This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.
Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. Participants must have been diagnosed within 18 months prior to registration
Participants must have CLL-International Prognostic Index (CLL-IPI) score >= 4 and/or complex cytogenetics (defined as 3+ chromosomal abnormalities)
Cytogenetic AND/OR FISH analyses must be completed at a Clinical Laboratory Improvement Act (CLIA)-approved (or laboratories accredited under Accreditation Canada Diagnostics to conduct FISH analyses) laboratory within 18 months prior to registration. At minimum, FISH panel should use probes to detect for abnormalities in chromosomes 13q, 12, 11q, and 17p
TP53 gene mutation analysis performed at any CLIA-approved (or laboratories accredited under Accreditation Canada Diagnostics) lab (if completed) must be obtained within 18 months prior to registration. This sequencing test is distinct from FISH studies for del(17p)
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Computed Tomography
Procedure/SurgeryUndergo CT
Obinutuzumab
Biological/VaccineGiven IV
Questionnaire Administration
Other interventionAncillary studies
Venetoclax
DrugGiven PO
Overall survival (OS)
The final analysis will use stratified Cox proportional hazards regression stratified by Chronic Lymphocytic Leukemia \[CLL\] International Prognostic Indicator Risk score status (high risk versus very high risk) with a two-sided alpha of 0.05. The final analysis will occur after 58 OS events have been observed, or at 4 years after accrual completes, whichever occurs first. Under the alternative hypothesis, the final analysis is expected to occur at approximately 7.9 years after study activation (about 3.8 years after accrual completes).
Functional Assessment of Cancer Therapy (FACT)-Leukemia total score
A single comparison in the FACT-Leukemia total scores between patients randomized to early V-O versus delayed V-O will be conducted at the alpha=.05 level. The analysis of the 2-year FACT-Leukemia Total score will be conducted using multiple linear regression analysis, adjusting for stratification factor and the baseline FACT-Leukemia Total score as covariates. Will also conduct longitudinal modeling of the outcome measures over time.
Incidence of adverse events
Will utilize the National Cancer Institute Common Terminology Criteria for Adverse Events) version 5.0 for toxicity and adverse event reporting.
Overall Response rate
Will be compared using Fisher's exact test.
Progression free survival
Will be estimated using the Kaplan-Meier method and will be compared using log-rank tests and Cox regression models.
Event free survival
Will be estimated using the Kaplan-Meier method and will be compared using log-rank tests and Cox regression models.
FACT-Leukemia total score
Will include linear regression analyses by arm.
The individual components of the FACT-Leukemia
Will include physical, social, emotional, and functional well-being. Will include linear regression analyses by arm.
Patient-reported health-related quality of life
Will use simple descriptive statistics (means, medians, standard deviations, ranges) to describe patient-reported health related quality of life using the FACT-Leukemia and its individual domains between randomized arms. To assess potential trends, P-values using t-tests will be provided.
Click on the lead sponsor to view all of their trials.
