A Phase 1 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
Johns Hopkins Kimmel Cancer Center in Baltimore
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 40 subjects with relapsed or refractory non-Hodgkin's lymphoma. This study will consist of 2 distinct portions. The first portion of the study will evaluate the safety and pharmacokinetic profile of ABT-199 in approximately 18 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. The second portion of the study is an expanded safety cohort that will evaluate ABT-199 at the recommended Phase 2 dose defined in the first portion of the study, in combination with Bendamustine/Rituximab in approximately 20 Diffuse Large B-cell Lymphoma subjects.
Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Accepts Healthy Volunteers: No Criteria Inclusion Criteria Subject must be greater than or equal to 18 years of age. 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, received no more than 5 prior myelosuppressive/chemotherapy regimens, and require treatment in the opinion of the investigator. Subject must have relapsed following or be refractory to standard treatments such as Rituximab-Cyclophosphamide, Hydroxydaunomycin, Vincristine (Oncovin), Prednisone (R-CHOP); Rituximab-Cyclophosphamide, Vincristine (Oncovin), and Prednisone (R-CVP); or fludarabine-based regimens. 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 or small lymphocytic lymphoma. 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.
Experimental: Arm 1 Non-Hodgkin's Lymphoma (NHL) Drug: ABT-199 ABT-199 is taken orally once daily for 3 days out of each 28 day cycle. This is a dose escalation study, therefore the dose of ABT-199 will change throughout the study. Other Name: ABT-199 Drug: Bendamustine Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle. Other Name: Bendamustine Drug: Rituximab Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle. Other Name: Rituximab
09/26/2016 05:03 AM