Zanubrutinib, Obinutuzumab, Sonrotoclax (BOSon) or BGB-16673, Obinutuzumab, Sonrotoclax (DOSon) in TN CLL/SLL
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMassachusetts General Hospital
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participant must have CLL or SLL (WHO criteria).
Participant must require treatment according to iwCLL guidelines.
Prior local radiation for symptomatic disease is permitted.
Short course systemic corticosteroids is permissible for disease control, improvement of performance status, or non-cancer indication. However, duration of steroid course must be ≤14 days with maximum daily dose of ≤100 mg prednisone, ≤20 mg dexamethasone, or equivalent, and must be discontinued prior to study treatment (last dose may be administered up until the morning of / prior to study treatment). Inhaled steroids, topical steroids, and replacement / stress corticosteroids are permitted independent of above rules. In cases of autoimmune complications of CLL (e.g., ITP or AIHA), steroid usage is permitted.
Disqualifiers
Known histologic transformation from CLL or SLL to an aggressive lymphoma (i.e., Richter's transformation).
Known central nervous system involvement with CLL or SLL.
Other diagnosis of active malignancy or systemic therapy within 2 years of study treatment. Note: An active malignancy or systemic therapy within 2 years for another malignancy, whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Also, local/regional therapy with curative intent such as surgical resection or localized radiation at any timepoint is permitted.
Any uncontrolled illness that in the opinion of the investigator would preclude administration of study therapy (e.g., significant active infections, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction).
Trial design
Design model
Sequential
Treatments tested in this trial
Zanubrutinib
DrugBruton's Tyrosine Kinase (BTK) inhibitor
Sonrotoclax
DrugB-cell lymphoma 2 (BCL2) protein inhibitor
Obinutuzumab
DrugAnti-CD20 monoclonal antibody
Tacabrutideg
DrugBruton's Tyrosine Kinase (BTK) degrader
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Zanubrutinib, Obinutuzumab, and Sonrotoclax (BOSon)Experimental treatment 3 interventions
Group B: Tacabrutideg (BGB-16673), Obinutuzumab, and Sonrotoclax (DOSon)Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Rate 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 enrolled2
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-upSecondary outcomes
1
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 enrolled2
Rate of uMRD at interim (C10D28 for BOSon and C12D28 for DOSon) and after 24 cycles
The proportion of patients achieving uMRD in both PB and BM by ClonoSEQ (cutoff, \<10-5) at interim (C10D28 for BOSon and C12D28 for DOSon) and after 24 cycles
Time frame
Day 1 to interim (C10D28 for BOSon and C12D28 for DOSon) and to after 24 cycles3
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 enrolled4
Progression-free survival (PFS), Overall Survival (OS), MRD4-Free Survival, and MRD5-free survival
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 enrolledSponsors and contacts
Click on the lead sponsor to view all of their trials.
Massachusetts General Hospital
Lead sponsor
BeOne Medicines
Collaborator
Source ClinicalTrials.gov