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

NCT ID: NCT01685892

Last Updated: 2020-01-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-11-29

Study Completion Date

2019-08-23

Brief Summary

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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

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Conditions

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Lymphocytic Leukemia, Chronic

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

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.

Venetoclax

Intervention Type DRUG

Participants will receive multiple doses of venetoclax orally once daily.

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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

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.

Venetoclax

Intervention Type DRUG

Participants will receive multiple doses of venetoclax orally once daily.

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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

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.

Venetoclax

Intervention Type DRUG

Participants will receive multiple doses of venetoclax orally once daily.

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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

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.

Venetoclax

Intervention Type DRUG

Participants will receive multiple doses of venetoclax orally once daily.

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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

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.

Venetoclax

Intervention Type DRUG

Participants will receive multiple doses of venetoclax orally once daily.

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.

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

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.

Venetoclax

Intervention Type DRUG

Participants will receive multiple doses of venetoclax orally once daily.

Interventions

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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.

Intervention Type DRUG

Venetoclax

Participants will receive multiple doses of venetoclax orally once daily.

Intervention Type DRUG

Other Intervention Names

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GA101; RO5072759 ABT-199, GDC-0199

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie (prior sponsor, Abbott)

INDUSTRY

Sponsor Role collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Genentech, Inc.

Locations

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UCSD Moores Cancer Center

La Jolla, California, United States

Site Status

Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center

Denver, Colorado, United States

Site Status

Weill Cornell Medical College-New York Presbyterian Hospital

New York, New York, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Oncology Associates of Oregon

Springfield, Oregon, United States

Site Status

SCRI-Tennessee Oncology

Nashville, Tennessee, United States

Site Status

The Methodist Hospital Research Institute; Academic Office of Clinical Trials

Houston, Texas, United States

Site Status

St James University Hospital

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary NHS Trust

Leicester, , United Kingdom

Site Status

Barts and The London School of Medicine and Dentistry; Queen Mary, University of London

London, , United Kingdom

Site Status

Countries

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United States United Kingdom

References

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Samineni D, Gibiansky L, Wang B, Vadhavkar S, Rajwanshi R, Tandon M, Sinha A, Al-Sawaf O, Fischer K, Hallek M, Salem AH, Li C, Miles D. Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Adv Ther. 2022 Aug;39(8):3635-3653. doi: 10.1007/s12325-022-02170-w. Epub 2022 Jun 16.

Reference Type DERIVED
PMID: 35708885 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30862645 (View on PubMed)

Other Identifiers

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2012-002038-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GP28331

Identifier Type: -

Identifier Source: org_study_id

NCT02339181

Identifier Type: -

Identifier Source: nct_alias

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