wk -1) 
and 3, 6, and 12 months post-SJCAR19 infusion. 
6.2 Patient Reported Outcomes and Quality of Life Evaluations
All questionnaires aimed at assessing patient QoL can be administered directly to the 
patient or to a caregiver proxy. We will attempt to obtain patient data at every 
opportunity, i.e. when the patient is of an appropriate age to complete the measure 
based on prior validation studies and when the patient is medically able to complete 
the measure. We will also attempt to obtain proxy data for each questionnaire at each 
time point in anticipation of the likelihood that a significant proportion of patients 
may be medically unable to participate at one or more time points. Having consistent 
proxy measures will allow for ease of longitudinal comparison over time. Data will be 
obtained from patients and caregivers independently such that if one or the other is 
unable to participate, data can still be collected from the available participant. For 
Spanish-speaking participants, validated Spanish language questionnaires will be 
administered when available. If a validated Spanish questionnaire is not available, the  
questionnaire will not be administered.  
The semi-structured interviews will be conducted with English-speaking patients and 
caretakers. Both parties will be engaged in the questions and answers from all 
participants will be recorded and transcribed for analysis. Semi-structured interviews 
will not be conducted with non-English-speaking particpants. 
All components of the quality of life evaluation can be administered over the phone. 
Every effort will be made to obtain questionnaire data and perform semi-structured 
interviews in person, but if this is not feasible all data can be collected by phone. 
All evaluations are summarized in the study calendar provided in Appendix I. 
6.2.1
Symptom Assessment
PRO-CTCAE, Core Terms: This is a 15-item Likert-type scale developed to assess 
adverse events, their severity/frequency, and the degree of consequent functional 
impairment. For participants < 7 years of age, we will ask that the primary 
caretaker complete the Proxy PRO-CTCAE. Participants 7 to 15 years of age will 
complete the Pediatric PRO-CTCAE, with help of research staff as needed. 
Participants aged 16 years or older will complete the Adult PRO-CTCAE.  This 
measure is available in both English and Spanish. 
6.2.2 Evaluation of Patient Quality of Life
The Pediatric Quality of Life Inventory (PedsQL V.4): This is a 23-item Likert-
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type scale developed to measure health-related QOL in children and adolescents. It takes 
about 4 to 6 minutes to complete. This instrument has a form for caregivers, including 
both the acute (QoL within the past 7 days) and chronic (QoL within the past 30 days) 
forms. Subscales on the PedsQL V.4 measure the research participant’s physical, 
emotional, social, and school functioning. The forms have been found to be internally 
consistent (Cronbach alpha coefficients of 0.92). They were also shown to have clinical 
validity (i.e., able to distinguish between known groups of research participants on and 
off therapy), and to allow construct validity (i.e., hypotheses predicting relationships 
between certain subscales and other indicators of emotional distress, perceived 
competency, social support/functioning, and academic competence were supported). This 
measure is available in both English and Spanish. 
The PedsQL Cancer Module V.3: This is a 27-item Likert-type questionnaire that 
involves 8 subscales relevant to the pediatric cancer experience: 1) pain and hurt, 
2) nausea, 3) procedural anxiety, 4) treatment anxiety, 5) worry, 6) cognitive 
problems, 7) perceived physical appearance, and 8) communication. This measure 
is available in both English and Spanish. 
Good Day Bad Day Scale: This is a qualitative instrument that will ask two 
questions to the research participants: “What makes a good day for you?” and 
“How has being sick been for you?” This semi-structured interview will only be 
conducted with English-speaking participants.
Qualitative Symptoms Assessment: Through semi-structured interviews, patients 
will also be asked to identify their most bothersome or worrying symptoms. 
Trained interviewers will then probe with follow-up questions to understand 
exactly what symptoms patients are experiencing, the severity of these symptoms, 
and to what degree they interfere with daily function. Interview will also probe 
what patient and caregivers recall from earlier consent conversations re: study 
participation and signs and symptoms. We will explore whether anticipatory 
guidance about side effects and risks was helpful for patients that went on to 
experience those side effects. This semi-structured interview will only be 
conducted with English-speaking participants.
6.2.3 Evaluation of Caretaker Well-being and Quality of Life
The Caregiver Quality of Life Index – Cancer (CQOLC)82: This is a 35-item 
questionnaire to assess QoL of the family caregiver of each research participant. It 
can be completed in 10 minutes. The items assess the caregiver's overall mental 
health, emotional distress, physical health, social support, social desirability, as 
well as the research participant’s performance status and related caregiver QoL. 
The instrument has been found to have adequate validity, test-retest reliability 
(0.95) and internal consistency (Cronbach's alpha coefficient of 0.91). This 
measure is available in both English and Spanish. 
The Functional Assessment of Chronic Illness Therapy – Spiritual Well-Being 
(FACIT-Sp-12)83: This is a 12-item Likert-type scale to measure one’s sense of 
meaning, harmony, peacefulness, and a sense of comfort and strength. It requires 
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5 to 6 minutes to be completed. It has been found to have good psychometric 
properties in assessing the spiritual well-being of people with cancer and their 
caregivers and is the most commonly used clinical research tool to assess spiritual 
well-being, an important factor in overall and health-related quality of life. This 
measure is available in English and Spanish.
The Hospital Anxiety and Depression Scale84: This is a 14-item Likert scale 
developed to assess the cognitive symptoms of anxiety and depression. 
Psychometric properties of this scale have supported the use of this tool among 
research participants and family caregivers. The internal consistency of the 
anxiety and depression scale was good (Cronbach’s alpha coefficients of 0.83 and 
0.82). This scale was also sensitive and specific. It can be completed in 6-7 
minutes. This measure is only available in English. 
The Herth Hope Index (HHI)84, 85: This is a 12-item Likert scale developed to 
assess hope in adults in clinical settings. The scale is adapted from the Herth 
Hope Scale (HHS) and has a Cronbach's alpha coefficient of 0.97 with a two – 
week test – retest reliability of 0.91. Criterion-related validity ranges from r = 
0.92 to r = 0.73. This scale has been used extensively in the clinical setting. It can 
be administered in 5 to 6 minutes and can be scored easily and reliably. This 
measure is available in English and Spanish.
The Modified Parent-Patient Activation Measure (mP-PAM)86: This is a 13-item 
Likert-like scale developed to assess degree of caregiver knowledge, skill, and 
confidence for self-management. The internal consistency of this scale is good 
(Cronbach’s alpha coefficient of 0.90 in English-speaking populations). It has 
been modified from its original version to address issues facing the pediatric 
cancer population.  This measure is only available in English.
6.3 Long-term Follow-up Evaluations
Long-term follow-up will occur for 15 years as per FDA guidance. Follow-up will 
occur on protocol for the first year after the last SJCAR19 infusion. After one year, 
patients will be approached and consented to the current institutional long-term 
follow-up protocol for patients treated with genetically modified cell therapy 
products. ). If a patient does not enroll on this long-term follow-up protocol, we will 
continue to monitor patients on-study, for up to 15 years post-infusion, per current 
FDA guidance (‘Long Term Follow-Up after Administration of Human Gene Therapy 
Products’ and ’Testing of Retroviral Vector-Based Human Gene Therapy Products 
for Replication Competent Retrovirus During Product Manufacture and Patient 
Follow-up’). 
7.0 EVALUATION CRITERIA
7.1 Toxicity Evaluation Criteria
Adverse event (AE) monitoring for on-study research participants will be assessed using the 
NCI Common Terminology Criteria for Adverse Events Version 5.0. The standard 
procedures for adverse event collection and monitoring are noted in Appendix F. An 
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exception will be made with the staging and grading of CRS and neurotoxicity, which will 
be assessed and graded using the ASTCT consensus grading system (Appendix G and H)..
7.2 Disease Response Criteria
Disease response criteria will based on the level of disease a patient has prior to treatment 
with SJCAR19. Response will be determined at 4 weeks post-SJCAR19 infusion based 
on disease status in a bone marrow sample. For all patients, MRD will be assessed for by 
flow cytometry if they have MRD that is able to be followed by flow. For those patients 
that have disease that is able to be followed by PCR testing or NGS testing, this testing 
will also be performed, either in lieu of flow if flow is not available, or in addition to flow 
cytometry methods. MRD is defined as leukemia detection via flow of > 0.01%, PCR of 
> 10-4, and/or NGS of > 10-5. See Table 4 for disease response criteria.
