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Completed

NCT Number: NCT01594229

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

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.

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Key information

Age range

18 year–99 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Ucsd /Id# 67350, La Jolla, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ABT-199

Drug

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.

Rituximab

Drug

Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle.

Bendamustine

Drug

Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle.

Primary outcomes

  1. 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

    Time frame: 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

  2. 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

    Time frame: 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

  3. Number of participants with adverse events as a measure of safety and tolerability

    Time frame: 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

  4. 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

    Time frame: 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

Secondary outcomes

  1. Evaluate preliminary data regarding progression-free survival when ABT-199 is administered in combination with Bendamustine and Rituximab

    Time frame: 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

  2. Evaluate preliminary data regarding overall survival and duration of overall response when ABT-199 is administered in combination with Bendamustine and Rituximab.

    Time frame: 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

  3. Evaluate preliminary data regarding objective response rate when ABT-199 is administered in combination with Bendamustine and Rituximab

    Time frame: 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

  4. Evaluate preliminary data regarding time to tumor progression when ABT-199 is administered in combination with Bendamustine and Rituximab.

    Time frame: 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

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Collaborators

  • Genentech, Inc.

Registry information

Official study title

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

Important dates

Study start
2012
Primary completion
2020
Study completion
2020
First posted
May 9, 2012
Registry last updated
Aug 2, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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