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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
82

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Genentech, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 29, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 21, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 23, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 12, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 12, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 14, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 10, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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