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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by The Lymphoma Academic Research Organisation
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier:
NCT01659099
First received: July 4, 2012
Last updated: June 10, 2014
Last verified: June 2014
  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+
Other: PET driven strategy for consolidation phase treatment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GA101
GA101 - Chemotherapy (ACVBP or CHOP)
Other: PET driven strategy for consolidation phase treatment

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.
Other Name: Consolidation treatment based on PET central review
Active Comparator: Rituximab
Rituximab - Chemotherapy (ACVBP or CHOP)
Other: PET driven strategy for consolidation phase treatment

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.
Other Name: Consolidation treatment based on PET central review

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01659099

Contacts
Contact: Alexia Schwartzmann +33 4 72 66 93 33 alexia.schwartzmann@lysarc.org

  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

No publications provided

Responsible Party: The Lymphoma Academic Research Organisation
ClinicalTrials.gov Identifier: NCT01659099     History of Changes
Other Study ID Numbers: GAINED
Study First Received: July 4, 2012
Last Updated: June 10, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
Belgium: Ethics Committee
Belgium: Federal Agency for Medicinal Products and Health Products
Portugal: Ethics Committee for Clinical Research
Portugal: National Pharmacy and Medicines Institute

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
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014