Randomized Phase III Study Using a Pet-driven Strategy and Comparing GA101 OR Rituximab Associated to a Chemotherapy Delivered Every 14 Days (ACVBP or CHOP) in DLBCL CD20+ Lymphoma Untreated Patients From 18 to 60 Presenting With 1 or More Adverse Prognostic Factors of the Age-adjusted IPI
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Enrollment
- 671
- Locations
- 122
- Primary Endpoint
- 2-year Event Free Survival
Study Overview
Brief Summary
This study is designed to investigate:
- the interest of a new monoclonal antibody (GA101)versus rituximab
- the interest of PET to identify early responders
Patients will receive either rituximab (standard treatment), either GA101 (study treatment), according to the randomization arm.
The monoclonal antibody will be associated to a chemotherapy: CHOP or ACVBP according to site's choice.A PET scan will be done before inclusion, after 2 chemotherapy cycles, and after 4 chemotherapy cycles, to identify early patients responders, for who consolidation with ASCT is not required.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically proven CD20+ diffuse large B cell lymphoma (WHO Classification)
- •Baseline PET scan available with at least one hypermetabolic lesion
- •Aged ≥ 18 years and ≤ 60 years
- •Eligible for autologous stem cell transplant
- •Patient not previously treated
- •Age adjusted International Prognostic Index (aa-IPI) equal to 1, 2 or 3
- •Life expectancy ≥ 3 months
- •Negative HIV, HBV (anti-HBc negativity) and HCV serologies before inclusion
- •Having signed a written informed consent
- •Having ability and willingness to comply with study protocol procedures
- •Men must agree to use a barrier method of contraception during the treatment period and until 3 months after the last dose of GA101 or rituximab, or ACVBP14 or CHOP14 chemotherapy, whichever is longer
- •Women of childbearing potential must agree to use an adequate method of contraception, such as oral contraceptives, intrauterine device, or barrier method of contraception during the treatment period and until 12 months after the last dose of GA101, Rituximab, ACVBP14, or CHOP14 chemotherapy, whichever is longer
Exclusion Criteria
- •Any other histological type of lymphoma
- •Any history of treated or non-treated indolent lymphoma. However, patients not previously diagnosed and having a diffuse large B-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included
- •Central nervous system or meningeal involvement by lymphoma
- •Contra-indication to any drug contained in the chemotherapy regimens
- •Poor cardiac function (LVEF < 50%) on echocardiogram or MUGA scan
- •Poor renal function (creatinine level > 150*mol/l or clearance < 30ml/min), poor hepatic function (total bilirubin level > 30µmol/l, transaminases > 2.5 X maximum normal level) unless these abnormalities are related to the lymphoma
- •Poor bone marrow reserve as defined by neutrophils < 1.5 G/L or platelets < 100 G/L, unless related to bone marrow infiltration
- •Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
- •Any serious active disease (according to the investigator's decision)
- •Treatment with any investigational drug within 30 days before planned first cycle of chemotherapy
- •Pregnant or lactating women
- •Adult patient under tutelage
- •Prior history of Progressive Multifocal Leukoencephalopathy (PML)
Arms & Interventions
GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Intervention: GA101 (Drug)
GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Intervention: Doxorubicin (Drug)
GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Intervention: Cyclophosphamide (Drug)
GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Intervention: Prednisone (Drug)
GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Intervention: Bleomycin (Drug)
GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Intervention: Vindesin (Drug)
GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Intervention: Vincristine (Drug)
Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Intervention: Rituximab (Drug)
Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Intervention: Doxorubicin (Drug)
Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Intervention: Cyclophosphamide (Drug)
Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Intervention: Prednisone (Drug)
Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Intervention: Bleomycin (Drug)
Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Intervention: Vindesin (Drug)
Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Intervention: Vincristine (Drug)
Outcomes
Primary Outcomes
2-year Event Free Survival
Time Frame: Up to 2 years
EFS is defined as PET positivity according to ΔSUVmax criteria after 2 or 4 induction cycles as defined by RAC (based on central PET review), progression or relapse according to Cheson 2007, modification of planned treatment out of progression or death of any cause.
Secondary Outcomes
- • Progression-Free Survival (PFS)(Up to 6.5 years)
- • Overall survival (OS)(Up to 6.5 years)
- Number of stem cell collected after GA101 treatment(Up to 3.5 years)
- • Blood samples and on tumor tissue biopsy(Up to 6.5 years)
- • Overall Response Rate and Best overall response after 4 cycles and end of treatment according to Cheson 1999 criteria(Up to 3.5 years)
- • Duration of response (DoR)(Up to 6.5 years)
- • Early metabolic response according to PET after 2 and 4 cycles(Up to 3.5 years)
- • Focus on subpopulation(Up to 6.5 years)
- • Overall Response rate and Best overall response after 4 cycles and end of treatment according to Cheson 2007 criteria(Up to 3.5years)