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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 study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01594229
First received: April 20, 2012
Last updated: April 20, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: ABT-199
Drug: Bendamustine
Drug: Rituximab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 3 days of study drug administration within the 28-day cycle at the designated cohort dose ] [ Designated as safety issue: Yes ]
    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 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 ] [ Designated as safety issue: No ]
    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 [ 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 ] [ Designated as safety issue: Yes ]
    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:
  • 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 ] [ Designated as safety issue: No ]
    Tumor response or clinical disease progression

  • 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 ] [ Designated as safety issue: No ]
    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. [ 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 ] [ Designated as safety issue: No ]
    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. [ 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 ] [ Designated as safety issue: No ]
    Tumor response or clinical disease progression


Estimated Enrollment: 60
Study Start Date: June 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Bendamustine
Bendamustine will be given by intravenous infusion for 2 days out of each 28 day cycle.
Drug: Rituximab
Rituximab will be given by intravenous infusion for 1 day out of each 28 day cycle.

  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594229

Locations
United States, California
Site Reference ID/Investigator# 67350
La Jolla, California, United States, 92093-0820
Site Reference ID/Investigator# 67343
Los Angeles, California, United States, 90095
United States, Georgia
Site Reference ID/Investigator# 67349
Atlanta, Georgia, United States, 30322
United States, Illinois
Site Reference ID/Investigator# 67344
Harvey, Illinois, United States, 60426
United States, Maryland
Site Reference ID/Investigator# 67345
Baltimore, Maryland, United States, 21231
United States, Michigan
Site Reference ID/Investigator# 67346
Detroit, Michigan, United States, 48202
United States, Texas
Site Reference ID/Investigator# 69222
Houston, Texas, United States, 77030
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Genentech, Inc.
Investigators
Study Director: Adam Petrich, MD AbbVie
  More Information

Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT01594229     History of Changes
Other Study ID Numbers: M12-630 
Study First Received: April 20, 2012
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by AbbVie:
ABT-199
Cancer
Preliminary Efficacy
Non-Hodgkin's Lymphoma
Rituximab
Bendamustine
Pharmacokinetics
Maximum Tolerated Dose
Safety

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bendamustine Hydrochloride
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2016