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

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.
 
ClinicalTrials.gov Identifier: NCT01685892
Recruitment Status : Active, not recruiting
First Posted : September 14, 2012
Last Update Posted : November 19, 2019
Sponsor:
Collaborator:
AbbVie (prior sponsor, Abbott)
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE September 12, 2012
First Posted Date  ICMJE September 14, 2012
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE November 29, 2012
Actual Primary Completion Date May 21, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2017)
  • 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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
  • Maximum tolerated dose [ Time Frame: Approximately 30 months ]
  • Safety: incidence of adverse events [ Time Frame: approximately 30 months ]
Change History Complete list of historical versions of study NCT01685892 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2017)
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to end of study (up to approximately 5 years and 5 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 5 years and 5 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 5 years and 5 months) ]
  • Duration of Objective Response as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 5 years and 5 months) ]
  • Overall Survival [ Time Frame: Baseline up to death or end of study (up to approximately 5 years and 5 months) ]
  • Progression-Free Survival as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 5 years and 5 months) ]
  • Change from Baseline in Number of B-Cells [ Time Frame: Baseline up to end of study (up to approximately 5 years and 5 months) ]
  • Change from Baseline in Number of T-Cells [ Time Frame: Baseline up to end of study (up to approximately 5 years and 5 months) ]
  • Change from Baseline in Number of Natural Killer (NK) Cells [ Time Frame: Baseline up to end of study (up to approximately 5 years and 5 months) ]
  • Change from Baseline in Serum Immunoglobulin Level [ Time Frame: Baseline up to end of study (up to approximately 5 years and 5 months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2012)
Pharmacokinetics: Area under the concentration time curve [ Time Frame: Approximately 30 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Venetoclax in Combination With Obinutuzumab in Participants With Chronic Lymphocytic Leukemia
Official Title  ICMJE 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
Brief Summary This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics as well as the preliminary efficacy 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphocytic Leukemia, Chronic
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * Flinn IW, Gribben JG, Dyer MJS, Wierda W, Maris MB, Furman RR, Hillmen P, Rogers KA, Iyer SP, Quillet-Mary A, Ysebaert L, Walter HS, Verdugo M, Klein C, Huang H, Jiang Y, Lozanski G, Pignataro DS, Humphrey K, Mobasher M, Kipps TJ. Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Blood. 2019 Jun 27;133(26):2765-2775. doi: 10.1182/blood-2019-01-896290. Epub 2019 Mar 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 24, 2017)
82
Original Estimated Enrollment  ICMJE
 (submitted: September 12, 2012)
64
Estimated Study Completion Date  ICMJE December 31, 2019
Actual Primary Completion Date May 21, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01685892
Other Study ID Numbers  ICMJE GP28331
2012-002038-34 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE AbbVie (prior sponsor, Abbott)
Investigators  ICMJE
Study Director: Clinical Trials Genentech, Inc.
PRS Account Genentech, Inc.
Verification Date November 2019

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