Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.
  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 of the elderly and Burkitt lymphoma.
  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:
  5. Basal cell carcinoma of the skin
  6. Squamous cell carcinoma of the skin
  7. Carcinoma in situ of the cervix
  8. Carcinoma in situ of the breast
  9. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
  10. Other completely resected stage 1 solid tumor with low risk for recurrence
  11. Treatment with any prior gene therapy product.
  12. Subjects who have received previous CD19-targeted therapy.
  13. History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
  14. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
  15. Active autoimmune disease requiring immunosuppressive therapy.
  16. 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.
  17. History or presence of clinically relevant central nervous system (CNS) pathology
  18. Pregnant or nursing (lactating) women.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Arm A - Standard of Care (SOC)
Subjects should receive SOC (R-DHAP, R-ICE or R-GDP) followed by HDCT (BEAM) and HSCT. Standard of care regimen will be administered as per investigator decision.
  • Drug: Standard of Care
    Standard of Care
Experimental
Arm B - JCAR017
Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently followed by JCAR017 infusion.
  • Genetic: JCAR017
    JCAR017
    Other names:
    • lisocabtagene maraleucel or liso-cel

Recruiting Locations

Massachusetts General Hospital / Dana-Farber Cancer Institute
Boston, Massachusetts 02114

More Details

NCT ID
NCT03575351
Status
Recruiting
Sponsor
Celgene

Study Contact

Associate Director Clinical Trial Disclosure
1-888-260-1599
clinicaltrialdisclosure@celgene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.