Table 4: Disease Response Criteria
Patient disease status at enrollment
MRD-positive disease
< 5% blasts, morphologic, 
bone marrow
AND
> 0.01% blasts by flow 
cytometry, > 10-4 by PCR, 
and/or > 10-5  by NGS
Low-Burden 
disease
> 5% to < 25% 
blasts, morphologic, 
bone marrow
High Burden 
Disease
> 25% blasts, 
morphologic, bone 
marrow
Patient disease status after treatment 
with SJCAR19
< 5% blasts by morphologic evaluation of 
the bone marrow
AND
< 0.01% blasts by flow cytometry, < 10-4 
by PCR, and/or < 10-5  by NGS
Complete Response, 
MRD-negative
Complete Response, 
MRD-negative
Complete Response, 
MRD-negative
< 5% blasts by morphologic evaluation of 
the bone marrow
AND
> 0.01% blasts by flow cytometry, > 10-4 
by PCR, and/or > 10-5  by NGS
No Response
Complete Response, 
MRD-positive
Complete Response, 
MRD-positive
5% to 25% blasts by morphologic 
evaluation of the bone marrow, with 
confirmation by flow cytometry, PCR, 
and/or NGS
Progressive Disease
No Response
Partial Response
25% blasts by morphologic evaluation of 
the bone marrow, with confirmation by 
flow cytometry, PCR, and/or NGS
Progressive Disease
Progressive Disease
No Response
For participants who achieved remission 
after SJCAR19 infusion, the new finding 
of   5% leukemic blasts in the bone 
marrow, >0.01% blasts by flow cytometry 
≥ 10-4 by  PCR, > 10-5  by NGS or the 
development of extramedullary disease 
Relapse
Relapse
Relapse
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8.0 CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF-STUDY 
CRITERIA
8.1 Off Study Criteria
Recipient research participants will remain on study until one of the following occurs:
8.1.1
Withdrawal from protocol.
8.1.2
Death.
8.1.3
If patient eligible and consented to a portion of the protocol, but then is 
found to be ineligible for subsequent portions of the protocol. 
8.1.4
Positive pregnancy test after enrolling in the protocol, but prior to 
receiving the study infusion.
8.1.5
Development of a significant change in health status at any point in 
therapy, which in the judgment of the clinical PI, would render 
continuation in the study medically unsafe or not in the participant’s best 
interest 
8.1.6
Unable to be contacted and/or effectively monitored by the Principal 
Investigator (PI) and/or designees for follow-up (lost to follow-up).
8.1.7
One-year after the last SJCAR19 infusion AND enrollment in the St. Jude 
long-term follow-up protocol for genetically modified cell therapy 
products.
8.1.8
Completion of long-term follow-up per FDA guidance.
8.2 Off Therapy Criteria
Recipient research participants may remain on study for monitoring of relapse, death and 
RCL, but be considered off therapy, if one of the following occurs: 
8.2.1
Noncompliance with protocol medications/administrations and/or required 
follow-up evaluations. 
8.2.2
Treatment on a therapeutic study or non-protocol treatment plan, or receipt 
of anti-leukemia therapy that is not specifically defined in this protocol, 
that would render the ongoing study of the SJCAR19 product or its 
toxicities no longer relevant (in the opinion of the study PIs). *Exception – 
need for bridging therapy for patients preparing for reinfusion of the 
SJCAR19 product.
8.2.3
Development of an unacceptable toxicity, which in the opinion of the 
clinical PI(s), would render continued participation harmful.
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8.2.4
Receipt of any therapy during the initial 4 week evaluation period that 
could interfere with the SJCAR19 product in vivo (ex- chemotherapy, 
systemic steroids), except if that therapy is for the treatment of toxicity 
that is felt to be due to the SJCAR19 therapy.
9.0 SAFETY AND ADVERSE EVENT REPORTING REQUIREMENTS
9.1 Reporting Adverse Events and Deaths to St. Jude IRB
The principal investigator(s) is responsible for promptly reporting to the IRB any 
adverse events that are unexpected/unanticipated, serious, and that may represent 
potential harm or increased risk to research participants. When an unexpected death 
occurs, the PI should report it to the Director of Human Subject’s Protection 
immediately, by phone: (901) 595-4359, cell: (901) 336-2894, fax: (901) 595-4361, 
or e-mail: hsp-1@stjude.org.  A reportable event entry into iRIS should follow within 
48 hours of notification of the event.
Serious, unexpected, and related, or possibly related, events must be reported within 
10 business days of notification of the event. At the same time, the investigator will 
notify the FDA, as appropriate. All other SAEs, including expected death, and all 
captured AEs will be reported to the IRB at the time of the continuing reviews, with 
the exceptions of dose limiting toxicities defined in Table 5 (section 11.2).
For Phase I: Data on all adverse experiences/toxicities regardless of seriousness 
must be collected for documentation purposes. 
For Phase II (initial and any reinfusions): Data on adverse events ≥ grade 3 will be 
recorded. In addition, clinically significant grade 1-2 adverse events that are judged to 
be related/possibly related to the CAR T-cell product may be collected per the 
discretion and judgment of the PI. Examples could include but are not limited to: 
events meeting criteria for SAE and infections requiring oral systemic therapy.
For both Phase I/II: In accordance with our institutional practice, data will be 
collected on related AEs for 7 days after the apheresis procedure. AE collection will 
then resume for the treatment portion of the study, beginning on the day of starting 
lymphodepleting chemotherapy and continuing for 4 weeks post-SJCAR19 infusion. 
Collection of AEs related to CRS and/or neurotoxicity will continue to be collected 
until the 3 month time point after the last SJCAR19 infusion. Reporting of serious 
adverse events related to gene transfer will occur initially  on protocol for 1 year after 
the last SJCAR19 infusion, and then continue as part of our existing institutional 
long-term follow-up protocol or on SJCAR19 for patients who do not enroll on this 
LTFU study.
The criteria listed in the NCI Common Toxicity Criteria Scale will be used in grading 
toxicity (Version 5.0 located at http://ctep.cancer.gov) with the exception of CRS and 
St. Jude Children's Research Hospital
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neurological toxicities that are related to SJCAR19. CRS and neurological toxicities 
will be graded according to Appendices G and H.
The following definitions apply with respect to reporting adverse experiences: 
Serious adverse event – any adverse event temporally associated with the 
participant’s participation in research that meets any of the following criteria:

results in death;

is life-threatening (places the participant at immediate risk of death from the 
event as it occurred);

requires inpatient hospitalization or prolongation of existing hospitalization

results in a persistent or significant disability/incapacity;

results in a congenital anomaly/birth defect; or

any other adverse event that, based upon appropriate medical judgment, may 
jeopardize the participant’s health and may require medical or surgical 
intervention to prevent one of the above outcomes.
Unexpected adverse event – any adverse event meeting any of the following criteria:

an event for which the specificity or severity is not consistent with the 
protocol related documents, including the applicable investigator brochure, 
IRB approved consent form, IND application or any of the product labeling or 
package inserts;

an event for which the observed rate of occurrence is significantly increased 
above what is expected or credible baseline rate for comparison;

an event for which the occurrence is not consistent with the expected natural 
progression of any underlying disease, disorder, or condition of the 
participant(s) experiencing the adverse event and the participant’s 
predisposing risk factor profile for the adverse event.
The principal investigator(s) is responsible for reviewing the aggregate toxicity 
reports and reporting to the IRB if the frequency or severity of serious toxicities 
exceed those expected as defined in the protocol or based on clinical experience or 
the published literature. Any proposed changes in the consent form or research 
procedures resulting from the report are to be prepared by the study team and 
submitted with the report to the IRB for approval.
