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

January 7, 2020 updated by: Genentech, Inc.

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 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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Leeds, United Kingdom, LS9 7TF
        • St James University Hospital
      • Leicester, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary NHS Trust
      • London, United Kingdom, E1 2AD
        • Barts and The London School of Medicine and Dentistry; Queen Mary, University of London
  • United States
    • California
      • La Jolla, California, United States, 92093
        • UCSD Moores Cancer Center
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
    • New York
      • New York, New York, United States, 10021
        • Weill Cornell Medical College-New York Presbyterian Hospital
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
    • Oregon
      • Springfield, Oregon, United States, 97477
        • Oncology Associates of Oregon
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • SCRI-Tennessee Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital Research Institute; Academic Office of Clinical Trials

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Names:
  • ABT-199, GDC-0199
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 Names:
  • GA101; RO5072759
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.
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Names:
  • ABT-199, GDC-0199
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 Names:
  • GA101; RO5072759
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.
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Names:
  • ABT-199, GDC-0199
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 Names:
  • GA101; RO5072759
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.
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Names:
  • ABT-199, GDC-0199
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 Names:
  • GA101; RO5072759
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.
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Names:
  • ABT-199, GDC-0199
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 Names:
  • GA101; RO5072759
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.
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Names:
  • ABT-199, GDC-0199
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 Names:
  • GA101; RO5072759

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
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)
Sch A (Cycle 1 Day 1 to Day 21), Sch B (Cycle 1 Day 22 to Cycle 2 Day 28) (1 Cycle=28 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Percentage of Participants with Adverse Events
Time Frame: Baseline up to end of study (up to approximately 5 years and 5 months)
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)
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)
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)
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)
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)
Baseline up to Cycle 6 (1 Cycle=28 days)
Cmax of Obinutuzumab
Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days)
Baseline up to Cycle 6 (1 Cycle=28 days)
Cmin of Obinutuzumab
Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Baseline up to end of study (up to approximately 5 years and 5 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genentech, Inc.

Collaborators

AbbVie (prior sponsor, Abbott)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 29, 2012

Primary Completion (Actual)

May 21, 2018

Study Completion (Actual)

August 23, 2019

Study Registration Dates

First Submitted

September 12, 2012

First Submitted That Met QC Criteria

September 12, 2012

First Posted (Estimate)

September 14, 2012

Study Record Updates

Last Update Posted (Actual)

January 10, 2020

Last Update Submitted That Met QC Criteria

January 7, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GP28331
  • 2012-002038-34 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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