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
- Interventions
- Registration Number
- NCT01594229
- Lead Sponsor
- AbbVie
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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.
-
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).
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 ABT-199 Non-Hodgkin's Lymphoma (NHL) Arm 1 Rituximab Non-Hodgkin's Lymphoma (NHL) Arm 1 Bendamustine Non-Hodgkin's Lymphoma (NHL)
- Primary Outcome Measures
Name Time Method Determination of peak concentration (Cmax), trough concentration (Ctrough) and/or area under the concentration versus time curve (AUC) of ABT-199, Bendamustine and Rituximab in the dose escalation cohort Up to Cycle 6 for ABT-199 and Bendamustine, Up to Cycle 11 for Rituximab Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, or concomitant medication, will be considered a dose limiting toxicity
Determination of the maximum tolerated dose of ABT-199 when administered with Bendamustine and Rituximab in subjects with relapsed or refractory non-Hodgkin's lymphoma 3 days of study drug administration within the 28-day cycle at the designated cohort dose Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, or concomitant medication, will be considered a dose limiting toxicity
Determination of the recommended Phase 2 dose of ABT-199 when administered with Bendamustine and Rituximab in subjects with relapsed or refractory non-Hodgkin's lymphoma 3 days of study drug administration within the 28-day cycle at the designated cohort dose Protocol-defined events, which can not be attributed by the investigator to a clearly identifiable cause such as tumor progression, concurrent illness, or concomitant medication, will be considered a dose limiting toxicity
Number of participants with adverse events as a measure of safety and tolerability First 5 days of study drug administration, weekly through Cycle 2 and then Day 1 of each Cycle for an anticipated maximum duration of 6 months Adverse event monitoring, vital signs, physical examination, lymphocyte enumeration, 12-lead ECG, 2D echocardiogram/multiple gated acquisition scan (MUGA), and laboratory assessments
- Secondary Outcome Measures
Name Time Method Evaluate preliminary data regarding progression-free survival when ABT-199 is administered in combination with Bendamustine and Rituximab Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter Tumor response or clinical disease progression
Evaluate preliminary data regarding time to tumor progression when ABT-199 is administered in combination with Bendamustine and Rituximab. Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter Tumor response or clinical disease progression
Evaluate preliminary data regarding overall survival and duration of overall response when ABT-199 is administered in combination with Bendamustine and Rituximab. Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter Tumor response or clinical disease progression
Evaluate preliminary data regarding objective response rate when ABT-199 is administered in combination with Bendamustine and Rituximab Tumor Assessments: Approximately every 2 cycles through Cycle 17 then every 6 cycles thereafter; Clinical Disease Assessment: Weekly through Cycle 2, then every cycle thereafter Tumor response or clinical disease progression
Trial Locations
- Locations (8)
Johns Hopkins University /ID# 67345
🇺🇸Baltimore, Maryland, United States
Emory University Hospital /ID# 67349
🇺🇸Atlanta, Georgia, United States
Georgia Regents University /ID# 67342
🇺🇸Augusta, Georgia, United States
Ucsd /Id# 67350
🇺🇸La Jolla, California, United States
University of California, Los Angeles /ID# 67343
🇺🇸Los Angeles, California, United States
Ingalls Memorial Hosp /ID# 67344
🇺🇸Harvey, Illinois, United States
Henry Ford Health System /ID# 67346
🇺🇸Detroit, Michigan, United States
University of Texas MD Anderson Cancer Center /ID# 69222
🇺🇸Houston, Texas, United States