A Study of Venetoclax (GDC-0199; ABT-199) in Combination With Obinutuzumab in Participants With Chronic Lymphocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AbbVie (prior sponsor, Abbott)
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01685892
First received: September 12, 2012
Last updated: August 1, 2016
Last verified: August 2016

September 12, 2012
August 1, 2016
November 2012
May 2019   (final data collection date for primary outcome measure)
Maximum Tolerated Dose (MTD) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Maximum tolerated dose [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Safety: incidence of adverse events [ Time Frame: approximately 30 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01685892 on ClinicalTrials.gov Archive Site
  • Percentage of Participants with Complete Response (CR) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Objective Response (OR) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Duration of OR [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) [ 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: Time to Maximum Concentration (Tmax) [ 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 ]
  • Safety: Percentage of Participants with Adverse Events (AEs) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Safety: Percentage of Participants with Clinically Significant Changes in Safety Measurements, Including Laboratory Tests and Vital Signs [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Safety: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Number of B-Cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Number of T-Cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Number of Natural Killer (NK) Cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Serum Immunoglobulin Level [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area Under the Concentration Time Curve (AUC) [ 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 ]
Not Provided
Not Provided
 
A Study of Venetoclax (GDC-0199; ABT-199) 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. All participants (relapsed/refractory and previously untreated) will receive 6 cycles of obinutuzumab and venetoclax. After completing combination treatment, previously untreated participants will receive single agent venetoclax for at least 6 additional months (the anticipated time on treatment for previously untreated participants is at least 12 months). After completing combination treatment, relapsed/refractory participants will continue single agent venetoclax until disease progression.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphocytic Leukemia, Chronic
  • Drug: Obinutuzumab
    100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
    Other Name: GA101; RO5072759
  • Drug: Venetoclax (GDC-0199; ABT-199)
    Multiple doses of venetoclax are administered orally once daily.
    Other Name: ABT-199; GDC-0199
  • Experimental: 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 obinutuzumab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax (GDC-0199; ABT-199)
  • Experimental: 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 obinutuzumab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax (GDC-0199; ABT-199)
  • Experimental: 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 obinutuzumab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax (GDC-0199; ABT-199)
  • Experimental: 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 obinutuzumab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
    Interventions:
    • Drug: Obinutuzumab
    • Drug: Venetoclax (GDC-0199; ABT-199)
  • Experimental: 5 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 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 (GDC-0199; ABT-199)
  • Experimental: 6 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 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 (GDC-0199; ABT-199)
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
81
May 2019
May 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 </=1
  • Adequate bone marrow function
  • Adequate coagulation, renal and hepatic function
  • Female patients must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test
  • All female patients not surgically sterile or postmenopausal (for at least 1 year) and non-vasectomized male patients must practice at least one method of birth control during study participation and for 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is later
  • For women who are not postmenopausal (>/= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer
  • Men must remain abstinent or use a condom plus an additional contraceptive method that together results in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab.

Exclusion Criteria:

  • Infection with human immunodeficiency virus, hepatitis B, or hepatitis C
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Investigational or anti-cancer therapy within 5 half-lives of first drug administration
  • History of significant renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   United Kingdom
 
NCT01685892
GP28331, 2012-002038-34
Not Provided
Not Provided
Not Provided
Genentech, Inc.
Genentech, Inc.
AbbVie (prior sponsor, Abbott)
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
August 2016

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