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 currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by AbbVie
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: August 18, 2014
Last verified: August 2014
  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 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.


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 1b 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

  • Determination of peak concentration (Cmax) and/or trough concentration (Ctrough) of ABT-199, Bendamustine and Rituximab in the safety expansion cohort [ Time Frame: Up to Cycle 6 for ABT-199, Bendamustine and Rituximab ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of ABT-199, bendamustine and rituximab will be collected at designated time points

  • 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: January 2016
Estimated Primary Completion Date: January 2015 (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 and older
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

Contacts
Contact: Diane D'Amico, BS 847-937-5029 diane.damico@abbvie.com
Contact: Mike Dawson 847-938-9467 michael.dawson@abbvie.com

Locations
United States, California
Site Reference ID/Investigator# 67350 Recruiting
La Jolla, California, United States, 92093-0820
Principal Investigator: Site Reference ID/Investigator# 67350         
Site Reference ID/Investigator# 67343 Recruiting
Los Angeles, California, United States, 90095
Principal Investigator: Site Reference ID/Investigator# 67343         
United States, Georgia
Site Reference ID/Investigator# 67349 Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Site Reference ID/Investigator# 67349         
Site Reference ID/Investigator# 67342 Withdrawn
Augusta, Georgia, United States, 30912
United States, Illinois
Site Reference ID/Investigator# 67344 Recruiting
Harvey, Illinois, United States, 60426
Principal Investigator: Site Reference ID/Investigator# 67344         
United States, Maryland
Site Reference ID/Investigator# 67345 Recruiting
Baltimore, Maryland, United States, 21231
Principal Investigator: Site Reference ID/Investigator# 67345         
United States, Michigan
Site Reference ID/Investigator# 67346 Recruiting
Detroit, Michigan, United States, 48202
Principal Investigator: Site Reference ID/Investigator# 67346         
United States, Texas
Site Reference ID/Investigator# 69222 Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Site Reference ID/Investigator# 69222         
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Genentech, Inc.
Investigators
Study Director: David Chien, MD AbbVie
  More Information

No publications provided

Responsible Party: AbbVie ( 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: August 18, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 23, 2014