a study evaluating the safety and pharmacokinetics of abt-199 in combination with bendamustine/rituximab (br) in subjects with relapsed or refractory non-hodgkin's lymphoma

Conditions: Non-Hodgkin's Lymphoma

Summary: this is a phase 1, open-label, multicenter study evaluating the safety, pharmacokinetic profile, and preliminary efficacy of abt-199 in combination with bendamustine/rituximab in approximately 60 subjects with relapsed or refractory non-hodgkin's lymphoma. this study will evaluate the safety and pharmacokinetic profile of abt-199 in approximately 60 subjects when administered in combination with bendamustine/rituximab following a dose escalation scheme, with the objective of defining the dose limiting toxicity and the maximum tolerated dose.


Eligibility criteria:
inclusion criteria: * subject must have histologically documented diagnosis of non-hodgkin's lymphoma as defined by a b-cell neoplasm in the world health organization classification scheme except as noted in exclusion criteria. * subject (non-diffuse large b-cell lymphoma) must have relapsed or refractory non-hodgkin's lymphoma, and require treatment in the opinion of the investigator. * subject with diffuse large b-cell lymphoma must have relapsed diffuse large b-cell lymphoma or must have progressed after salvage therapy (with or without standard chemotherapy) for diffuse large b-cell lymphoma. the subject must have received first line therapy with rituximab-cyclophosphamide, hydroxydaunomycin, vincristine (oncovin), prednisone (r-chop) \[or a similar standard rituximab-containing front-line chemoimmunotherapy regimen including, but not limited to etoposide, prednisone, vincristine (oncovin), cyclophosphamide, doxorubicin (hydrochloride) + rituximab (epoch + r); rituximab, cyclophosphamide, etoposide, procarbazine, prednisone (rcepp); rituximab, cyclophosphamide, mitoxantrone (novantrone), vincristine (oncovin), prednisone (rcnop); dose-adjusted-etoposide, prednisone, vincristine(oncovin), cyclophosphamide, doxorubicin (hydrocloride) (da-epoch); and rituximab, cyclophosphamide, etoposide, vincristine (oncovin), prednisone (rceop)\]. * subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at screening. exclusion criteria: * subject has been diagnosed with post-transplant lymphoproliferative disease, burkitt's lymphoma, burkitt-like lymphoma, lymphoblastic lymphoma/leukemia, chronic lymphocytic leukemia, small lymphocytic lymphoma or mantle cell lymphoma (mcl). * subject has refractory diffuse large b-cell lymphoma, defined as meeting any of the following criteria: * subject progressed during or within 3 months of completion of a planned course of first-line therapy with rituximab-cyclophosphamide, hydroxydaunomycin, vincristine (oncovin), prednisone (r-chop) or an equivalent regimen; * subject had no response (i.e., stable disease only) to first-line therapy with r-cyclophosphamide, hydroxydaunomycin, vincristine (oncovin), prednisone (r-chop) or an equivalent regimen; * subject progressed during or within 2 months of completion of their last planned course of salvage therapy with chemotherapy (with or without rituximab, may include autologous stem cell transplant). * subject has tested positive for human immunodeficiency virus (hiv). * subject has a cardiovascular disability status of new york heart association class greater or equal to 2. class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity, results in fatigue, palpitations, dyspnea or anginal pain. * subject has a significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, or hepatic disease that in the opinion of the investigator would adversely affect his/her participating in this study.

Keywords: pharmacokinetics maximum tolerated dose safety bendamustine non-hodgkin's lymphoma rituximab abt-199 cancer preliminary efficacy