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Clinical Trial 20271

Cancer Type: Immunotherapy
Study Type: Treatment
NCT#: NCT03575351

Phase: Phase III
Prinicipal Investigator: Julio Chavez

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Overview

Study Title

A Global Randomized Multicenter Phase 3 Trial 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 (TRANSFORM)

Summary

This is a randomized, open-label, parallel-group, multi-center trial in adult patients 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). Patients will be randomized to either receive SOC (Arm A) or to receive JCAR017 (Arm B).

Objective

The primary of objective of the study is to compare the efficacy in subjects treated with JCAR017 versus subjects treated according to standard of care (SOC) defined as event-free survival (EFS). The key secondary objectives are to compare the efficacy in subjects treated with JCAR017 versus subjects treated according to SOC defined as complete response rate (CRR), progression-free survival (PFS) and overall survival (OS). The secondary objectives are: -to compare other parameters of efficacy, defined as duration of response (DOR), overall response rate (ORR), PFS on next line of treatment (PFS-2) -to compare efficacy rates (EFS, PFS, OS) at 6, 12, 24, and 36 months after randomization -to compare the safety defined as type and frequency of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities -to compare the safety and efficacy in clinical, histological and molecular subgroups -to compare health-related quality of life (HRQoL) -to compare hospital resource utilization (HRU) -to describe the rate of completion of high dose chemotherapy (HDCT) and hematopoietic stem cell transplant (HSCT) -to assess the response 3 months after-HSCT The exploratory objectives are: -to assess the effect of JCAR017 attributes on safety, pharmacokinetics (PK), and antitumor activity -to evaluate the immune responses directed against JCAR017 -to evaluate the role of tumor and the tumor microenvironment in mechanisms of response and resistance to JCAR017 -to evaluate the tumor and the tumor microenvironment in subjects treated according to SOC for correlates of efficacy within the SOC arm and for subjects who cross over to JCAR017 -to describe the effect of treatments directed at severe cytokine release syndrome (sCRS) and neurotoxicity and duration and severity of these events and whether these safety features are affected by initial SOC treatment for subjects that cross over to JCAR017 -to assess the safety and efficacy for subjects who crossed over to JCAR017

Treatments

Therapies

Medications

JCAR017 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Inclusion Criteria

> Between 18 years 75 years of age at the time of signing the informed consent form (ICF).

  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
  • 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.
  • Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
  • [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening. (Deauville score 4 or 5)
  • Adequate organ function
  • Participants must agree to use effective contraception

  • Exclusion Criteria

    > Participants not eligible for hematopoietic stem cell transplantation (HSCT).

  • Participants planned to undergo allogeneic stem cell transplantation.
  • Participants 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).
  • Participants with prior history of malignancies, other than aggressive R/R NHL, unless the participant has been free of the disease for ≥ 2 years with the exception of the following noninvasive malignancies: (a) Basal cell carcinoma of the skin (b) Squamous cell carcinoma of the skin (c) Carcinoma in situ of the cervix (d) Carcinoma in situ of the breast (e) Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative. (f) Other completely resected stage 1 solid tumor with low risk for recurrence
  • Treatment with any prior gene therapy product.
  • Participants who have received previous CD19-targeted therapy.
  • Participants with active hepatitis B, or active hepatitis C are excluded. Participants with negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are permitted. Participants 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. Participants with a history of or active human immunodeficiency virus (HIV) are excluded.
  • Participants with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
  • Active autoimmune disease requiring immunosuppressive therapy.
  • 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.
  • History or presence of clinically relevant central nervous system (CNS) pathology
  • Pregnant or nursing (lactating) women.

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