9.2 Reporting to St. Jude Institutional Biosafety Committee 
Continuing review reports will be sent to the Institutional Biosafety Committee (IBC) 
on an annual basis using the most current version of the continuing review form 
found on the IBC website. The safety reports, sent to the IRB for both the donors and 
recipients, will be simultaneously forwarded to the IBC. Therefore, reporting for 
safety events to this committee will be according to the same timelines as reporting to 
the IRB.  This includes notification of achievement of MTD (if/when applicable). As 
per the direction of the IBC, only those protocol revisions and amendments directly 
related to the CliniMACS processing and related reagent(s) will require review and 
consideration by the IBC.  Other revisions/amendments will be noted in the IBC 
continuing review report.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
9.3 Reporting to FDA (21CFR§312.32 Safety reports)
The FDA will be notified in writing (IDE safety report) of any serious and 
unexpected AE associated with an investigational treatment or device; or 
any results from laboratory animal tests that suggest a significant risk for human 
subjects including reports of mutagenicity, teratogenicity, or carcinogenicity.
Each notification to the FDA should be made as soon as possible and no later than 15 
calendar days after the sponsor’s initial receipt of the information. The FDA may 
require additional data to be submitted.  In each written IND safety report, the 
sponsor shall identify all safety reports previously filed with the IND concerning a 
similar adverse experience, and shall analyze the significance of the adverse 
experience in light of the previous, similar reports where applicable.
The sponsor shall notify the FDA by telephone or by facsimile transmission of any 
death that occurs within 30 days after infusion of the SJCAR19 product; notification 
will occur as soon as possible, but no later than 7 calendar days after the sponsor’s 
initial receipt of the information. Any grade III-IV infusion reactions will be reported 
as soon as possible, but every effort should be made to assure reporting is no more 
than within 7 business days of the event. In addition to all suspected unexpected 
serious adverse reactions, Grade 4 CRS and neurologic toxicities will be reported to 
the FDA in an expedited fashion. Follow-up information to a safety report must be 
submitted as soon as the relevant information is available.
If the results of further investigation show an AE that was not initially determined to 
be reportable should later be deemed reportable, the sponsor shall inform the FDA of 
the event in a written safety report as soon as possible, but no later than 15 calendar 
days after the determination is made. Results of the investigation of other safety 
information shall be submitted, as appropriate, in an information amendment or 
annual report.  Continuing review reports, which will include the up-to-date clinical 
and safety data, will be submitted to the FDA at least annually.
9.4 Reporting to St. Jude Office of Regulatory Affairs
Copies of all correspondence to the St. Jude IRB, including SAE reports are provided 
to the St. Jude Regulatory Affairs Office. All FDA related correspondence and 
reporting will be conducted through the Regulatory Affairs Office. Adverse event 
reporting and annual reporting will be in accord with the FDA Title 21 CFR312.32 
and Title 21 CFR312.33, respectively. The Regulatory Affairs Office can be reached 
at 901-595-2347 (secondary contact: St. Jude Vice President of Clinical Trials 
Administration 901-595-2876).
9.5 Continuing Review Reports
Continuing review reports of protocol progress and summaries of adverse events will 
be filed with the St. Jude IRB and IBC at least annually. Continuing review reports to 
all regulatory authorities will be structured in a manner so that any infusion toxicities 
or stem cell product related variances will be reported in separate listings from all 
other required elements.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
9.6 Reporting to the Center for International Blood and Marrow Transplant Research
The Transplant Program at St. Jude is required by the federal government to report 
transplant information to the Center for International Blood and Marrow Transplant 
Research (CIBMTR). The CIBMTR is a research partnership of the International 
Bone Marrow Transplant Registry, the National Marrow Donor Program (NMDP), 
and the Foundation for the Accreditation of Cellular Therapy (FACT).  This 
organization is responsible for the collection and maintenance of a standardized data 
warehouse registry of autologous and all allogeneic (related and unrelated donor) 
transplants and cellular infusions performed in the United States.
The Office of General Counsel, U.S. Department of Health and Human Services, had 
deemed the CIBMTR not a covered entity under the Privacy Rule (45 CFR 164.512), 
45 CFR Parts 160 and 164, and the Health Insurance Portability and Accountability 
Act (HIPPA) of 1996.  For this reason, the submission and disclosure of certain 
protected health information (PHI), including that required for CIBMTR, is allowable 
without the individual’s authorization (i.e. consent is waived) when such disclosure is 
made to public health authorities authorized by law for the purpose of preventing or 
controlling disease, injury, or disability.
Data resulting from this procedure may be sent for general registry purposes to 
comply with the federal government requirements.  This information is submitted 
using a unique participant identification number.  The information submitted is less 
extensive than recipients of other donor products.  For this reason, variables 
submitted may include but are not limited to the recipient’s date of birth, country/state 
of current residence, diagnosis, basic lympho-hematopoietic reconstitution post-HCT 
disease status, and basic AEs, survival status, date/cause of death.
10.0 DATA COLLECTION, STUDY MONITORING, AND CONFIDENTIALITY
10.1Data Collection and Submission
The Clinical Research Associates (CRAs) and CRA-RNs, within the Department of 
BMTCT will assure protocol compliance, and conduct all clinical and safety data 
collection. Data will be entered into the St. Jude institutional database at the time it is 
obtained from the electronic health record. The PI and/or designee will be responsible 
for the review of data for accuracy and completeness. The PI and/or designee will 
review the study data at least monthly.
10.2Study Monitoring
This protocol will be monitored for safety and data as per the St. Jude Data and Safety 
Monitoring Plan for Clinical Trials approved by the NCI in 2010. The study team will 
meet at appropriate intervals to review case histories and data quality summaries on all 
participants.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
The St. Jude Clinical Trials Office (CTO) Eligibility Coordinators will verify 100% of 
the informed consent documentation on all participants and verify 100% of 
participant’s eligibility status within 5 working days of completion of enrollment.  
The St. Jude CTO will track accrual continuously and verify 100% of all data points 
related to the primary and secondary objectives including AEs/SAEs every 6-8 weeks 
to assess overall study conduct, human subjects’ protections, and the accuracy of 
database entries. Essential regulatory documents and all study documents including 
medical records, electronic media, database entries, study worksheets, and case report 
forms will be reviewed for recording and reporting of Adverse Events/Serious Adverse 
Events (SAEs) to include type, grade, attribution, duration, timeliness and 
appropriateness. Study documents are also reviewed for participant status, eligibility, 
the informed consent process, demographics, staging, study objectives, subgroup 
assignment, treatments, evaluations, responses, off-study and off-therapy criteria, and 
for all other specifics as detailed in the protocol. The Clinical Research Monitor will 
generate a formal report which is shared with the Principal Investigator, study team and 
the Internal Monitoring Committee (IMC).  
Monitoring may be conducted more frequently if deemed necessary by the CTO or the 
IMC.  
Continuing reviews by the IRB and CT-SRC will occur at least annually.  In addition, 
SAE reports in iRIS are reviewed in a timely manner by the IRB/OHSP.  
The Regulatory Affairs Office will assist the PI in reporting to the FDA and other 
external oversight agencies, as necessary.
10.3Confidentiality
Unique patient numbers will be used in place of an identifier such as a medical record 
number. This unique patient number will be used to identify any data that is released to 
persons or agencies outside of the study team. No research participant names will be 
recorded on the data collection forms. The list containing the unique patient number 
and the medical record number will be maintained in a password protected file that is 
accessible only to study team members.
10.4 Genomic Data Sharing
Genomic and epigenomic data may be shared through the St. Jude Cloud and the 
Database for Genotypes and Phenotypes (dbGAP) and the Gene Expression Omnibus 
(GEO), which are both run by the NIH, and the Sequence Read Archive (SRA). Prior to 
submitting data, data will be stripped of identifiers such as name, date of birth, medical 
record number, and any other information that could be used to identify participants 
and will be fully de-identified by standards consistent with the Common Rule and 
HIPAA. The genotype data will be made publicly available no later than six months 
after completion of sequencing and analysis for all patients on the study, or the date of 
initial publication, whichever comes first.
