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NCT Number: NCT01685892

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

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).

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Key information

Conditions

Lymphocytic Leukemia, Chronic Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, B-Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

St James University Hospital, Leeds, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Obinutuzumab

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.

Other names: GA101; RO5072759

Venetoclax

Drug

Participants will receive multiple doses of venetoclax orally once daily.

Other names: ABT-199, GDC-0199

Primary outcomes

  1. 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)

  2. 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 outcomes

  1. Percentage of Participants with Adverse Events

    Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

  2. Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Obinutuzumab

    Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

  3. Area Under the Concentration-Time Curve (AUC) of Venetoclax

    Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

  4. Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax

    Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

  5. Maximal Plasma Concentration (Cmax) of Venetoclax

    Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

  6. Minimum Plasma Concentration (Cmin) of Venetoclax

    Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

  7. Cmax of Obinutuzumab

    Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

  8. Cmin of Obinutuzumab

    Time frame: Baseline up to Cycle 6 (1 Cycle=28 days)

  9. 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 5 years and 5 months)

  10. 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 5 years and 5 months)

  11. Duration of Objective Response as Determined by Standard CLL Response Criteria

    Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

  12. Overall Survival

    Time frame: Baseline up to death or end of study (up to approximately 5 years and 5 months)

  13. Progression-Free Survival as Determined by Standard CLL Response Criteria

    Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

  14. Change from Baseline in Number of B-Cells

    Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

  15. Change from Baseline in Number of T-Cells

    Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

  16. Change from Baseline in Number of Natural Killer (NK) Cells

    Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

  17. Change from Baseline in Serum Immunoglobulin Level

    Time frame: Baseline up to end of study (up to approximately 5 years and 5 months)

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Collaborators

  • AbbVie (prior sponsor, Abbott)

Registry information

Official study 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

Important dates

Study start
2012
Primary completion
2018
Study completion
2019
First posted
Sep 14, 2012
Registry last updated
Jan 10, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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