Resumen

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.

Descripción detallada

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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
years or older
Signed, written informed consent

Criterios de exclusión

Previous allogeneic stem cell transplant
Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma
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

Intervenciones

drug

Ofatumumab

Ofatumumab was a liquid concentrate solution for infusion presented in glass vials containing 50 mL of solution at a concentration of 20 mg/mL to provide 1000 mg per vial. The ofatumumab infusions were prepared in 1000 mL sterile, pyrogen-free 0.9% NaCl to yield a 1 mg/mL ofatumumab concentration infusion.

drug

Bendamustine infusion

Bendamustine 100 mg/vial, injection

drug

Ofatumumab and Bendamustine infusions (Arm A)

Up to 8 cycles of Bendamustine (90 mg/m2 Days 1 and 2, every 21 days) given in combination with 12 doses of ofatumumab (1000 mg). Ofatumumab will be given on day 1 of each cycle of bendamustine as long as patients in Arm A receive bendamustine. Once patients in Arm A complete bendamustine therapy, the remaining doses of ofatumumab will be given monthly until all 12 doses are completed.

drug

Bendamustine infusion (Arm B)

Bendamustine (120 mg/m2 Days 1 and 2, every 21 days, up to 8 cycles).

Ubicaciones

Novartis Investigative Site

Capital Federal, Buenos Aires, Argentina

Novartis Investigative Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Novartis Investigative Site

Derqui, Pilar, Buenos Aires, Argentina

Novartis Investigative Site

La Plata, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, Argentina

Randomized Open Label of Ofatumumab and Bendamustine Combination Compared With Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin's Lymphoma Unresponsive to Rituximab or a Rituximab-Containing Regimen During or Within Six Months of Treatment

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Ofatumumab

Bendamustine infusion

Ofatumumab and Bendamustine infusions (Arm A)

Bendamustine infusion (Arm B)

Ubicaciones

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Novartis Investigative Site

Patrocinadores