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
11 STATISTICAL CONSIDERATIONS 
11.1 Overview of Statistical Design and Analysis 
Once a patient is eligible/consented to proceed with treatment with SJCAR19, there 
are two different phases of assessing whether SJCAR19 is safe and effective. The 
first phase of the study is to determine the maximum tolerated dose (MTD). The 
statistical design for this phase is a traditional 3 + 3 Phase I design. The second 
phase of the study will evaluate, using a Simon’s two-stage minimax design, 
evidence that SJCAR19 would be expected to result in complete response (CR) rates 
in an acceptable proportion of treated patients with MTD at enrollment, as well as 
further inform on the safety of this therapy. The statistical design for the Phase II 
study is an expansion cohort at the MTD determined in the Phase I portion of the 
study. Those treated at the MTD in the Phase I study will be evaluated for efficacy 
as part of the Phase II study. In both the Phase I and II portions of the study, the 
primary objectives evaluation period is 4 weeks after initial infusion with SJCAR19. 
Long-term follow-up will occur for 15 years as per FDA guidance. Follow-up will 
occur on protocol for 1 year after the last SJCAR19 infusion. After one year, patients 
will be approached and consented to our existing long-term follow-up institutional 
protocol. If a patient does not enroll on this study, they will continue to be monitored 
on-study (SJCAR19) yearly, for up to 15 years post-infusion, per FDA guidance.
Only patients, who are enrolled on the treatment portion of the protocol (Phase I or 
Phase II [1st infusion only]), will be replaced for the following reasons:
Lost for follow-up within the first 4 weeks post-SJCAR19 infusion (only for 
Phase I)
Meet any of the off-study or off-therapy criteria listed below within the first 4 
weeks post-SJCAR19 infusion:
1) Noncompliance with protocol medications/administrations and/or required 
follow-up evaluations. 
2) Positive pregnancy test after enrolling in the protocol, but prior to receiving 
the study infusion.
3) Enrollment onto a therapeutic study or non-protocol treatment plan, or 
receipt of anti-leuekmia therapy that is not specifically defined in this 
protocol, that would render the ongoing study of the SJCAR19 product or its 
toxicities no longer relevant (in the opinion of the study PIs) (only for Phase 
I).
4) Receipt of any therapy during the initial 4 week evaluation period that could 
interfere with the SJCAR19 product in vivo (ex- chemotherapy, systemic 
steroids), except if that therapy is for the treatment of toxicity that is felt to 
be due to the SJCAR19 therapy (only for Phase I).
5) Withdrawal from protocol.
6) If patient eligible and consented to a portion of the protocol, but then is 
found to be ineligible for subsequent portions of the protocol. 
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
7) Development of a significant change in health status at any point in therapy, 
which in the judgment of the clinical PI, would render continuation in the 
study medically unsafe or not in the participant’s best interest. 
Death due to progressive disease within the first 4 weeks post-SJCAR19 infusion 
(only for Phase I)
Do not receive all of protocol mandated therapy such as:
o
If the patient is unable to receive the protocol defined lymphodepleting 
chemotherapy regimen of fludarabine/cyclophosphamide. They may still 
receive the SJCAR19 infusion, after no chemotherapy or an alternative 
chemotherapy regimen. These patients will be followed per protocol, but 
will be replaced. 
With this study plan, the minimum number of patients (whom received protocol 
defined dosing of SJCAR19 and are evaluable at the 4 week time point) needed for 
the Phase I portion of the study would be 9: 3 on dose level 1 and 6 on dose level -1. 
The maximum number of patients (whom received protocol defined dosing of 
SJCAR19 and are evaluable at the 4 week time point) for Phase I would be 12: 6 
patients on each dose level 1-2. The Phase II expansion cohort will include 12 
additional patients (whom received protocol defined dosing of SJCAR19 and are 
evaluable at the 4 week time point) treated at the MTD determined in the Phase I trial. 
So the total number of patients for the study would be minimum of 21 and maximum 
of 
24. 
Because 
the 
patients 
who 
are 
unable 
to 
receive 
the 
fludarabine/cyclophosphamide lymphodepleting regimen or die due to progressive 
disease will be replaced, we will continue to enroll patients on the study to ensure we 
will have the sufficient number of evaluable patients to assess the primary safety and 
efficacy endpoints. 
Based on our St. Jude protocol NKHEM, the total 24 patients were enrolled on the 
study in five years. With an estimated accrual rate of about 6 participants per year, the 
study is expected to last for about 5-6 years. 
11.2  Dose Limiting Toxicity
A dose limiting toxicity is defined as any toxicity that is considered to be at least 
possibly related to SJCAR19, which is irreversible or life-threatening. 
DLTs will be monitored for 4 weeks post-infusion of SJCAR19, in both the phase I 
and II portions of the study. DLTs to be monitored are shown in Table 5. All 
toxicities, with the exception of cytokine release syndrome (CRS) and neurotoxicity, 
will be determined and graded using the NIH/NCI Common Terminology Criteria for 
Adverse Events (CTCAE v5.0). Abnormal metabolic values will be captured but not 
considered a DLT unless they meet DLT grading limits and the criteria of SAE or are 
deemed as clinically significant per the judgment of the PI. CRS and neurotoxicity 
will be assessed and graded using the ASTCT consensus grading statement for CRS 
and Neurotoxicity58 (Appendices G and H).  Any toxicity that is felt to be resulting 
from CRS or neurotoxicity will be attributed to CRS or neurotoxicity (ex. fever, 
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
oxygen requirement, hypotension, aphasia, confusion, renal insufficiency, 
transaminases57, 58, 62), and not be considered a DLT unless they meet DLT grading 
limits and the criteria of SAE or are deemed as clinically significant per the judgment 
of the PI.
In both the Phase I and II portions of the study, in the event that a DLT is observed, 
the treatment phase of the study will be paused and the DLT will be discussed with 
the study team and the appropriate regulatory committees and agencies including the 
FDA. Based on this review, the study may resume as written, or with modifications.  
Table 5: Dose-Limiting Toxicities 
Treatment-related death (Grade 5)
Grade 4 hematologic toxicity that fails to return to Grade 3 or baseline (whichever is more 
severe) within 4 weeks, except for lymphopenia 
Grade 3 to 4 allergic reaction to SJCAR19 infusion
Grade 3 to 4 treatment-emergent autoimmune toxicity 
Grade 3 CRS or neurotoxicity (protocol defined) that fails to resolve to ≤ Grade 2 within 7 
days of onset#
Grade 4 CRS or neurotoxicity (protocol defined)  that fails to resolve to ≤ Grade 3 within 72 
hours of onset#
In addition to those criteria listed above: 
A dose limiting toxicity is defined as any non-hematologic toxicity* that is considered to be 
at least possibly related to the SJCAR19 product, which is irreversible** or life-
threatening***, and is not pre-existing, due to underlying malignancy and/or associated with 
CRS/Neurotoxicity.
*graded using CTCAE v5.0, with exception of CRS/Neurotoxicity (protocol defined). 
Abnormal metabolic values will be captured but not considered DLTs unless they meet the 
criteria of SAE or deemed as clinically significant per the judgment of the PI.
**A toxicity will be considered irreversible if it does not resolve to ≤ Grade 2 or baseline 
(whichever is more severe) by day 28 post-infusion of the SJCAR19 product.
***A toxicity will be considered life-threatening if it places the participant at immediate risk 
of death from the event as it occurred, per the judgement of the PI.
#The following Grade 3 events, with or without association with CRS and/or Neurotoxicity, 
will be considered DLTs if they fail to resolve to ≤ Grade 2 or baseline (whichever is more 
severe) within 72 hours of onset
-
Nervous System disorders:
o
Amnesia
o
Aphonia
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
IRB APPROVAL DATE: 10/25/2022

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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
11.3
 Dose Escalation
A cohort of 3 participants is treated at a particular dose level and if 0/3 participants 
experience a dose-limiting toxicity (DLT) as defined in Table 5 in the toxicity 
evaluation period, then the next cohort of 3 is treated at the next higher dose level.  If 
1/3 experiences DLT then an additional cohort of 3 participants is treated at the same 
dose level. If 1/6 participants experiences DLT at this level then the next cohort of 3 
participants will be treated at the higher dose level.  If 2+/6 (or 2+/3 in the initial 
cohort) experience DLT, then that would mean that the MTD has been exceeded.  In 
such a situation, the previous dose level is declared to be the MTD if 6 participants 
have already been treated at that dose level, otherwise an additional cohort of 3 
participants is treated at that dose level.  The MTD is then defined as the highest dose 
level at which 6 participants have been treated with no more than 1 instance of DLT. 
