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A Study to Compare the Efficacy and Safety of Obinutuzumab + Venetoclax (GDC-0199) Versus Obinutuzumab + Chlorambucil in Participants With Chronic Lymphocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
AbbVie
German CLL Study Group
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02242942
First received: September 16, 2014
Last updated: February 14, 2017
Last verified: February 2017
  Purpose
This open-label, multicenter, randomized Phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax versus obinutuzumab + chlorambucil in participants with chronic lymphocytic leukemia (CLL) and coexisting medical conditions. The anticipated time on study treatment will be approximately one year and the follow-up period will be up to 5 years.

Condition Intervention Phase
Lymphocytic Leukemia, Chronic
Drug: Chlorambucil
Drug: Venetoclax
Drug: Obinutuzumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Prospective, Open-Label, Multicenter Randomized Phase III Trial to Compare The Efficacy and Safety of A Combined Regimen of Obinutuzumab and Venetoclax (GDC-0199/ABT-199) Versus Obinutuzumab and Chlorambucil in Previously Untreated Patients With CLL and Coexisting Medical Conditions

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) Based on Investigator Assessment (Using IWCLL Criteria), Defined as the Time From Randomization to the First Occurrence of Progression, Relapse or Death From Any Cause [ Time Frame: Baseline until disease progression or death (up to approximately 7 years) ]

Secondary Outcome Measures:
  • PFS Based on Institutional Review Committee (IRC)-Assessments, Defined as the Time From Randomization to the First Occurrence of Progression or Relapse or Death From any Cause [ Time Frame: Baseline until disease progression or death (up to approximately 7 years) ]
  • Percentage of Participants with an Overall Response of Complete Response (CR), CR with Incomplete Bone marrow Recovery (CRi), or Partial Response (PR), as Determined by the Investigator at Completion of Treatment According to IWCLL Criteria [ Time Frame: Baseline up to within 3 months of last day of treatment, approximately 1 year ]
  • Percentage of Participants With Minimal Residual Disease (MRD) Negativity as Measured by Allele-Specific Oligonucleotide Polymerase Chain Reaction (ASO-PCR) at Completion of Treatment [ Time Frame: Baseline up to within 3 months of last day of treatment, approximately 1 year ]
  • Percentage of Participants With OR at Completion of Combination Treatment Response Assessment [ Time Frame: Day 1 Cycle 7 or 28 days after last IV infusion, approximately 6 months ]
  • Percentage of Participants With MRD Negativity, as Measured by ASO-PCR at Completion of Combination Treatment Response Assessment [ Time Frame: Day 1 Cycle 9 or 3 months after last IV infusion, approximately 9 months ]
  • Overall Survival [ Time Frame: Baseline until death (up to approximately 7 years) ]
  • Duration of Objective Response [ Time Frame: Time from the first occurrence of a documented objective response to the time of progressive disease as determined by the investigator or death from any cause, up to approximately 7 years ]
  • Percentage of Participants By Best Response Achieved (CR, CRi, PR, Stable Disease, or Progressive Disease) [ Time Frame: Baseline up to within 3 months of last day of treatment, approximately 1 year ]
  • Event-Free Survival [ Time Frame: Time between date of randomization and the date of disease progression/relapse on the basis of investigator-assessment, death, or start of a new anti-leukemic therapy, up to 7 years ]
  • Time to Next Anti-Leukemic Treatment [ Time Frame: Time between the date of randomization and the date of first intake of new anti-leukemic therapy, up to 7 years ]
  • Percentage of Participants With Adverse Events Assessed According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 [ Time Frame: 28 days after the last dose of venetoclax or after 90 days after last dose (up to 13 months) ]
  • Percentage of Participants With Human-Anti-Human Antibodies [ Time Frame: Baseline up to approximately 7 years ]
  • Percentage of Participants With Adverse Events of Special Interest [ Time Frame: Baseline up to approximately 7 years ]
  • Apparent Clearance of Obinutuzumab [ Time Frame: Pre-obinutuzumab infusion (0 hour) and end of obinutuzumab infusion (duration of infusion: 25 - 400 milligrams per hour [mg/hr]) on Day 1 Cycle 4 ]
  • Apparent Clearance of Venetoclax [ Time Frame: Pre-venetoclax dose (0 hour) and 4 hours post- venetoclax dose on Day 1 Cycle 4 ]
  • Apparent Volume of Distribution of Obinutuzumab [ Time Frame: Pre-obinutuzumab infusion (0 hour) and end of obinutuzumab infusion (duration of infusion: 25 - 400 mg/hr) on Day 1 Cycle 4 ]
  • Apparent Volume of Distribution of Venetoclax [ Time Frame: Pre-venetoclax dose (0 hour) and 4 hours post- venetoclax dose on Day 1 Cycle 4 ]
  • Number of CD19 + CD5+ Cells [ Time Frame: Baseline up to 7 years ]
  • Number of CD19 + CD5- Cells [ Time Frame: Baseline up to 7 years ]
  • Change From Baseline in M.D. Anderson Symptom Inventory (MDASI) score [ Time Frame: Baseline up to 28 days after last dose, approximately 1 year ]
  • Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30) [ Time Frame: Baseline up to 28 days after last dose, approximately 1 year ]
  • Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D-3L) [ Time Frame: Baseline up to 28 days after last dose, approximately 1 year ]

