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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AbbVie (prior sponsor, Abbott)
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01685892
First received: September 12, 2012
Last updated: June 27, 2017
Last verified: June 2017
  Purpose
This multi-center, open-label, dose-finding study will evaluate the safety and pharmacokinetics 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).

Condition Intervention Phase
Lymphocytic Leukemia, Chronic Drug: Obinutuzumab Drug: Venetoclax Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • 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) ]
  • 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) ]

Secondary Outcome Measures:
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab [ Time Frame: 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) ]
  • Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax [ Time Frame: 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) ]
  • Minimum Plasma Concentration (Cmin) of Venetoclax [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Cmax of Obinutuzumab [ Time Frame: Baseline up to Cycle 6 (1 Cycle=28 days) ]
  • Cmin of Obinutuzumab [ Time Frame: 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 6 years 4 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 6 years 4 months) ]
  • Duration of Objective Response as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Overall Survival [ Time Frame: Baseline up to death or end of study (up to approximately 6 years 4 months) ]
  • Progression-Free Survival as Determined by Standard CLL Response Criteria [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Number of B-Cells [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Number of T-Cells [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Number of Natural Killer (NK) Cells [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]
  • Change from Baseline in Serum Immunoglobulin Level [ Time Frame: Baseline up to end of study (up to approximately 6 years 4 months) ]

Enrollment: 82
Actual Study Start Date: November 29, 2012
Estimated Study Completion Date: April 2, 2019
Estimated Primary Completion Date: April 2, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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 Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199, GDC-0199
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: 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 Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199, GDC-0199
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: 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 Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199, GDC-0199
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: 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 Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199, GDC-0199
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: 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 Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199, GDC-0199
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: 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 Name: GA101; RO5072759
Drug: Venetoclax
Participants will receive multiple doses of venetoclax orally once daily.
Other Name: ABT-199, GDC-0199

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01685892

Locations
United States, California
UCSD Moores Cancer Center
La Jolla, California, United States, 92093
United States, Colorado
Colorado Blood Cancer Institute (CBCI) at Presbyterian/ St. Luke's Medical Center
Denver, Colorado, United States, 80218
United States, Florida
Florida Cancer Specialists; Sarasota
Sarasota, Florida, United States, 34232
United States, New York
Roswell Park Cancer Inst.
Buffalo, New York, United States, 14263
Weill Cornell Medical College-New York Presbyterian Hospital
New York, New York, United States, 10021
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Oregon
Oncology Associates of Oregon
Springfield, Oregon, United States, 97477
United States, Tennessee
SCRI-Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
M.D Anderson Cancer Center
Houston, Texas, United States, 77030
The Methodist Hospital Research Institute; Academic Office of Clinical Trials
Houston, Texas, United States, 77030
United States, West Virginia
Mary Babb Randolph Cancer Center
Morgantown, West Virginia, United States, 26506
United Kingdom
St James University Hospital
Leeds, United Kingdom, LS9 7TF
Leicester Royal Infirmary NHS Trust
Leicester, United Kingdom, LE1 5WW
Barts and The London School of Medicine and Dentistry; Queen Mary, University of London
London, United Kingdom, E1 2AD
Sponsors and Collaborators
Genentech, Inc.
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01685892     History of Changes
Obsolete Identifiers: NCT02339181
Other Study ID Numbers: GP28331
2012-002038-34 ( EudraCT Number )
Study First Received: September 12, 2012
Last Updated: June 27, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Obinutuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 25, 2017