Finally, if there is no DLT on the last dose level 2, we will claim MTD not reached. 
If there is 2 or more DLT in the dose level 1, then dose level 0 will be evaluated. The 
o
Arachnoiditis
o
Brachial plexopathy
o
Central Nervous System Necrosis
o
Cerebrospinal fluid leakage
o
Depressed level of consciousness
o
Intracranial hemorrhage
o
Myelitis
o
Pyramidal tract syndrome
o
Radiculitis
o
Recurrent laryngeal nerve palsy
o
Seizure (multiple seizures)
o
Somnolence
o
Stroke
o
Transient ischemic attack
-
Cardiac disorders:
o
Aortic Valve disease
o
Atrial fibrillation
o
Atrial flutter
o
AV block complete
o
Chest pain
o
Conduction disorder
o
Mitral valve disease
o
Mobitz type II and type I
o
Myocardial infarction
o
Myocarditis
o
Pericarditis
o
Pulmonary valve disease
o
Restrictive cardiomyopathy
o
Sick sinus syndrome
o
Sinus bradycardia
o
Tricuspid valve disease
o
Ventricular arrhythmia
o
Congenital, familial and genetic disorders- other, specify
St. Jude Children's Research Hospital
IRB NUMBER: Pro00007661
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
dose escalation schema and toxicities observed and the actions to be taken are listed 
below (Table 6).
In the Phase I study, patients will be enrolled on a particular treatment dose level on 
a staggering basis. For each dose level being evaluated, there will be a 4 week period 
between SJCAR19 infusions for patients 1 and 2. This time period should allow for 
sufficient length of time for the monitoring of adverse events, as the most common 
anticipated AE is CRS and it has been reported that the median time to onset of CRS 
is 3 – 4 days.  However, at no time the number of participants experienced DLT 
within 4 weeks plus the number of participants receiving the SJCAR19 infusion and 
not yet passing 4 weeks’ evaluation will exceed two (2). Additionally, the first three 
(3) patients treated on study must be aged ≥ 16 years old.
Table 6: The toxicities observed and the actions to be taken
# Patients
# DLTs
Action
3
0
escalate to next level
3
1
enroll 3 more at this level
6
1
escalate to next level
3-6
2
declare MTD exceeded and treat 3 more at the previous 
dose level if only 3 were treated; or the previous dose 
is MTD if 6 were treated at the previous dose
11.4 Efficacy and Stopping Rules
The complete response rate for standard therapy is 40%. The goal of our study is to 
use SJCAR19 to improve the treatment outcome at a complete response (CR) rate 
of ≥70%.  We do not anticipate censoring within 4 weeks after SJCAR19 infusion 
and we can approximate the rate of CR within 4 weeks after SJCAR19 infusion 
using a Binomial distribution. (However, within 4 weeks, patients lost for follow 
up, who die due to treatment related toxicity, enroll onto a therapeutic study or non-
protocol treatment plan, or receipt of anti-leuekmia therapy that is not specifically 
defined in this protocol, that would render the ongoing study of the SJCAR19 
product or its toxicities no longer relevant (in the opinion of the study PIs),  or 
receive any therapy that could interfere with the SJCAR19 product in vivo (ex- 
chemotherapy, systemic steroids), except if that therapy is for the treatment of 
toxicity that is felt to be due to the SJCAR19 therapy will be counted as a failure to 
complete response in order to keep the validity of Binomial distribution 
approximation). Therefore, in this study, we propose to test the null hypothesis H0: 
P≤0.40 versus H1: P>0.40, where P is the proportion of research participants with 
complete response within 4 weeks after the SJCAR19 infusion. With type I error of 
5% and type II error of 20%, Simon’s two stage minimax design powered at 
alternative successful complete response rate P1=0.70 requires 12 evaluable patients 
at the first stage and 18 evaluable patients in total.87 The stopping rules are provided 
in Table 7, with the understanding that stopping the trial early would be suggestive 
of the proposed new treatment strategy not being an effective treatment option for 
this group of patients. 
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
The interpretation is that if we observe ≤ 6 participants with complete response 
within 4 weeks after SJCAR19 infusion in 12 participants treated at the MTD (6 
treated at MTD in Phase I, 6 enrolled at MTD on Phase II), then we would stop the 
trial for lack of efficacy and will not enroll another 6 patients. The probability of 
stopping the trial early if the true CR rate is 0.4 or less, is 0.84. However, if we 
observe ≥ 7 patients with complete response within 4 weeks after SJCAR19 
infusion in the initial 12 participants treated at the MTD, then 6 more patients will 
be enrolled on the Phase II portion of the study. 
After the study is finished, the function twostage.inference in clinfun R package 
that accounts for the two-stage design will be used to calculate the confidence 
interval. 
Table 7: Stopping rules for lack of efficacy based on the Simon’s 2-stage 
minimax design (unacceptable low rate of complete response within 4 weeks 
after the T cell infusion) 
Accept H0 if the number of research participants with complete response
P0
P1
(≤ r1/n1 )
(≤ r/n )
EN(P0)
PET(P0)
0.40
0.70
6/12
10/18
12.9
0.84
Note: r1 and r denote the number of patients with complete response within one month 
after the completion of therapy; EN(P0) denotes the expected sample size under P0; 
PET(P0) denotes the probability of early termination at stage I under P0. 
Additionally, we will pause treatment study enrollment, pending further 
investigation, for any Grade 5 AE other than that related to progressive disease, or 
if 2 patients experience a Grade 4 AE related to vital organs (that is not included in 
the CRS/neurotoxicity grading system), that occurs within 4 weeks of infusion of 
SJCAR19.  
Data from any reinfusions may be included in safety, efficacy and exploratory 
analysis, but will not be included in primary objective analysis. This data will be 
collected as a unique infusion, but not as a unique patient (i.e. reinfusion does not 
count towards enrollment goals).
11.5 Analysis for Exploratory Objectives 
Responsible investigators: All investigators will be responsible for all exploratory 
objectives except 11.5.10-11.5.11. 
11.5.1 To describe the feasibility of manufacturing SJCAR19 for pediatric and 
young adult patients ≤ 21 years of age, with relapsed or refractory CD19+ 
ALL, and explore possible factors contributing to manufacturing failure. 
The number of patients who do not receive the protocol defined dose of 
SJCAR19 will be reported. To explore possible factors contributing to 
manufacturing failure, we will compare factors between patients who do 
and who don’t receive the protocol defined dose of SJCAR19. Depending 
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on the number, summary statistics including the number and frequency for 
categorical variables and mean, SD, median and range for continuous 
variables will be reported. They will be compared using Fisher’s exact test 
for categorical variables and two-sample t-test or Wilcoxon rank sum test 
depending on the normality of the data tested with Shapiro-wilk test for 
continuous variable, respectively. Generalized linear regression model 
may also be used to explore possible factors contributing to the 
manufacturing failure.
Time frame: The final analyses will begin 1 day after the last patient is 
enrolled and treated.
11.5.2 To evaluate the relapse-free survival of patients with minimal residual 
disease at the time of treatment with SJCAR19.
The Kaplan-Meier estimates of relapse-free survival of patients with 
minimal residual disease along with their standard errors will be calculated 
using the SAS macro (bmacro251-Excel2007\kme) available in the 
Department of Biostatistics at St. Jude, where EFS = min (date of last 
follow-up, date of relapse) – date of treatment, and all participants 
surviving at the time of analysis without events will be censored. The 
analysis for this objective will be performed when the last evaluable 
participant has been followed for one-year post treatment. Because 
patients with minimal residual disease dying from toxicity will be 
competing risk event for relapse, CI analyses will also be conducted.
Time frame: The final analyses will begin 1 year after the last patient is 
enrolled and treated.
11.5.3 To study the expansion, persistence and phenotype of SJCAR19.
These samples will be collected over a year. Variables will be expansion 
(number of detectable SJCAR19 cells), persistence (presence of detectable 
SJCAR19 cells) and phenotype (cell surface markers of SJCAR19 cells). 
