A Study of Obinutuzumab (RO5072759) Plus Chemotherapy in Comparison With Rituximab Plus Chemotherapy Followed by Obinutuzumab or Rituximab Maintenance in Patients With Untreated Advanced Indolent Non-Hodgkin's Lymphoma (GALLIUM)

Roche

Status and phase: Completed; Phase 3

Conditions: Non-Hodgkin's Lymphoma

Treatments: Drug: Rituximab; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine; Drug: Bendamustine; Drug: Cyclophosphamide; Drug: Obinutuzumab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01332968

BO21223

2010-024132-41 (EudraCT Number)

Details and patient eligibility

About

This open-label, randomized study will assess the efficacy and safety of obinutuzumab (RO5072759) in combination with chemotherapy compared to rituximab (MabThera/Rituxan) with chemotherapy followed by obinutuzumab or rituximab maintenance in participants with untreated advanced indolent non-Hodgkin's lymphoma. After the end of the induction period, participants achieving response (Complete response [CR] or partial response [PR]) will undergo a maintenance period continuing on the randomized antibody treatment alone every 2 months until disease progression for a total of 2 years. Anticipated time on study treatment is up to approximately 2.5 years. After maintenance or observation, participants will be followed for 5 years until progression. After progression, participants will be followed for new anti-lymphoma therapy and overall survival until the end of the study.

Enrollment: 1,401 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Cluster of differentiation 20 (CD20)-positive indolent B-cell non-Hodgkin's lymphoma (follicular lymphoma or splenic, nodal or extranodal marginal zone lymphoma)
• Stage III or IV disease, or Stage II bulky disease (defined as tumor diameter greater than or equal to [>/=] 7 centimeters [cm])
• For participants with follicular lymphoma: requirement for treatment according to Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
• For participants with symptomatic splenic, nodal, or non-gastric extranodal marginal zone lymphoma: disease that is de novo or has relapsed following local therapy (i.e. surgery or radiotherapy) and requires therapy as assessed by the investigator
• At least one bi-dimensionally measurable lesion (greater than [>] 2 cm in its largest dimension by computed tomography [CT] scan or magnetic resonance imaging [MRI])
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Adequate hematologic function

Exclusion criteria

• Central nervous system lymphoma, leptomeningeal lymphoma, or histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
• Grade 3b follicular lymphoma, small lymphocytic lymphoma or Waldenström's macroglobulinaemia
• Ann Arbor Stage I disease
• History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
• Known hypersensitivity to any of the study drugs or sensitivity to murine products, or history of sensitivity to mannitol
• For participants with follicular lymphoma: prior treatment for non-Hodgkin's lymphoma with chemotherapy, immunotherapy, or radiotherapy
• For participants with non-follicular lymphoma: prior treatment with chemotherapy or immunotherapy
• Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle 1
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
• For participants who will be receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP): left ventricular ejection fraction (LVEF) less than (<) 50% by multiple-gated acquisition (MUGA) scan or echocardiogram
• History of prior other malignancy with the exception of curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study
• Known active infection, or major episode of infection within 4 week prior to the start of Cycle 1
• Vaccination with a live vaccine within 28 days prior to randomization
• Recent major surgery (within 4 weeks prior to start of Cycle 1), other than for diagnosis
• Abnormal laboratory values as defined by protocol for creatinine, creatinine clearance, aspartate transaminase (AST) or alanine transaminase (ALT), total bilirubin, international normalized ration (INR), partial thromboplastin time (PTT) or activated partial thromboplastin time (aPPT), unless these abnormalities are due to underlying lymphoma
• Positive test results for human immunodeficiency virus (HIV), human T-lymphotropic virus 1 (HTLV1), hepatitis C or chronic hepatitis B
• Pregnant or lactating women
• Life expectancy <12 months
• Participation in another clinical trial with drug intervention within 28 days prior to start of Cycle 1 and during study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,401 participants in 2 patient groups

Rituximab+Chemotherapy

Active Comparator group

Description:

Participants will receive either 8 cycles of rituximab along with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (21-day cycle) or 8 cycles of rituximab along with 8 cycles of cyclophosphamide, vincristine, and prednisone (CVP) (21-day cycles) or 6 cycles of rituximab along with 6 cycles of bendamustine (28-day cycle) during the induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive rituximab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.

Treatment:

Drug: Rituximab

Drug: Prednisone

Drug: Doxorubicin

Drug: Vincristine

Drug: Bendamustine

Drug: Cyclophosphamide

Obinutuzumab+Chemotherapy

Experimental group

Description:

Participants will receive either 8 cycles of obinutuzumab along with 6 cycles of CHOP (21-day cycle) or 8 cycles of obinutuzumab along with 8 cycles of CVP (21-day cycles) or 6 cycles of obinutuzumab along with 6 cycles of bendamustine (28-day cycle) during induction period. The induction period will be followed by either a maintenance or observation period for responders or non-responders, respectively. Responders will receive obinutuzumab monotherapy every 2 months for 2 years during the maintenance period. Non-responders will receive no protocol specified treatment during the 2-year observation period. Finally, participants will be followed during a 5-year follow-up period. The chemotherapy regimen (CHOP or CVP or bendamustine) for individual participant will be chosen by the site prior to initiation of the study.

Treatment:

Drug: Obinutuzumab

Drug: Prednisone

Drug: Doxorubicin

Drug: Vincristine

Drug: Bendamustine

Drug: Cyclophosphamide