Overview

This trial is active, not recruiting.

Condition diffuse large b cell lymphoma cd20+
Treatment pet driven strategy for consolidation phase treatment
Phase phase 3
Sponsor The Lymphoma Academic Research Organisation
Collaborator Hoffmann-La Roche
Start date September 2012
End date February 2019
Trial size 670 participants
Trial identifier NCT01659099, GAINED

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
GA101 - Chemotherapy (ACVBP or CHOP)
pet driven strategy for consolidation phase treatment Consolidation treatment based on PET central review
PET scan evaluation is done after 2 and 4 cycles during the induction phase. According to a based on ΔSUVmaxPET0-2 and ΔSUVmaxPET0-4 judgment, consolidation treatment will be adaptated: If ΔSUVmaxPET0-2≤66%, PET 2 is positive; if ΔSUVmaxPET0-2>66%, PET 2 is negative If ΔSUVmaxPET0-4≤70%, PET 4 is positive; if ΔSUVmaxPET0-4>70%, PET 4 is negative According to the PET2/4 result, treatment during the consolidation phase will be adaptated as following: PET2-/PET4-: fast responders: patient will received consolidation treatment GA101-(CHOP or ACVBP)or rituximab -(CHOP or ACVBP) PET2+/PET 4-: slow responders: patient will received autologous stem cell transplant PET2- or PET2+/PET4+: patient will withdraw the study and treated according to local practice.
(Active Comparator)
Rituximab - Chemotherapy (ACVBP or CHOP)
pet driven strategy for consolidation phase treatment Consolidation treatment based on PET central review
PET scan evaluation is done after 2 and 4 cycles during the induction phase. According to a based on ΔSUVmaxPET0-2 and ΔSUVmaxPET0-4 judgment, consolidation treatment will be adaptated: If ΔSUVmaxPET0-2≤66%, PET 2 is positive; if ΔSUVmaxPET0-2>66%, PET 2 is negative If ΔSUVmaxPET0-4≤70%, PET 4 is positive; if ΔSUVmaxPET0-4>70%, PET 4 is negative According to the PET2/4 result, treatment during the consolidation phase will be adaptated as following: PET2-/PET4-: fast responders: patient will received consolidation treatment GA101-(CHOP or ACVBP)or rituximab -(CHOP or ACVBP) PET2+/PET 4-: slow responders: patient will received autologous stem cell transplant PET2- or PET2+/PET4+: patient will withdraw the study and treated according to local practice.

Primary Outcomes

Measure
2-year Event Free Survival
time frame: Up to 2 years

Secondary Outcomes

Measure
• Overall Response rate and Best overall response after 4 cycles and end of treatment according to Cheson 2007 criteria
time frame: Up to 3.5years
• Overall Response Rate and Best overall response after 4 cycles and end of treatment according to Cheson 1999 criteria
time frame: Up to 3.5 years
• Duration of response (DoR)
time frame: Up to 6.5 years
• Progression-Free Survival (PFS)
time frame: Up to 6.5 years
• Overall survival (OS)
time frame: Up to 6.5 years
• Blood samples and on tumor tissue biopsy
time frame: Up to 6.5 years
• Focus on subpopulation
time frame: Up to 6.5 years
Number of stem cell collected after GA101 treatment
time frame: Up to 3.5 years
• Early metabolic response according to PET after 2 and 4 cycles
time frame: Up to 3.5 years

Eligibility Criteria

Male or female participants from 18 years up to 60 years old.

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)

Additional Information

Official title 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 information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by The Lymphoma Academic Research Organisation.