At each time point, summary statistics including mean, SD, median and 
range will be reported. Box-cox plot will also be used to visually look at 
the trend of the expansion, persistence and phenotype of SJCAR19 over 
time. The change over time for the expansion, persistence and phenotype 
of SJCAR19 will be estimated using linear mixed model with assessment 
times as a covariate. We will also explore if there is difference between 
patients in phase I and those on MTD in phase II by including group as a 
covariate in the model.
Time frame: The final analyses will begin 1 year after the last patient is 
enrolled and treated.
11.5.4 To characterize the cytokine profile in the peripheral blood and CSF after 
treatment with SJCAR19.
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These samples will be collected over a year. Variables will be levels of 
specific cytokines. The analyses methods will be similar to those for 
objective 11.5.6.
Time frame: The final analyses will begin 1 year after the last patient is 
enrolled and treated.
11.5.5 To explore the use of next-generation sequencing (NGS) for the 
monitoring of disease status post-treatment with SJCAR19 compared to 
minimal residual disease detection via flow cytometry.
Since NGS is more sensitive to monitor disease post treatment with 
SJCAR19, the sensitivity and specificity comparison between NGS and 
the flow cytometry will be performed for patients for whom both assays 
are performed. The agreement in percent of leukemia cells using NGS and 
flow cytometry will also be evaluated using intraclass correlation 
coefficient. 
Time frame: The final analyses will begin 1 year after the last patient is 
enrolled and treated.
11.5.6  To determine the immune reconstitution post SJCAR19 treatment, and 
clonal structure and endogenous repertoire of CAR T cells during in vitro 
and in vivo expansion.
The standard protocols for repertoire analysis and quantitative assessment 
of repertoire diversity and specificity will be used on longitudinal samples 
from in vitro and in vivo expanded CAR T cell populations. Outcomes 
will include the diversity (assessing both richness and evenness) of CAR T 
cell and unmodified immune cell populations over time and the 
identification of receptor families from known specificities (e.g. common 
infections such as influenza, herpesvirus etc) that preferentially associate 
with expanded clones. VIS analysis will also be performed.
Time frame: The final analyses will begin 1 year after the last patient is 
enrolled and treated.
11.5.7  To assess whether CAR T cells acquire functional versus exhaustion-
associated epigenetic programs during in vitro and in vivo expansion.
Loci-specific analyses can be performed with a few hundred cells, and we 
have currently optimized conditions to perform whole-genome bisulfite 
sequencing on ~20,000 cells. Loci-specific analyses may include regions 
of the genome that code for effector molecule, inhibitory receptor, and 
homing molecule loci (e.g. granzyme b, perforin, PD-1, CTLA4 Lag3, 
2B4, and CD62L). We will perform loci-specific analyses with samples 
that yield <10,000 PD-1+ T cells.  Whole genome bisulfite sequencing 
may be performed on samples that yield >10,000 PD-1+ T cells.
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Time frame: The final analyses will begin 1 year after the last patient is 
enrolled and treated.
11.5.8 To longitudinally assess and quantify the symptoms, associated distress, 
and functional impairment experienced by patients enrolled on this Phase 
I/II clinical trial. 
The scores of each PRO-CTCAE attribute (frequency, severity, and/or 
interference) at all time points will be summarized by descriptive statistics 
separately for the patient and parent proxy groups, e.g., mean, SD, median 
and range, proportion. If an adequate sample size is available in each 
group, the changes of scores at each pair of adjacent time points will be 
tested with Wilcoxon signed-rank test.
Time frame: The final analyses will begin 1 year after the last patient is 
enrolled and treated.
11.5.9 To longitudinally assess and quantify numerous metrics of quality of life 
and well-being for patients enrolled on this Phase I/II trial and their 
primary caretakers.
11.5.9.1
The total and subscale scores of PedsQL V. 4 and PedsQL – 
Cancer V. 3 at all time points will be summarized by descriptive 
statistics separately for the patient and parent proxy group. The 
scores measuring the quality of life and well-being for the 
caretaker at all time points will also be summarized by descriptive 
statistics. The correlations among the scores will be estimated by 
Pearson correlation coefficient or Spearman's rank correlation 
coefficient and tested by Fisher transformation. The scores 
between the groups, e.g., high and low burden, will be tested with 
Wilcoxon rank-sum test. 
The changes of scores at each pair of adjacent time points will be 
tested with Wilcoxon signed-rank test. If an adequate sample size 
is available, the patterns of the longitudinal change will be 
determined and linear mixed effects or GEE model will be fitted to 
the scores to validate the longitudinal trends and the relations 
among the scores. 
Time frame: The final analyses will begin 1 year after the last 
patient is enrolled and treated.
11.5.9.2 
Semi-structured interviews will be recorded and manually 
transcribed into MaxQDA. Analysis of this data will be performed 
by trained members of the quality of life division using an applied 
thematic analysis approach, which is an iterative process of 
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identifying themes or units of meaning observed in the data. 
Members of the quality of life division with extensive experience 
in thematic analysis will jointly develop themes for all interviews, 
which they will then refine into codes with well-developed 
definitions. Once code definitions have been finalized, two 
additional individuals will serve as independent raters to evaluate 
the transcripts. These individuals will complete study specific 
training in content analysis and use of the codes. After completing 
training, the two independent raters will analyze the interviews. 
Kappa coefficients will be calculated to measure the inter-coder 
reliability between each of the raters.
Time frame: Qualitative analysis will be ongoing, with interviews 
being transcribed and analyzed as they are completed.
11.5.10 To characterize incidence and mechanisms of resistance and/or relapse 
post therapy with SJCAR19.
The estimate of cumulative incidence of relapse will be determined using 
Kalbfleisch-Prentice method. Death without relapse is the competing risk 
event. The Kaplan-Meier estimates of OS and EFS along with their 
standard errors will be calculated using the SAS macro (bmacro251-
Excel2007\kme) available in the Department of Biostatistics at St. Jude, 
where OS = min (date of last follow-up, date of death) – date of infusion 
and all participants surviving at the time of analysis without events will be 
censored, and EFS = min (date of last follow-up, date of relapse, date of 
death due to any cause) – date of infusion, and all participants surviving at 
the time of analysis without events will be censored. The final analysis for 
this objective will be performed when the last evaluable participant has 
been followed for one-year post-CAR T-cell infusion.
12.0 OBTAINING INFORMED CONSENT
12.1
Informed Consent
This protocol contains a 3-part informed consent process. Patients that meet 
eligibility for autologous apheresis will be consented to undergo collection of 
autologous peripheral blood mononuclear cells (PBMC) via apheresis. 
Alternatively, patients whom have previously undergone autologous apheresis 
may be considered for enrollment on the manufacturing portion of the study if it is 
determined that their previously collected product is appropriate for use in 
manufacturing; these patients would therefore not need to be consented using the 
SJCAR19 apheresis consent. When the patient meets eligibility criteria to begin 
manufacturing of SJCAR19, they will be consented to proceed with 
manufacturing of the SJCAR19 product using their collected autologous cells. At 
this time, patients/guardians will be provided with an FYI consent for the 
treatment portion of the study. Lastly, when a SJCAR19 product has 
manufactured for an individual patient and they meet eligibility criteria to receive 
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therapy with SJCAR19, they will be consented to proceed with the treatment 
portion of the study. 
12.2
Informed Consent Prior to Research Interventions
The PI or physician sub-investigator will conduct the signature authorization 
portion of the consent process. Authorization for the recipient procedure should 
be conducted in the presence of an independent witness, such as a nurse from the 
St. Jude Department of Nursing or the St. Jude Institutional Review Board 
Ombudsperson/Patient Advocate, as applicable and available to serve as a 
witness.
12.3
Consent at Age of Majority 
The age of majority in the state of Tennessee is 18 years old. Research 
participants must be consented at the next clinic visit after the 18th birthday. If an 
affiliate is located in a country or state where a different age of majority applies, 
the location must consent the participants according to their local laws.
12.4
Consent When English is Not the Primary Language
When English is not the patient, parent, or legally authorized representative’s 
primary language, the Social Work department will determine the need for an 
interpreter.  This information documented in the participant’s medical record.  