Enrollment: 445
Study Start Date: December 2014
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Obinutuzumab + Chlorambucil
Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.
Drug: Chlorambucil
Chlorambucil 0.5 milligrams per kilogram (mg/kg) orally at Day 1 and Day 15 at of each 28 day cycle for 12 cycles.
Drug: Obinutuzumab
Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6
Other Name: GA-101; Gazyva
Experimental: Obinutuzumab + Venetoclax
Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Drug: Venetoclax
Venetoclax, oral tablet: 20 mg daily during Cycle 1, Day 22-28; 50 mg daily during Cycle 2, Day 1-7; 100 mg daily during Cycle 2, Day 8-14; 200 mg daily during Cycle 2, Day 15-21; 400 mg daily during Cycle 2, Day 22-28 and on Day 1-28 for all subsequent cycles until the end of Cycle 12.
Other Name: ABT-0199, GDC-0199
Drug: Obinutuzumab
Obinutuzumab, IV infusion: 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6
Other Name: GA-101; Gazyva

  Eligibility

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

Inclusion Criteria:

  • Documented previously untreated CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
  • CLL requiring treatment according to IWCLL criteria
  • Total Cumulative Illness Rating Scale (CIRS score) greater than (>) 6
  • Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as per protocol, unless cytopenia is due to marrow involvement of CLL
  • Adequate liver function
  • Life expectancy > 6 months
  • Agreement to use highly effective contraceptive methods per protocol

Exclusion Criteria:

  • Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richter's transformation or pro-lymphocytic leukemia)
  • Known central nervous system involvement
  • Participants with a history of confirmed progressive multifocal leukoencephalopathy (PML)
  • An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the treatment regimen of this trial with the exception of eyes, ears, nose, throat organ system
  • Participants with uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
  • Inadequate renal function
  • History of prior malignancy, except for conditions as listed in the protocol if patients have recovered from the acute side effects incurred as a result of previous therapy
  • Use of investigational agents or concurrent anti-cancer treatment within the last 4 weeks of registration
  • Participants with active bacterial, viral, or fungal infection requiring systemic treatment within the last two months prior to registration
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
  • Hypersensitivity to chlorambucil, obinutuzumab, or venetoclax or to any of the excipients
  • Pregnant women and nursing mothers
  • Positive test results for chronic hepatitis B virus (HBV) infection (defined as positive hepatitis B surface antigen [HBsAg] serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
  • Participants with known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus-1 (HTLV-1)
  • Requires the use of warfarin, marcumar, or phenprocoumon
  • Received agents known to be strong and moderate Cytochrome P450 3A inhibitors or inducers within 7 days prior to the first dose of study drug
  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: NCT02242942

  Show 196 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
AbbVie
German CLL Study Group
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02242942     History of Changes
Other Study ID Numbers: BO25323
2014-001810-24 ( EudraCT Number )
CLL14
Study First Received: September 16, 2014
Last Updated: February 14, 2017

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
Chlorambucil
Obinutuzumab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on March 24, 2017