A Study of Venetoclax (GDC-0199; ABT-199) 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: August 1, 2016
Last verified: August 2016
  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. All participants (relapsed/refractory and previously untreated) will receive 6 cycles of obinutuzumab and venetoclax. After completing combination treatment, previously untreated participants will receive single agent venetoclax for at least 6 additional months (the anticipated time on treatment for previously untreated participants is at least 12 months). After completing combination treatment, relapsed/refractory participants will continue single agent venetoclax until disease progression.

Condition Intervention Phase
Lymphocytic Leukemia, Chronic
Drug: Obinutuzumab
Drug: Venetoclax (GDC-0199; ABT-199)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with Complete Response (CR) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Objective Response (OR) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Duration of OR [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Progression-Free Survival (PFS) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Minimum Plasma Concentration (Cmin) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Time to Maximum Concentration (Tmax) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximal Plasma Concentration (Cmax) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Safety: Percentage of Participants with Adverse Events (AEs) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Safety: Percentage of Participants with Clinically Significant Changes in Safety Measurements, Including Laboratory Tests and Vital Signs [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Safety: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Number of B-Cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Number of T-Cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Number of Natural Killer (NK) Cells [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Change in Serum Immunoglobulin Level [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area Under the Concentration Time Curve (AUC) [ Time Frame: Approximately 30 months ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: November 2012
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Dose-Finding: Schedule A: Relapsed/Refractory CLL
In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
Drug: Obinutuzumab
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (GDC-0199; ABT-199)
Multiple doses of venetoclax are administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: 2 Dose-Finding: Schedule B: Relapsed/Refractory CLL
In 4 cohorts of participants with relapsed/refractory CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
Drug: Obinutuzumab
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (GDC-0199; ABT-199)
Multiple doses of venetoclax are administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: 3 Dose-Finding: Schedule A: Previously Untreated CLL
In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule A venetoclax (GDC-0199; ABT-199) will be introduced before obinutuzumab. Schedule A will be explored prior to Schedule B.
Drug: Obinutuzumab
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (GDC-0199; ABT-199)
Multiple doses of venetoclax are administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: 4 Dose-Finding: Schedule B: Previously Untreated CLL
In 4 cohorts of participants with previously untreated CLL escalating doses of venetoclax (GDC-0199; ABT-199) will be administered in combination with fixed dose obinutuzumab in the dose-finding stage. In Schedule B venetoclax (GDC-0199; ABT-199) will be introduced after obinutuzumab. Schedule A will be explored prior to Schedule B.
Drug: Obinutuzumab
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (GDC-0199; ABT-199)
Multiple doses of venetoclax are administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: 5 Safety Expansion: Relapsed/Refractory CLL
In participants with relapsed/refractory CLL a recommended dose of venetoclax (GDC-0199; ABT-199) 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
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (GDC-0199; ABT-199)
Multiple doses of venetoclax are administered orally once daily.
Other Name: ABT-199; GDC-0199
Experimental: 6 Safety Expansion: Previously Untreated CLL
In participants with previously untreated CLL a recommended dose of venetoclax (GDC-0199; ABT-199) 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
100 mg of obinutuzumab is administered by intravenous infusion on Day 1 of Cycle 1, 900 mg on Day 2 of Cycle 1, 1000 mg on Day 8 and 15 of Cycle 1 and 1000 mg on Day 1 of Cycles 2-6.
Other Name: GA101; RO5072759
Drug: Venetoclax (GDC-0199; ABT-199)
Multiple doses of venetoclax are administered orally once daily.
Other Name: ABT-199; GDC-0199

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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 </=1
  • Adequate bone marrow function
  • Adequate coagulation, renal and hepatic function
  • Female patients must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test
  • All female patients not surgically sterile or postmenopausal (for at least 1 year) and non-vasectomized male patients must practice at least one method of birth control during study participation and for 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is later
  • For women who are not postmenopausal (>/= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer
  • Men must remain abstinent or use a condom plus an additional contraceptive method that together results in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab.

Exclusion Criteria:

  • Infection with human immunodeficiency virus, hepatitis B, or hepatitis C
  • Uncontrolled autoimmune hemolytic anemia or thrombocytopenia
  • Investigational or anti-cancer therapy within 5 half-lives of first drug administration
  • 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
La Jolla, California, United States, 92093
United States, Colorado
Denver, Colorado, United States, 80218
United States, Florida
Sarasota, Florida, United States, 34232
United States, New York
Buffalo, New York, United States, 14263
New York, New York, United States, 10065
United States, Ohio
Columbus, Ohio, United States, 43210
United States, Oregon
Springfield, Oregon, United States, 97477
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Houston, Texas, United States, 77030
United States, West Virginia
Morgantown, West Virginia, United States, 26506
United Kingdom
Leeds, United Kingdom, LS9 7TF
Leicester, United Kingdom, LE1 5WW
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 
Study First Received: September 12, 2012
Last Updated: August 1, 2016
Health Authority: United States: Food and Drug Administration

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 August 30, 2016