A Study of Venetoclax in Combination With Bendamustine + Rituximab or Bendamustine + Obinutuzumab in Participants With Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia (CLL)

NCT ID: NCT01671904

Last Updated: 2020-10-14

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

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-13

Study Completion Date

2020-08-11

Brief Summary

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This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics of venetoclax (GDC-0199, ABT-199) administered in combination with bendamustine and rituximab (BR) (MabThera/Rituxan) or bendamustine and obinutuzumab (BG) to participants with first-line (1L)/previously untreated or relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). The study will explore two venetoclax combination regimens in participants with 1L CLL: BR+venetolax (V) and BG+V. Participants with R/R CLL will be administered BR+V.

Detailed Description

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Conditions

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Chronic Lymphocytic Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1L CLL BR+V

Participants with first-line (1L)/previously untreated CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and rituximab (BR). Participants received six 28-day cycles of BR+V. Participants with 1L CLL received 6 months of single-agent venetoclax for a total of 1-year treatment duration. Single-agent venetoclax could be extended if there was detectable minimal residual disease (MRD) in the bone marrow and/or partial response (PR) after 1 year of treatment and upon the request of the treating physician.

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter \[mg/m\^2\]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.

Rituximab

Intervention Type DRUG

Participants will receive IV infusion of rituximab (375 mg/m\^2) on Day 1 of Cycle 1 and 500 mg/m\^2 administered on Day 1 of Cycles 2-6.

Venetoclax

Intervention Type DRUG

Participants will receive multiple doses of venetoclax orally once daily.

1L CLL BG+V

Participants with first-line (1L)/previously untreated CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and obinutuzumab (BG). Participants received six 28-day cycles of BG+V. Participants with 1L CLL received 6 months of single-agent venetoclax for a total of 1-year treatment duration. Single-agent venetoclax could be extended if there was detectable minimal residual disease (MRD) in the bone marrow and/or partial response (PR) after 1 year of treatment and upon the request of the treating physician.

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter \[mg/m\^2\]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.

Obinutuzumab

Intervention Type DRUG

Participants will receive IV infusion of obinutuzumab (100 milligrams \[mg\]) on Day 1 of Cycle 1; 900 mg administered on Day 2 of Cycle 1; and 1000 mg administered 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.

R/R CLL BR+V

Participants with relapsed/refractory (R/R) CLL were administered escalating doses of venetoclax (V) in combination with fixed dose bendamustine and rituximab (BR). Participants received six 28-day cycles of BR+V. Participants with R/R CLL continued single-agent venetoclax until disease progression, death, or unacceptable toxicity.

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter \[mg/m\^2\]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.

Rituximab

Intervention Type DRUG

Participants will receive IV infusion of rituximab (375 mg/m\^2) on Day 1 of Cycle 1 and 500 mg/m\^2 administered 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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Bendamustine

Participants will receive intravenous (IV) infusion of bendamustine (90 or 70 milligrams per square meter \[mg/m\^2\]) on Days 2-3 of Cycle 1 and Days 1-2 of Cycles 2-6.

Intervention Type DRUG

Obinutuzumab

Participants will receive IV infusion of obinutuzumab (100 milligrams \[mg\]) on Day 1 of Cycle 1; 900 mg administered on Day 2 of Cycle 1; and 1000 mg administered on Days 8 and 15 of Cycle 1 and on Day 1 of Cycles 2-6.

Intervention Type DRUG

Rituximab

Participants will receive IV infusion of rituximab (375 mg/m\^2) on Day 1 of Cycle 1 and 500 mg/m\^2 administered 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 MabThera; Rituxan ABT-199; GDC-0199

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of relapsing/refractory or previously untreated CLL
* Eastern Cooperative Oncology Group (ECOG) performance score of less than equal to (\</=) 1
* Adequate bone marrow function
* Adequate coagulation, renal and hepatic function
* Hematological values within the limits independent of growth factor support or transfusion unless cytopenia is caused by the underlying disease, i.e., no evidence of additional bone marrow dysfunction (e.g., myelodysplastic syndrome, hypoplastic bone marrow)

Exclusion Criteria

* Participants received an allogeneic stem cell transplant
* Known human immunodeficiency virus (HIV) positivity
* Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
* Positive test results for chronic hepatitis B infection and hepatitis C virus (HCV)
* Received any anti-cancer therapy including chemotherapy or radiotherapy, steroid therapy for anti-neoplastic intent, and investigational therapy, including targeted small molecule agents within 28 days prior to the first dose of study drug or has not recovered to less than Grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy
* Significant history of 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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University of California San Diego Medical Center

La Jolla, California, United States

Site Status

Ingalls Hospital; Cancer Clinical Trials

Harvey, Illinois, United States

Site Status

Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

North Star Lodge

Yakima, Washington, United States

Site Status

Hopital Claude Huriez

Lille, , France

Site Status

Hopital Saint Eloi

Montpellier, , France

Site Status

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Universitatsklinik Koln

Cologne, , Germany

Site Status

Apotheke des Universitätsklinikums Freiburg

Freiburg im Breisgau, , Germany

Site Status

Klinikum Schwabing

München, , Germany

Site Status

Universtitätsklinikum Ulm; Klinik für Innere Medizin III

Ulm, , Germany

Site Status

Countries

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United States France Germany

Other Identifiers

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2012-002351-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO28440

Identifier Type: -

Identifier Source: org_study_id

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