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
Conditions: official terms
Lymphoma - Lymphoma, Non-Hodgkin
Conditions: Keywords
Safety, Maximum Tolerated Dose, ABT-199, Non-Hodgkin's Lymphoma, Cancer, Pharmacokinetics, Preliminary Efficacy, Bendamustine, Rituximab
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: ABT-199 Type: Drug
Name: Bendamustine Type: Drug
Name: Rituximab Type: Drug
Overall Status
Recruiting
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 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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.
Locations
Site Reference ID/Investigator# 67350
La Jolla, California, United States
Status: Recruiting
Site Reference ID/Investigator# 67343
Los Angeles, California, United States
Status: Recruiting
Site Reference ID/Investigator# 67349
Atlanta, Georgia, United States
Status: Recruiting
Site Reference ID/Investigator# 67342
Augusta, Georgia, United States
Status: Withdrawn
Site Reference ID/Investigator# 67344
Harvey, Illinois, United States
Status: Recruiting
Site Reference ID/Investigator# 67345
Baltimore, Maryland, United States
Status: Recruiting
Site Reference ID/Investigator# 67346
Detroit, Michigan, United States
Status: Recruiting
Site Reference ID/Investigator# 69222
Houston, Texas, United States
Status: Recruiting
Start Date
June 2012
Completion Date
January 2016
Sponsors
AbbVie (prior sponsor, Abbott)
Source
AbbVie
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page