A Study of Venetoclax (GDC-0199, ABT-199) in Combination With Bendamustine And MabThera/Rituxan in Participants With Chronic Lymphocytic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Genentech, Inc.
Sponsor:
Collaborator:
AbbVie (prior sponsor, Abbott)
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01671904
First received: August 10, 2012
Last updated: February 1, 2016
Last verified: February 2016
  Purpose
This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics of Venetoclax (GDC-0199, ABT-199) administered in combination with bendamustine and MabThera/Rituxan (rituximab) or bendamustine and obinutuzumab to participants with relapsed/refractory or previously untreated chronic lymphocytic leukemia.

Condition Intervention Phase
Lymphocytic Leukemia, Chronic
Drug: Bendamustine
Drug: Obinutuzumab
Drug: Rituximab
Drug: Venetoclax (ABT-199; GDC-0199)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IB, Open-Label Study Evaluating the Safety and Pharmacokinetics of Venetoclax (GDC-0199, ABT-199) in Combination With Bendamustine+Rituximab (BR) or Bendamustine+Obinutuzumab (BG) in Patients With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Overall Response Rate [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Duration of Response [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Percentage of Participants with Complete Response [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Changes in B-cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Changes in T-cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Changes in Natural Killer (NK) Cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Changes in Serum Immunoglobulin [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximal Plasma Concentration (Cmax) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Minimum Plasma Concentration (Cmin) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area Under the Concentration Time Curve [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: January 2014
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Label: 1 Dose-Finding: Schedule A: Relapsed/Refractory CLL
In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before bendamustine and rituximab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
90 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Bendamustine
70 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
375 mg/m^2 of rituximab administered by intravenous infusion on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Label: 2 Dose-Finding: Schedule B: Relapsed/Refractory CLL
In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after bendamustine and rituximab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
70 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
375 mg/m^2 of rituximab administered by intravenous infusion on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Label: 3 Dose-Finding: Schedule A: Previously Untreated CLL
In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before bendamustine and rituximab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
90 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
375 mg/m^2 of rituximab administered by intravenous infusion on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Label: 4 Dose-Finding: Schedule B: Previously Untreated CLL
In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose bendamustine and rituximab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after bendamustine and rituximab . Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
90 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
375 mg/m^2 of rituximab administered by intravenous infusion on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Label: 5 Dose-Finding: Schedule A (Optional): CLL
Optional study arm: In 4 cohorts of participants with relapsed/refractory or previously untreated CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose bendamustine and obinutuzumab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before bendamustine and obinutuzumab. Schedule A will be explored prior to Schedule B.
Drug: Bendamustine
90 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Obinutuzumab
100 mg of obinutuzumab administered by intravenous infusion on Day 1 of Cycle 1; 900 mg administered on Day 2 of Cycle 1; and 1000 mg administered on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Label: 6 Safety Expansion: Relapsed/Refractory CLL
In participants with relapsed/refractory CLL a recommended dose of venetoclax (GDC-0199; ABT-199) will be administered in combination with bendamustine and rituximab in the safety expansion stage.In participants with relapsed/refractory CLL a recommended dose of venetoclax (GDC-0199; ABT-199) will be administered in combination with bendamustine and rituximab in the safety expansion stage.
Drug: Bendamustine
70 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
375 mg/m^2 of rituximab administered by intravenous infusion on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Label: 7 Safety Expansion: Previously Untreated CLL
In participants with previously untreated CLL a recommended dose of venetoclax (GDC-0199; ABT-199) will be administered in combination with bendamustine and rituximab in the safety expansion stage.
Drug: Bendamustine
90 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Rituximab
375 mg/m^2 of rituximab administered by intravenous infusion on Day 1 of Cycle 1 and 500 mg/m^2 administered on Day 1 of Cycles 2-6.
Other Name: MabThera; Rituxan
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: Label: 8 Safety Expansion (Optional): Previously Untreated CLL
In participants with previously untreated CLL a recommended dose of venetoclax (GDC-0199; ABT-199) will be administered in combination with bendamustine and obinutuzumab in the safety expansion stage.
Drug: Bendamustine
90 mg/m^2 of bendamustine administered by intravenous infusion on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.
Drug: Obinutuzumab
100 mg of obinutuzumab administered by intravenous infusion on Day 1 of Cycle 1; 900 mg administered on Day 2 of Cycle 1; and 1000 mg administered on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (ABT-199; GDC-0199)
Multiple doses of venetoclax administered orally once daily.
Other Name: ABT-199; GDC-0199

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of relapsing/refractory or previously untreated chronic lymphocytic leukemia
  • Eastern Cooperative Oncology Group (ECOG) performance score of </=1
  • Adequate bone marrow function
  • Adequate renal and hepatic function

Exclusion Criteria:

  • Participants received an allogeneic stem cell transplant
  • Infection with human immunodeficiency virus, hepatitis B (eligible only if polymerase chain reaction [PCR] is negative for hepatitis B), or hepatitis C (eligible only if PCR is negative for hepatitis C ribonucleic acid)
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Investigational or anti-cancer therapy within 14 days of study start (30 days for biologic agents for anti-neoplastic intent)
  • History of significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease
  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: NCT01671904

Contacts
Contact: Reference Study ID Number: GO28440 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, California
Recruiting
La Jolla, California, United States, 92093
United States, Illinois
Recruiting
Harvey, Illinois, United States, 60426
United States, Michigan
Recruiting
Detroit, Michigan, United States, 48201
United States, Washington
Terminated
Spokane, Washington, United States, 99218
Terminated
Yakima, Washington, United States, 98902
Recruiting
Yakima, Washington, United States, 98902
France
Recruiting
Lille, France, 59037
Recruiting
Montpellier, France, 34295
Recruiting
Pierre Benite, France, 69495
Recruiting
Rouen, France, 76038
Germany
Recruiting
Freiburg, Germany, 79106
Terminated
Kiel, Germany, 24105
Recruiting
Köln, Germany, 50924
Recruiting
München, Germany, 80804
Recruiting
Ulm, Germany, 89081
Sponsors and Collaborators
Genentech, Inc.
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01671904     History of Changes
Other Study ID Numbers: GO28440  2012-002351-42 
Study First Received: August 10, 2012
Last Updated: February 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bendamustine
Nitrogen Mustard Compounds
Obinutuzumab
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 February 11, 2016