Either a certified interpreter or the telephone interpreter’s service will be used to 
translate the consent information.  The process for obtaining an interpreter and for 
the appropriate use of an interpreter is outlined on the Interpreter Services, OHSP, 
and CTO websites. 
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St. Jude Children's Research Hospital
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antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and 
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Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M et al. 4-1BB 
costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric 
antigen receptors. Nature medicine 2015; 21(6): 581-590. doi: 10.1038/nm.3838
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virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific 
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Youngblood B, Noto A, Porichis F, Akondy RS, Ndhlovu ZM, Austin JW et al. Cutting 
edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 
expression in virus-specific CD8 T cells. Journal of immunology 2013; 191(2): 540-544. 
doi: 10.4049/jimmunol.1203161
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transcriptional signatures and epigenetics. Immunology 2013; 139(3): 277-284. doi: 
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Cukalac T, Kan WT, Dash P, Guan J, Quinn KM, Gras S et al. Paired TCRalphabeta 
analysis of virus-specific CD8(+) T cells exposes diversity in a previously defined 
'narrow' repertoire. Immunology and cell biology 2015; 93(9): 804-814. doi: 
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Wang GC, Dash P, McCullers JA, Doherty PC, Thomas PG. T cell receptor alphabeta 
diversity inversely correlates with pathogen-specific antibody levels in human 
cytomegalovirus infection. Science translational medicine 2012; 4(128): 128ra142. doi: 
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Gerlach C, Rohr JC, Perie L, van Rooij N, van Heijst JW, Velds A et al. Heterogeneous 
differentiation patterns of individual CD8+ T cells. Science 2013; 340(6132): 635-639. 
doi: 10.1126/science.1235487
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Thomas PG, Handel A, Doherty PC, La Gruta NL. Ecological analysis of antigen-specific 
CTL repertoires defines the relationship between naive and immune T-cell populations. 
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Basch E, Jia X, Heller G, Barz A, Sit L, Fruscione M et al. Adverse symptom event 
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National Cancer Institute 2009; 101(23): 1624-1632. doi: 10.1093/jnci/djp386
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Wolfe J, Orellana L, Cook EF, Ullrich C, Kang T, Geyer JR et al. Improving the care of 
children with advanced cancer by using an electronic patient-reported feedback 
intervention: results from the PediQUEST randomized controlled trial. Journal of clinical 
oncology : official journal of the American Society of Clinical Oncology 2014; 32(11): 
1119-1126. doi: 10.1200/JCO.2013.51.5981
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80.
Wolfe J, Orellana L, Ullrich C, Cook EF, Kang TI, Rosenberg A et al. Symptoms and 
Distress in Children With Advanced Cancer: Prospective Patient-Reported Outcomes 
From the PediQUEST Study. Journal of clinical oncology : official journal of the 
American Society of Clinical Oncology 2015; 33(17): 1928-1935. doi: 
10.1200/JCO.2014.59.1222
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Hibbard JH, Greene J. What the evidence shows about patient activation: better health 
outcomes and care experiences; fewer data on costs. Health Aff (Millwood) 2013; 32(2): 
207-214. doi: 10.1377/hlthaff.2012.1061
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Weitzner MA, Jacobsen PB, Wagner H, Jr., Friedland J, Cox C. The Caregiver Quality of 
Life Index-Cancer (CQOLC) scale: development and validation of an instrument to 
measure quality of life of the family caregiver of patients with cancer. Qual Life Res 
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being in people with cancer: the functional assessment of chronic illness therapy--
Spiritual Well-being Scale (FACIT-Sp). Ann Behav Med 2002; 24(1): 49-58. 
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Depression Scale. An updated literature review. Journal of psychosomatic research 2002; 
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DeCamp LR, Leifheit K, Shah H, Valenzuela-Araujo D, Sloand E, Polk S et al. Cross-
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Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989; 
10(1): 1-10. 
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APPENDIX A: Karnofsky and Lansky Performance Status 
KARNOFSKY PERFORMANCE STATUS SCALE
≥ 16 YEARS OLD
Score
General Description
100
Normal. No complaints. No evidence of disease.
90
Able to carry on normal activity. Minor signs or symptoms of disease.
80
Normal activity with effort. Some signs or symptoms of disease.
70
Care of self.  Unable to carry out normal activity or to do active work.
60
Requires occasional assistance, but is able to care for most of his needs.
50
Requires considerable assistance and frequent medical care.
40
Disabled.  Requires special care and assistance.
30
Severely disabled. Hospitalization is indicated although death is not imminent.
20
Hospitalization necessary, very sick, active support treatment necessary.
10
Moribund. Fatal processes progressing rapidly.
0
Dead.
LANSKY PERFORMANCE STATUS SCALE
< 16 YEARS OLD
Score 
General Description
100
 Fully active, normal
90 
Minor restrictions in physically strenuous activity
80
Active, but tires more quickly
70
Both greater restriction of and less time spent in play activity
60
Up and around, but minimal active play; keeps busy with quieter activities
50
Gets dressed but lies around much of the day, no active play but able to participate in 
all quiet play and activities
40
Mostly in bed; participates in quiet activities
30
In bed; needs assistance even for quiet play
20
Often sleeping; play entirely limited to very passive activities
10
No play; does not get out of bed
0
Unresponsive
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Protocol document date: 10/17/2022
APPENDIX B: Steroid Equivalent Dose Reference Chart
Standard Equivalent Dose
Protocol Equivalent Dose
Cortisone
25
3.125 mg/kg/day
Dexamethasone
0.75
0.09375 mg/kg/day
Hydrocortisone
20
2.5 mg/kg/day
Methylprednisolone
4
0.5 mg/kg/day
Prednisolone
5
0.625 mg/kg/day
Prednisone
5
0.625 mg/kg/day
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Protocol document date: 10/17/2022
APPENDIX C: Study Overview
Meets inclusion criteria 
for Autologous Apheresis? 
No
Yes
Not eligible for 
enrollment/apheresis at this time 
Patient consented for autologous apheresis; timing of 
apheresis to be determined by patient status in 
discussion with PI and primary team
Meets inclusion criteria for 
Manufacturing SJCAR19?
Apheresis product cryopreserved 
Patient consented for 
Manufacturing of SJCAR19, 
and the manufacturing process 
will begin (see Appendix D)
Yes
Yes
No
No
Does the generated product meet 
release and dose criteria?
Begin protocol treatment 
Patient taken off study 
Does the patient meet 
eligibility criteria for 
Treatment with 
SJCAR19?
No
Yes
Patient consented for 
Treatment with SJCAR19
Meets inclusion criteria for 
Manufacturing SJCAR19 at 
later time point?
Yes
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Protocol document date: 10/17/2022
APPENDIX D: Overview of SJCAR19 Manufacturing Procedure
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SJCAR19 - 68
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Protocol document date: 10/17/2022
APPENDIX E:  Recommended Treatment Evaluations Study Calendar
Study Evaluation Target Windows
+ 4 days
+ 15 days
+ 28 days
Study
Wk
-1
Wk
0
Wk
1
Wk
2
Wk
3
Wk
4
Wk
8
Mth
3
Mth
6
Mth
9
Mth 
12
Cy + Flu^
X
SJCAR19  Infusion
X
Hx
X*
X**
X
X
X
X
X
X
X
X
X
PE
X*
X**
X
X
X
X
X
Performance Status
X*
X**
X
X
X
X
X
CBC with diff
X*
X**
X
X
X
X
X
X
X
X
X
Lytes, BUN, Cr
X*
X**
X
X
X
X
X
AST/ALT, Bili, Alb
X*
X**
X
X
X
X
X
CRP, Ferrtin
X*
X**
X
X
X
X
X
Lymphocyte Subset Panel
X*
X
X
X
X
X
X
Quantitative Immunoglobulins
X*
X
X
X
X
X
X
Pregnancy Test#
X*
RCL Testing 
X*
X
X
X&
HAMA  
X**
X
ECHO
X@
EKG
X@
X**
Peripheral MRD
X%
X**
X
X
BMA
X%
X
X
CSF
X%
X
X†
SJCAR19 Research Labs
Cytokines
X*
X***
X
X
X
X
X
Persistence Studies
X***
X
X
X
X
X
X
X
X
X
Function Studies
X*
X**
X
X
X
X
X
X
X
X
X
Leukemia/ Microenvironmenta
X%
X
For SJCAR19 Research Labs, additional samples may be sent if the patient has concern for disease relapse/progression, or an acute clinical change that is felt to 
possibly be related to the SJCAR19 product. Research laboratory testing may also be performed using a leftover clinically indicated sample.
