A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas
A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas
The study will be conducted in compliance with the International Council for Harmonisation
 (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good
 Clinical Practice (GCP) and applicable regulatory requirements.

 This is a randomized, open-label, parallel-group, multi-center trial in adult subjects with
 Relapsed or refractory (R/R) aggressive Non-Hodgkin lymphoma (NHL) to compare safety and
 efficacy between the standard of care (SOC) strategy versus JCAR017 (also known as
 lisocabtagene maraleucel or liso-cel). Subjects will be randomized to either receive SOC (Arm
 A) or to receive JCAR017 (Arm B).

 All subjects randomized to Arm A will receive Standard of care (SOC) salvage therapy (R-DHAP,
 RICE or R-GDP) as per physician's choice before proceeding to High dose chemotherapy (HDCT)
 and Hematopoietic stem cell transplant (HSCT).

 Subjects from Arm A may be allowed to cross over and receive JCAR017 upon confirmation of an
 EFS event.

 Subjects randomized to Arm B will receive Lymphodepleting (LD) chemotherapy followed by
 JCAR017 infusion.
Inclusion Criteria:

 1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed
 consent form (ICF).

 2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

 3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or
 transformed indolent NHL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6
 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]), primary
 mediastinal (thymic) large B-cell lymphoma (PMBCL), T cell/histiocyte-rich large
 B-cell lymphoma (THRBCL) or follicular lymphoma grade 3B. Enough tumor material must
 be available for confirmation by central pathology.

 4. Refractory or relapsed within 12 months from CD20 antibody and anthracycline
 containing first line therapy.

 5. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at
 screening. (Deauville score 4 or 5)

 6. Adequate organ function

 7. Participants must agree to use effective contraception

 Exclusion Criteria:

 1. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).

 2. Subjects planned to undergo allogeneic stem cell transplantation.

 3. Subjects with, primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus)
 positive DLBCL, Burkitt lymphoma or transformation from chronic lymphocytic
 leukemia/small lymphocytic lymphoma (Richter transformation).

 4. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the
 subject has been free of the disease for ≥ 2 years with the exception of the following
 noninvasive malignancies:

 -  Basal cell carcinoma of the skin

 -  Squamous cell carcinoma of the skin

 -  Carcinoma in situ of the cervix

 -  Carcinoma in situ of the breast

 -  Incidental histologic finding of prostate cancer (T1a or T1b using the TNM
 [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is
 curative.

 -  Other completely resected stage 1 solid tumor with low risk for recurrence

 5. Treatment with any prior gene therapy product.

 6. Subjects who have received previous CD19-targeted therapy.

 7. Subjects with active hepatitis B, or active hepatitis C are excluded. Subjects with
 negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are
 permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B
 core antibody with negative viral load are eligible and should be considered for
 prophylactic antiviral therapy. Subjects with a history of or active human
 immunodeficiency virus (HIV) are excluded.

 8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection
 (including tuberculosis) despite appropriate antibiotics or other treatment.

 9. Active autoimmune disease requiring immunosuppressive therapy.

 10. History of any one of the following cardiovascular conditions within the past 6 months
 prior to signing the ICF: Class III or IV heart failure as defined by the New York
 Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction,
 unstable angina, or other clinically significant cardiac disease.

 11. History or presence of clinically relevant central nervous system (CNS) pathology

 12. Pregnant or nursing (lactating) women.