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A Global Randomized Multicenter Phase 3 Trial of JCAR017 Compared to Standard of Care in Adult Subjects With High-risk, Second-line, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas (TRANSFORM)

Trial of JCAR017 Compared to Standard of Care in Adult Subjects With High-risk, Second-line, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas (JCAR017-BCM-003)

Nishio Mitsufumi

Bristol-Myers Squibb

1-2-1 Otemachi, Chiyoda-ku, Tokyo

mg-jp-clinical_trial@bms.com

Nishio Mitsufumi

Bristol-Myers Squibb

1-2-1 Otemachi, Chiyoda-ku, Tokyo

+81-120-093-507

MG-JP-RCO-JRCT@bms.com

completed

Aug. 30, 2019

Interventional

Phase 3, Randomized, Open-label, Parallel-group, Multi-center trial

treatment purpose

2

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

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.

Both

Relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphomas

Investigational material(s)
Generic name etc: JCAR017
INN of investigational material: lisocabtagene maraleucel
Therapeutic category code: 429 Other antitumor agents
Dosage and Administration for Investigational material: Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) concurrently followed by JCAR017 infusion at a dose of 1x10^8 CAR+ T cells.

Control material(s)
Generic name etc: Standard of care (SOC)
INN of investigational material: -
Therapeutic category code: 429 Other antitumor agents
Dosage and Administration for Investigational material: Standard of care (SOC) salvage therapy (R-DHAP, R-ICE or R-GDP) followed by High-dose chemotherapy (HDCT) and Hematopoietic stem cell transplant (HSCT)

Efficacy
- Event-free survival (EFS)

Safety
Efficaty
- Complete response rate (CRR)
- Progression-free survival (PFS)
- Overall survival (OS)
- Overall response rate (ORR)
- Duration of response (DOR)
etc.

+81-3-3588-1111

July. 02, 2019