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

Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • Subject is ≥ 18 years and ≤ 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.
  • Adequate organ function
  • Participants must agree to use effective contraception

Exclusion Criteria

  • Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
  • Subjects planned to undergo allogeneic stem cell transplantation.
  • Subjects with, primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus) positive DLBCL of the elderly and Burkitt lymphoma.
  • 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
  • Treatment with any prior gene therapy product.
  • Subjects who have received previous CD19-targeted therapy.
  • History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
  • Subjects 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.

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Active
Name Not Available

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: UCSF Clinical Trials
Phone: 877-827-3222
Email: cancertrials@ucsf.edu

Florida

Jacksonville
Mayo Clinic in Florida
Status: Active
Name Not Available

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Approved
Name Not Available

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: Active
Name Not Available
Massachusetts General Hospital Cancer Center
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Minnesota

Minneapolis
University of Minnesota / Masonic Cancer Center
Status: Active
Name Not Available
Rochester
Mayo Clinic
Status: Active
Name Not Available

Nebraska

Omaha
University of Nebraska Medical Center
Status: Active
Contact: Matthew Alexander Lunning
Phone: 402-559-5166
Email: mlunning@unmc.edu

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Name Not Available

Oregon

Portland
OHSU Knight Cancer Institute
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Virginia

Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: Active
Contact: Kathryn Stauffer Candler
Phone: 804-828-4732
Email: kcandler@vcu.edu

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Celgene

Trial IDs

Primary ID JCAR017-BCM-003
Secondary IDs NCI-2018-02503, 2018-000929-32, U1111-1213-1944
Clinicaltrials.gov ID NCT03575351