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A Study of Venetoclax in Combination With Obinutuzumab in Participants With Chronic Lymphocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01685892
First Posted: September 14, 2012
Last Update Posted: July 31, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
AbbVie (prior sponsor, Abbott)
Information provided by (Responsible Party):
Genentech, Inc.
September 12, 2012
September 14, 2012
July 31, 2017
November 29, 2012
April 2, 2019   (Final data collection date for primary outcome measure)
  • Percentage of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Schedule (Sch) A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days) ]
  • Maximum Tolerated Dose (MTD) of Venetoclax in Combination with Obinutuzumab [ Time Frame: Sch A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days) ]
  • Maximum tolerated dose [ Time Frame: Approximately 30 months ]
  • Safety: incidence of adverse events [ Time Frame: approximately 30 months ]
Complete list of historical versions of study NCT01685892 on ClinicalTrials.gov Archive Site
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Area Under the Concentration-Time Curve (AUC) of Venetoclax [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Maximal Plasma Concentration (Cmax) of Venetoclax [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Minimum Plasma Concentration (Cmin) of Venetoclax [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Cmax of Obinutuzumab [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Cmin of Obinutuzumab [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Percentage of Participants with Confirmed Complete Response (CR) as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Percentage of Participants with Objective Response (Partial Response [PR] or CR [Including Cytopenic CR] as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Duration of Objective Response as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Overall Survival [ Time Frame: Baseline up to death or end of study (up to approximately 6 years 4 months) ]
  • Progression-Free Survival as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Number of B-Cells [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Number of T-Cells [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Number of Natural Killer (NK) Cells [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Serum Immunoglobulin Level [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
Pharmacokinetics: Area under the concentration time curve [ Time Frame: Approximately 30 months ]
Not Provided
Not Provided
 
A Study of Venetoclax in Combination With Obinutuzumab in Participants With Chronic Lymphocytic Leukemia
A Phase Ib Multicenter Dose-Finding and Safety Study of Venetoclax and Obinutuzumab in Patients With Relapsed or Refractory or Previously Untreated Chronic Lymphocytic Leukemia
This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics of venetoclax (GDC-0199; ABT-199) administered in combination with obinutuzumab to participants with relapsed/refractory or previously untreated chronic lymphocytic leukemia (CLL). The study is comprised of two stages for each participant population: a dose-finding stage and a safety-expansion stage. The dose-finding stage will explore multiple doses of venetoclax to be used in combination with a fixed dose of obinutuzumab. The dose-finding stage will also explore two schedules for drug administration, Schedule A (venetoclax introduced before obinutuzumab) and Schedule B (venetoclax introduced after obinutuzumab).
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lymphocytic Leukemia, Chronic
  • Drug: Obinutuzumab
    Participants will receive IV infusion of obinutuzumab (100 milligrams [mg]) on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, and 1000 mg on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.
    Other Name: GA101; RO5072759
  • Drug: Venetoclax
    Participants will receive multiple doses of venetoclax orally once daily.
    Other Name: ABT-199, GDC-0199
  • Experimental: Dose-Finding: Schedule A: Relapsed/Refractory CLL
    All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • Experimental: Dose-Finding: Schedule B: Relapsed/Refractory CLL
    In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • Experimental: Dose-Finding: Schedule A: Previously Untreated CLL
    All 4 cohorts will begin venetoclax administration after the ramp-up period of 5 weeks. In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A, venetoclax will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • Experimental: Dose-Finding: Schedule B: Previously Untreated CLL
    In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B, venetoclax will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • Experimental: Safety Expansion: Relapsed/Refractory CLL
    In participants with relapsed/refractory CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax
  • Experimental: Safety Expansion: Previously Untreated CLL
    In participants with previously untreated CLL a recommended dose of venetoclax will be administered in combination with obinutuzumab in the safety expansion stage. Schedule A or B will be used for the expansion cohort after a review of available safety data from the dose finding stage.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
82
April 2, 2019
April 2, 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of relapsing/refractory or previously untreated chronic lymphocytic leukemia
  • Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (</=) 1
  • Adequate bone marrow function
  • Adequate coagulation, renal and hepatic function
  • For all participants, agreement to remain abstinent or use contraceptive methods that result in a failure rate of less than (<) 1% per year during the treatment period and for at least 90 days (30 days for women) after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer

Exclusion Criteria:

  • Participants who have undergone allogenic stem cell transplant are ineligible unless they meet the following criteria, a) participants who are off all immunosuppressive therapy, b) participants who have no signs and/or symptoms of acute or chronic graft versus host disease, or c) participants must have appropriate hematology counts
  • Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Investigational or anti-cancer therapy within 5 half-lives prior to the first dose of study drug
  • History of significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom,   United States
 
 
NCT01685892
GP28331
2012-002038-34 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Genentech, Inc.
Genentech, Inc.
AbbVie (prior sponsor, Abbott)
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP
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