@ 
to be performed within 2 weeks prior to the start of protocol lymphodepleting chemotherapy 
% 
to be performed after any bridging chemotherapy and within 2 weeks prior to start of protocol lymphodepleting chemotherapy 
^
starts day -4, if unable to receive Cy or Flu, select patients may receive alternative regimen in discussion with PI  prior to start of lymphodepleting chemotherapy 
**
post-lymphodepleting chemotherapy (if applicable)/pre T-cell infusion 
***
pre T-cell infusion and 1 to 4 hours post infusion and an optional sample 3-4 days post infusion (optional per discretion of PI/Transplant Attending) 
#
Pregnancy testing is only required in female patients of childbearing potential 
†
only for patients with recent history of CNS disease
& 
If a patient does not enroll on our institutional long-term follow-up protocol, we will continue to monitor RCL testing on-study per FDA guidance 
a
If a patient has circulating peripheral blood blasts at any time while on study, this analysis may also be perfomed on that study sample.

Several laboratory tests can only be processed on weekdays; therefore, if the scheduled evaluation falls on a weekend, or during a holiday period, an adjustment in the 
follow-up visit is expected and would not be noted as a protocol variation. Additionally, in order to accommodate such logistical constraints, evaluation/collection dates of 
all protocol assessments (required and optional research), may be performed within a reasonable window of the intended date following the guidelines provided in the table 
headers. 

After week +4 participants may no longer be receiving treatment at St. Jude Children’s Research Hospital or its affiliates. For this reason, variations in the timing and 
frequency (more or less frequent) of these evaluations, with the exception of the SJCAR19 RCL, and SJCAR19 Research labs, can occur due to the participant’s clinical 
condition and will not be noted as protocol deviations after week +4. 

For any reinfusions, patients will follow this study calendar beginning with week -1
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
APPENDIX F: Criteria for Adverse Event (AE) Evaluation and Reporting 
The St. Jude Department of BMTCT Clinical Research Office standard operating procedure for 
the documenting and reporting of adverse (SOP 10 Documenting and Reporting of Adverse 
Events https://home.stjude.org/bmt/Policies/10.pdf) will provide guidance on the evaluation, 
collection and reporting of adverse events for this clinical trial. The current version of this 
document, as well as ongoing updates, can be located at the following website: 
http://home.stjude.org/bmt/Pages/policies-research.aspx
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Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
 APPENDIX G: Criteria for Cytokine Release Syndrome (CRS) Adverse Event (AE) 
Grading (ASTCT CRS Consensus Grading) #
# Symptoms should be graded individually using the CTCAE grading system, but will collectively be 
attributed/reported as part of the overall CRS grade. Symptoms and signs of CRS occurring after infusion 
of CAR T-cell products may include constitutional symptoms (fever, rigors, headache, malaise, fatigue, 
nausea, vomiting, arthralgia), vascular (hypotension), cardiac (arrhythmia, tachycardia), respiratory 
compromise, renal (rise in creatinine, kidney failure, uremia) and laboratory (including coagulopathy and 
a hemophagocytic lymphohistiocytosis-like syndrome) changes.
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SJCAR19 - 71
Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
APPENDIX H: Criteria for Neurotoxicity Adverse Event (AE) Grading (ASTCT 
Neurotoxicity Consensus Grading) #
# Symptoms should be graded individually using the CTCAE grading system, but will collectively be 
attributed/reported as part of the overall neurologic toxicity grade; symptom examples are not all 
inclusive. examples include: mental status changes, tremor, agitation, aphasia, delirium, dizziness, 
dyskinesia, hallucination and restlessness
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SJCAR19 - 72
Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
Appendix H (continued)
Encephalopathy Assessment Tool for Grading ICANS
ICE: (ages ≥ 12 years old) 
CAPD: (< 12 years old) 
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SJCAR19 - 73
Amendment 6.1, dated 10/17/2022
Protocol document date: 10/17/2022
APPENDIX I: Quality of Life Evaluations Study Calendar
QoL Related Studies Calendar* and Assessment Administration by Age and Time Point
*QOL assessments may be conducted up to an additional 3 times during the first 4 weeks after cellular infusion as needed to capture peak 
symptoms; For any reinfusions, patients will follow this study calendar beginning with week 0
Study
Wk 0
Wk 2
Wk 4
Wk 8
Mth 3
PRO-CTCAE (English/Spanish)
X
X
X
X
X
PedsQL V.4 (English/Spanish)
X
X
X
X
X
PedsQL – Cancer V.3 (English/Spanish)
X
X
X
X
X
Good Day Bad Day Scale (English)
X
X
X
X
X
Qualitative Symptom Assessment (English)
X
X
X
X
X
CQOLC (English/Spanish) 
X
X
X
X
FACIT-Sp-12 (English/Spanish)
X
X
X
X
Hospital Anxiety and Depression Scale (English) 
X
X
X
X
Herth Hope Index (English/Spanish)
X
X
X
X
Modified Parent-Patient Activation Measure (English)
X
X
X
X
Assessment Administration by Age and Time Point
Wk 0
Wk 2
Wk 4
Wk 8
Mth 3
Patients: 
0-4 yrs
Caregiver 
Participation Only
Caregiver 
Participation Only
Caregiver 
Participation Only
Caregiver 
Participation Only
Caregiver 
Participation Only
Patients: 
5-7 yrs
Good/Bad Day*
Qual Symp*
PedsQL
PedsQL-C
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
Good/Bad Day* 
Qual Symp* 
PedsQL
PedsQL-C
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
Patients: 
8-15 yrs
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (P)
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (P)
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (P)
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (P)
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (P)
Patients: 
16-21 yrs
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (A)
Good/Bad Day*
Qual Symp*
PedsQL
PedsQL-C
PRO-CTCAE (A)
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (A)
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (A)
Good/Bad Day*
Qual Symp* 
PedsQL
PedsQL-C
PRO-CTCAE (A)
Caregivers
Good/Bad Day*
Qual Symp* 
PedsQL+
PedsQL-C+
PRO-CTCAE (C)
CQOLC
FACIT-Sp-12
HADS
HHI
mP-PAM*
Good/Bad Day*
Qual Symp* 
PedsQL+
PedsQL-C+
PRO-CTCAE (C)
Good/Bad Day*
Qual Symp* 
PedsQL+
PedsQL-C+
PRO-CTCAE (C)
CQOLC
FACIT-Sp-12
HADS
HHI
mP-PAM*
Good/Bad Day*
Qual Symp* 
PedsQL+
PedsQL-C+
PRO-CTCAE (C)
CQOLC
FACIT-Sp-12
HADS
HHI
mP-PAM*
Good/Bad Day*
Qual Symp* 
PedsQL+
PedsQL-C+
PRO-CTCAE (C)
CQOLC
FACIT-Sp-12
HADS
HHI
mP-PAM*
Good/Bad Day = Good Day Bad Day Scale, Qual Symp = Qualitative Symptoms Assessment, PedsQL = Pediatric Quality of Life Inventory V. 4, 
PedsQL-C = PedsQL Cancer Module V. 3, PRO-CTCAE (P) = PRO-CTCAE Pediatric Form, PRO-CTCAE (A) = PRO-CTCAE Adult Form, 
PRO-CTCAE (C) = PRO-CTCAE Caregiver Proxy Form, CQOLC = Caregiver Quality of Life Index – Cancer, FACIT-Sp-12 = Functional 
Assessment of Chronic Illness Therapy – Spiritual Well-Being Subscale, HADS = Hospital Anxiety and Depression Index, HHI = Herth Hope 
Index, mP-PAM = Modified Patient-Parent Activation Measure
*Not included for Spanish speaking patients and families.
+Used only for caregivers of children aged 2 years and older.
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IRB NUMBER: Pro00007661
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