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GA In NEwly Diagnosed Diffuse Large B Cell Lymphoma (GAINED)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01659099
First Posted: August 7, 2012
Last Update Posted: March 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
  Purpose

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.


Condition Intervention Phase
Diffuse Large B Cell Lymphoma CD20 Positive Drug: GA101 Drug: Rituximab Drug: Doxorubicin Drug: Cyclophosphamide Drug: Prednisone Drug: Bleomycin Drug: Vindesin Drug: Vincristine Phase 3

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

Resource links provided by NLM:


Further study details as provided by The Lymphoma Academic Research Organisation:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • • 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 ]
    Response will be assessed after 4 cycles and again at the end of treatment, based on RAC assessment for PET 4 and investigator assessment for EoT PET. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 2007). Overall (CR//PR) response rates and Best Response Rate will be presented. Patient without response assessment (due to whatever reason) will be considered as non-responder.

  • • 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 ]
    Response will be assessed after 4 cycles and at the end of treatment, based on investigator assessment. Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999). Overall (CR/CRu/PR) response rates and Best Overall Response Rate will be presented. Patient without response assessment (due to whatever reason) will be considered as non-responder.

  • • Duration of response (DoR) [ Time Frame: Up to 6.5 years ]
    Duration of response is defined as the period from the time of attainment a CR or PR to the date of progression, relapse or death from any cause. Duration or response would be assessed as survival in the whole population, in the two inductive arms (R-Chemo14 vs GA101-Chemo14) For patients achieving a response but who have not progressed or relapsed or died at the time of analysis, DOR will be censored on the date of last disease assessment

  • • Progression-Free Survival (PFS) [ Time Frame: Up to 6.5 years ]
    Progression-Free Survival is defined as the period from the date of randomization to the date of first documented disease progression, relapse, or death from any cause. For patients who have not progressed, relapsed, or died at the time of analysis, PFS will be censored on the date of last disease assessment. If no tumor assessments were performed after the baseline visit, PFS will be censored at the time of randomization

  • • Overall survival (OS) [ Time Frame: Up to 6.5 years ]
    Overall survival is defined as the period from the date of randomization to the date of death from any cause. Alive patients at the time of the analysis will be censored at their last contact date

  • • Blood samples and on tumor tissue biopsy [ Time Frame: Up to 6.5 years ]
    Analysis on blood samples and tumor tissue biopsy will be driven, in order to explore prognosis factors of the patients and their tumors that influence treatment response based on PET assessment and prognosis

  • • Focus on subpopulation [ Time Frame: Up to 6.5 years ]

    Duration of response, PFS and OS will be performed according to treatment arms (R-Chemo14 vs GA101-Chemo14) on different analysis populations. The subpopulations are based on the outcome during the induction phase and a statistical bias could be introduced as subpopulations have not been defined at baseline.

    • Population with a Δ SUVmaxPET0-2≤66% (slow and intermediate responders),
    • Population with a Δ SUVmaxPET0-2>66% (fast responders),
    • Patients submitted to autologous stem cell transplant (PFS and OS only)

  • Number of stem cell collected after GA101 treatment [ Time Frame: Up to 3.5 years ]
    Number of stem cell collected after GA101 administration Number of required collects to achieve 3Mcells/kg.

  • • Early metabolic response according to PET after 2 and 4 cycles [ Time Frame: Up to 3.5 years ]
    Based on results of central PET review


Estimated Enrollment: 670
Study Start Date: September 2012
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Drug: GA101
in GA-ACBVP or in GA-CHOP 1000 mg on D1 and D8 (D8 in cycle 1 and 2)
Other Names:
  • obinutuzumab
  • Gazivaro
Drug: Doxorubicin
in ACBVP : 75 mg/m² on D1 in CHOP : 50 mg/m² on D1
Drug: Cyclophosphamide
in ACBVP : 1200 mg/m² on D1 in CHOP : 750 mg/m² on D1
Drug: Prednisone
in ACBVP : 60 mg/m² from D1 to D5 in CHOP : 40 mg/m² from D1 to D5
Drug: Bleomycin
in ACBVP 10 mg from D1 to D5
Drug: Vindesin
in ACBVP 2 mg/m² from D1 to D5
Drug: Vincristine
in CHOP 1,4 mg/m² on D1
Active Comparator: Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Drug: Rituximab
in R-ACBVP or in R-CHOP 375 mg/m² on D1
Other Name: Mabthera
Drug: Doxorubicin
in ACBVP : 75 mg/m² on D1 in CHOP : 50 mg/m² on D1
Drug: Cyclophosphamide
in ACBVP : 1200 mg/m² on D1 in CHOP : 750 mg/m² on D1
Drug: Prednisone
in ACBVP : 60 mg/m² from D1 to D5 in CHOP : 40 mg/m² from D1 to D5
Drug: Bleomycin
in ACBVP 10 mg from D1 to D5
Drug: Vindesin
in ACBVP 2 mg/m² from D1 to D5
Drug: Vincristine
in CHOP 1,4 mg/m² on D1

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01659099


  Show 122 Study Locations
Sponsors and Collaborators
The Lymphoma Academic Research Organisation
Hoffmann-La Roche
Investigators
Study Chair: Olivier Casasnovas, MD Lymphoma Study Association
Study Chair: Steven Le Gouill, MD Lymphoma Study Association
  More Information

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT01659099     History of Changes
Other Study ID Numbers: GAINED
First Submitted: July 4, 2012
First Posted: August 7, 2012
Last Update Posted: March 13, 2017
Last Verified: March 2017

Keywords provided by The Lymphoma Academic Research Organisation:
DLBCL
aa-IPI > or equal to 1
Diagnosis
18 to 60 years
Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Obinutuzumab
Doxorubicin
Prednisone
Vincristine
Bleomycin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors