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

Lymphocytic Leukemia, Chronic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01685892
• Other study ID #: GP28331
• Secondary ID: 2012-002038-34
• Status: Completed
• Phase: Phase 1
• Start date: November 29, 2012
• Est. completion date: August 23, 2019

Study information

• Verified date: January 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Other known NCT identifiers

• NCT02339181

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: August 23, 2019
• Est. primary completion date: May 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphocytic Leukemia, Chronic

Intervention

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.
• Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.

Locations

Country	Name	City	State
United Kingdom	St James University Hospital	Leeds
United Kingdom	Leicester Royal Infirmary NHS Trust	Leicester
United Kingdom	Barts and The London School of Medicine and Dentistry; Queen Mary, University of London	London
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center	Denver	Colorado
United States	The Methodist Hospital Research Institute; Academic Office of Clinical Trials	Houston	Texas
United States	UCSD Moores Cancer Center	La Jolla	California
United States	SCRI-Tennessee Oncology	Nashville	Tennessee
United States	Weill Cornell Medical College-New York Presbyterian Hospital	New York	New York
United States	Oncology Associates of Oregon	Springfield	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose Limiting Toxicities (DLTs)		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)
Primary	Maximum Tolerated Dose (MTD) of Venetoclax in Combination with Obinutuzumab		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	Percentage of Participants with Adverse Events		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab		Baseline up to Cycle 6 (1 Cycle=28 days)
Secondary	Area Under the Concentration-Time Curve (AUC) of Venetoclax		Baseline up to Cycle 6 (1 Cycle=28 days)
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax		Baseline up to Cycle 6 (1 Cycle=28 days)
Secondary	Maximal Plasma Concentration (Cmax) of Venetoclax		Baseline up to Cycle 6 (1 Cycle=28 days)
Secondary	Minimum Plasma Concentration (Cmin) of Venetoclax		Baseline up to Cycle 6 (1 Cycle=28 days)
Secondary	Cmax of Obinutuzumab		Baseline up to Cycle 6 (1 Cycle=28 days)
Secondary	Cmin of Obinutuzumab		Baseline up to Cycle 6 (1 Cycle=28 days)
Secondary	Percentage of Participants with Confirmed Complete Response (CR) as Determined by Standard CLL Response Criteria		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Percentage of Participants with Objective Response (Partial Response [PR] or CR [Including Cytopenic CR] as Determined by Standard CLL Response Criteria		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Duration of Objective Response as Determined by Standard CLL Response Criteria		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Overall Survival		Baseline up to death or end of study (up to approximately 5 years and 5 months)
Secondary	Progression-Free Survival as Determined by Standard CLL Response Criteria		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Change from Baseline in Number of B-Cells		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Change from Baseline in Number of T-Cells		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Change from Baseline in Number of Natural Killer (NK) Cells		Baseline up to end of study (up to approximately 5 years and 5 months)
Secondary	Change from Baseline in Serum Immunoglobulin Level		Baseline up to end of study (up to approximately 5 years and 5 months)