Ofatumumab Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell NHL Unresponsive to Rituxtherapy (A+B)

Novartis

Status and phase: Terminated; Phase 3

Conditions: Lymphoma, Follicular

Treatments: Drug: Bendamustine infusion; Drug: Ofatumumab; Drug: Ofatumumab and Bendamustine infusions (Arm A); Drug: Bendamustine infusion (Arm B)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01077518

2008-004177-17 (EudraCT Number)

COMB157E2301 (Other Identifier)

110918

Details and patient eligibility

About

The purpose of this study was to evaluate the safety and efficacy of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Full description

Ofatumumab is an anti-CD20 monoclonal antibody shown to have monotherapy activity in patients with follicular lymphoma that has relapsed following rituximab-containing therapy. Bendamustine was approved by FDA for the treatment of in patients with indolent B-cell Non-Hodgkin's Lymphoma (NHL) that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Biologics have demonstrated enhanced efficacy when added to chemotherapeutic combinations in the frontline treatment for indolent NHL. The combination of ofatumumab and bendamustine may provide additional clinical benefit and efficacy to those who no longer respond to rituximab or rituximab-containing regimens.

The objective of this study is to determine the effect of ofatumumab and bendamustine combination therapy in patients with indolent B-cell NHL that did not respond to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment.

Enrollment: 346 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Indolent lymphoma including Grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; Stages III-IV, or bulky disease, Stage II. Tumor verified CD20+ and CT imaging done at screening verifying disease
• Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of treatment with rituximab or a rituximab-containing regimen
• Indolent lymphoma including grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; stages III-IV, or bulky disease stage II (i.e. as any single mass > 5 cm in any direction)
• ECOG Performance Status of 0, 1, or 2
• Life expectancy of at least 6 months
• 18 years or older
• Signed, written informed consent

Exclusion criteria

• Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma
• Previous allogeneic stem cell transplant
• Previous autologous stem cell transplant, fludarabine therapy, or radioimmunotherapy in the past 12 months
• Previous external beam radiation therapy to the pelvis. Previous external beam radiation therapy for bony disease to the cranium, mediastinum, and axilla, or to two or to more than 3 vertebral bodies
• High dose steroids greater to or equal to 60 mg prednisone/day (or equivalent) within 3 months of randomization. No more than 10 mg prednisone (or equivalent) daily at the time of randomization
• Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months
• Treatment with anti-CD20 monoclonal antibody within 3 months of randomization
• Known CNS involvement of indolent lymphoma
• Other past or current malignancy. Subjects free of malignancy for at least 5 years or have history of definitively treated non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
• Clinically significant cardiac disease
• History of significant cerebrovascular disease or event with significant symptoms
• Positive serology for Hepatitis B
• Current active liver or biliary disease (except Gibber's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease)
• Known HIV positive
• Abnormal/inadequate blood values, liver and kidney function
• Current participation in other clinical study
• Inability to comply with the protocol activities
• Lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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346 participants in 2 patient groups

Ofatumumab and Bendamustine (Arm A)

Experimental group

Description:

Up to 8 cycles of bendamustine (90 mg/m2) on Days 1,2 every 21 days with12 doses of ofatumumab (1000 mg, Day 1 q21 days when with bendamustine and q28 days when given as monotherapy)

Treatment:

Drug: Ofatumumab

Drug: Ofatumumab and Bendamustine infusions (Arm A)

Bendamustine (Arm B)

Active Comparator group

Description:

Up to 8 cycles of bendamustine (120 mg/m2) on Days 1,2 every 21 days

Treatment:

Drug: Ofatumumab

Drug: Bendamustine infusion (Arm B)

Drug: Bendamustine infusion