An Open-label Phase I Drug-drug Interaction Study of Ofatumumab With Bendamustine for the Treatment of Subjects With Indolent B-cell Non-Hodgkin's Lymphoma
An Open-label Phase I Drug-drug Interaction Study of Ofatumumab With Bendamustine for the Treatment of Subjects With Indolent B-cell Non-Hodgkin's Lymphoma
The purpose of this study is to evaluate the potential drug-drug interactions between ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent B-cell non-Hodgkin's lymphoma (NHL).
The purpose of this study is to evaluate the potential drug-drug interactions between ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent B-cell non-Hodgkin's lymphoma (NHL). Ofatumumab and bendamustine will be administered alone and in combination in a two-arm, open-label study to evaluate the pharmacokinetic profile, safety, tolerability, and efficacy of ofatumumab and bendamustine.
The primary objective of the study is to evaluate pharmacokinetic parameters of ofatumumab and bendamustine alone and in combination. Secondary objectives are to evaluate safety, tolerability, and efficacy.
Inclusion Criteria:
Exclusion Criteria:
Subjects who failed to achieve a complete remission (CR) or partial remission (PR) or progressed within 6 months of last rituximab-containing therapy
Previous treatment with ofatumumab.
Prior bendamustine treatment not resulting in a complete remission and partial remission for at least 6 months.
Previous allogeneic stem cell transplant.
Previous autologous stem cell transplant.
High dose steroids greater than or equal to 100 mg prednisone/day (or equivalent) for greater than or equal to 7 consecutive days, given as concomitant medication, within 3 months prior to randomization. No more than 20 mg prednisone or equivalent daily at the time of randomization.
Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma as verified by biopsy confirmation.
Known central nervous system involvement by NHL.
Other past or current malignancy. Subjects who have been free of malignancy for at least 2 years, or have a 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 such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active Hepatitis B or C. Prophylactic antibiotics to prevent recurrent of a prior infection (such as shingles, sinusitis or upper respiratory infection) is allowed.
Clinically significant cardiac disease as judged by the investigator, including unstable angina, acute myocardial infarction within 6 months of randomization, and uncontrolled congestive heart failure (CHF) or arrhythmia. Patients with a history of CHF or arrhythmia are eligible if their cardiac disease is well controlled on a stable medical regimen.
History of significant cerebrovascular disease or event with significant symptoms or sequelae (as judged by the investigator).
Significant concurrent, uncontrolled medical condition that in the opinion of the investigator contraindicates participation this study.
Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg but Hepatitis B core antibody (HBcAb) positive (regardless of Hepatitis B surface antibody [HBsAb] status), a HB DNA test will be performed and if positive the subject will be excluded. If HBV DNA is negative, the subject may be included but must undergo Hepatitis B virus (HBV) DNA monitoring (see Section 7.7.5). Prophylactic antiviral therapy may be initiated at the discretion of the investigator.
Current active liver or biliary disease (subjects with Gilbert's syndrome or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable chronic liver disease per investigator assessment, are eligible).
Known human immunodeficiency virus (HIV) positive.
Screening laboratory values:
Known or suspected hypersensitivity to ofatumumab, bendamustine, or mannitol.
Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to Visit 1, whichever is longer or currently participating in any other interventional clinical study
Lactating women, women with a positive pregnancy test at Visit 1, or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception until 12 months after the last dose of study drug. Adequate contraception is defined in Section 8.1.