chronic lymphocytic leukemia MedDRA version: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Venetoclax (GDC-0199)
Product Code: RO553-7382/F01-01
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Venetoclax
Current Sponsor code: RO5537382
Other descriptive name: GDC-
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion 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) > 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 357
Exclusion criteria
Exclusion criteria: - Transformation of CLL to aggressive Non-Hodgkin's lymphoma (Richters transformation or pro-lymphocytic leukemia) - Known central nervous system involvement - Patients 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 - Patients with active infections requiring IV treatment (grade 3 or 4) within the last two months prior to enrollment - 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 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) - Received agents known to be strong and moderate CYP3A4 inhibitors or inducers within 7 days prior to the first dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine efficacy by investigator-assessed PFS of a combined regimen of obinutuzumab and Venetoclax compared with GClb in previously untreated patients with CLL who have coexisting medical conditions.;Secondary Objective: To determine efficacy as assessed by additional outcome measures, including PFS assessed by Independent Review Committee [IRC], overall response, complete response and Minimal residual disease (MRD) response rate as measured by allele-specific oligonucleotide polymerase chain reaction [ASO-PCR];Primary end point(s): 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;Timepoint(s) of evaluation of this end point: At baseline, day 1 of cycle 7 and 9, day 1 of cycle 4, day 28 after treatment completion or early termination, during follow up i.e. 3 months after treatment completion or early termination and then regularly until 5 years from last patient enrolled. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - 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 - 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 - Complete response rate (defined as rate of a clinical response of CR or CRi at the completion of treatment assessment, as determined by the investigator according to the IWCLL guidelines) - Minimal residual disease (MRD) response rate, as measured by allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) - ORR at completion of combination treatment response assessment - MRD response rate, as measured by ASO-PCR at completion of combination treatment response assessment - Overall survival - Duration of objective response - Best response achieved (CR, CRi, PR, stable disease, or progressive disease) - Event-free survival - Time to next anti-leukemic treatment - Incidence of adverse events assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 - Incidence of severe adverse events - Incidence of adverse events of special interest;Timepoint(s) of evaluation of this end point: Up to 5 years from last patient enrolled. | — |
Countries
Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Croatia, Czech Republic, Denmark, Egypt, Estonia, France, Germany, Italy, Mexico, New Zealand, Poland, Romania, Russian Federation, Slovakia, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed