Overview

This trial is active, not recruiting.

Condition lymphocytic leukemia, chronic
Treatments chlorambucil, gdc-0199, obinutuzumab
Phase phase 3
Targets BCL-2, CD20
Sponsor Hoffmann-La Roche
Collaborator AbbVie
Start date December 2014
End date November 2018
Trial size 445 participants
Trial identifier NCT02242942, 2014-001810-24, BO25323

Summary

This open-label, multicenter, randomized Phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and GDC-0199 versus obinutuzumab + chlorambucil (GClb) in patients 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Non-randomized phase
gdc-0199 ABT-0199
GDC-0199, 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
obinutuzumab GA-101; gazyva
Obinutuzumab, intravenous (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
(Experimental)
Randomized phase
gdc-0199 ABT-0199
GDC-0199, 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
obinutuzumab GA-101; gazyva
Obinutuzumab, intravenous (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
(Experimental)
Randomized phase
chlorambucil
Chlorambucil, administered orally: 0.5 mg/kg at Day 1 and Day 15 for Cycle 1-12
obinutuzumab GA-101; gazyva
Obinutuzumab, intravenous (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

Primary Outcomes

Measure
Progression-free survival (PFS), defined as the time from randomization to the first occurrence of progression, relapse or death from any cause as assessed by the investigator using IWCLL criteria
time frame: Up to 5 years

Secondary Outcomes

Measure
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: Up to 5 years
Objective response rate ([ORR] defined as rate of a clinical response of complete response [CR], CR with incomplete bone marrow recovery [CRi] or partial response [PR]) as determined by the investigator, according to the IWCLL criteria
time frame: At the completion of treatment assessment, approximately 1 year
Minimal residual disease (MRD) response rate, as measured by allele-specific oligonucleotide polymerase chain reaction (ASO-PCR)
time frame: At the completion of treatment assessment, approximately 1 year
ORR at completion of combination treatment response assessment
time frame: Cycle 7 day 1 or 28 days after last IV infusion, approximately 6 months
MRD response rate, as measured by ASO-PCR at completion of combination treatment response assessment
time frame: Cycle 9 day 1 or 3 months after last IV infusion, approximately 9 months
Overall survival
time frame: Time between the date of randomization and the date of death due to any cause, up to approximately 5 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 5 years
Best response achieved (CR, CRi, PR, stable disease, or progressive disease)
time frame: Up to and including the assessment at completion of treatment assessment, 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 5 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 5 years
Incidence of 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 GDC-0199 or after 90 days after last dose of obinutuzumab, whichever is longer
Incidence of severe adverse events
time frame: Up to 5 years
Incidence of adverse events of special interest
time frame: Up to 2 years after last dose of study drug

Eligibility Criteria

Male or female participants at least 18 years old.

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) > 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 - Patients 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 - Patients 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 GDC-0199 or to any of the excipients - Pregnant women and nursing mothers - Positive test results for chronic HBV infection (defined as positive HBsAg serology) or positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing) - Patients 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 CYP3A4 inhibitors or inducers within 7 days prior to the first dose of study drug

Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.
Location data was received from the National Cancer Institute and was last updated in September 2016.