The purpose of this study is to determine the proportion of participants who achieve undetectable measurable residual disease (uMRD) in previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
This is a multicenter phase II study evaluating zanubrutinib, obinutuzumab, and sonrotoclax in previously untreated patients with CLL or SLL. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved sonrotoclax as a treatment for any disease. The U.S. Food and Drug Administration (FDA) has approved zanubrutinib and obinutuzumab as a treatment option for your disease. The combination of zanubrutinib, obinutuzumab, and sonrotoclax (BOSon regimen) is not an approved regimen for CLL or SLL and is investigational in this study. The duration of the protocol therapy will depend on participant's individual response, with a longer course of therapy for participants with a lower response, and a shorter course of therapy for those with a faster response. After removal from the protocol therapy, participants will be followed for up to 2 years after the final patient is enrolled. It is expected that about 40 people will take part in this research study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Bruton's Tyrosine Kinase (BTK) inhibitor
B-cell lymphoma 2 (BCL2) protein inhibitor
Anti-CD20 monoclonal antibody
Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
NOT_YET_RECRUITINGRate of Undetectable MRD (uMRD) at Best Response
The proportion of patients achieving undetectable MRD in peripheral blood using the ClonoSEQ assay (cutoff, \<10-5). The number of responses will be reported with a proportion with 95% exact binomial confidence interval.
Time frame: Day 1 to 2 years after final patient enrolled
Proportion of Participants with Tumor Lysis Syndrome (TLS) Laboratory Abnormalities Requiring Intervention
The proportion of participants who have 1 or more TLS laboratory abnormalities requiring intervention on a ramp-up date with normal pre-dose TLS parameters and ALC \<25,000/µl during the sonrotoclax ramp-up. The number of responses will be reported with a proportion with 95% exact binomial confidence interval.
Time frame: Day 1 to completion date of sonrotoclax ramp-up
Frequency of uMRD at Best Response
The proportion of patients achieving uMRD in both peripheral blood (PB) and bone marrow (BM) by ClonoSEQ (cutoff, \<10-5).
Time frame: Day 1 to 2 years after final patient enrolled
Rate of uMRD after 10 and 24 cycles
The proportion of patients achieving uMRD in both PB and BM by ClonoSEQ (cutoff, \<10-5) after 10 and 24 cycles.
Time frame: Day 1 to end of 10 cycles and end of 24 cycles
Rate of Complete Response (CR) or CR with Incomplete Marrow Recovery (CRi), or Partial Response (PR)
Patients will have their response classified per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.
Time frame: Day 1 to 2 years after final patient enrolled
Progression-free survival (PFS), Overall Survival (OS), MRD4-Free Survival, and MRD5-free survival
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
PFS is the time from treatment start to the earlier of progression or death due to any cause. OS is the time from treatment start to death due to any cause. MRD4-Free Survival is the time from treatment start to the earlier of detectable MRD ≥10-4 by immunosequencing (Adaptive ClonoSEQ assay), progression, or death due to any cause. MRD5-Free Survival the time from treatment start to the earlier of detectable MRD ≥10-5 by immunosequencing (Adaptive ClonoSEQ assay), progression, or death due to any cause. Time-to-event endpoints will be evaluated using the Kaplan-Meier method. Survival distributions may be described as medians or 1- and 2-year probabilities with 95% confidence intervals. Uni- and multi-variable Cox regressions may also be performed and will be summarized with hazard ratios, 95% confidence intervals, and Wald p-values.
Time frame: Day 1 to first documented disease progression or date of death from any cause, assessed for 2 year after final patient enrolled
Proportion of Participants Without TLS-related Laboratories Requiring Clinical Intervention
TLS is defined according to Howard criteria. The nature, frequency, severity, and timing of TLS will be tabulated and summarized descriptively.
Time frame: Day 1 to end of Cycle 3 (each cycle is 28 days)
Distribution of TLS Risk
TLS is defined according to Howard criteria. The nature, frequency, severity, and timing of TLS will be tabulated and summarized descriptively.
Time frame: Day 1 to end of Cycle 2 (each cycle is 28 days)
Incidence and Severity of Treatment-Emergent Adverse Events
Patients will have their toxicities graded and reported at every visit according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The nature, frequency, severity, and timing of adverse events will be tabulated and summarized descriptively. The safety analyses will include all participants who received at least one dose of study treatment.
Time frame: Day 1 to 2 years after final patient enrolled