Zanubrutinib, Bendamustine, Rituximab Prev. Untreated WM
NCT Number: NCT06561347
Acronym: ZEBRA
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Waldenstrom Macroglobulinemia
Interventions: DRUG: Zanubrutinib|DRUG: Bendamustine|DRUG: Rituximab
Sponsor: Massachusetts General Hospital
Collaborators: BeiGene
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 55
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2025-01
Completion Date: 2027-12-01
Locations: Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02215, United States|Dana Farber Cancer Institute, Boston, Massachusetts, 02215, United States

Summary:
The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM).

The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.

Primary Outcome Measures: Very Good Partial Response (VGPR) or Better Response Rate, Assessed using 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria. All participants will be gauged for very good partial response (VGPR) rate or better., Day 1 to 5 years post treatment
Secondary Outcome Measures: Treatment Related Adverse Events, Assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All participants will be followed and assessed for safety and tolerability of the protocol therapy., Day 1 to 5 years post treatment|Overall Response Rate, Assessed per 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria. All participants by mutational status will be monitored for minor response (MR), partial response (PR), very good partial response (VGPR), and complete response (CR)., Day 1 to 5 years post treatment|Major Response Rate, Assessed per 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria. All participants by mutational status will be monitored for partial response (PR), very good partial response (VGPR), and complete response (CR)., Day 1 to 5 years post treatment|Complete Response Rate, Assessed per 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria. All participants by mutational status will be monitored for having resolution of Waldenstrom's Macroglobulinemia (WM) related symptoms, normalization of serum Immunoglobulin M (IgM) levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly. A complete response requires reconfirmation demonstrating normal serum IgM levels, and absence of IgM paraprotein by immunofixation by a measurement repeated at least 2 weeks later., Day 1 to 5 years post treatment|Median Time to Response, All participants by mutational status will be assessed per 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria., Day 1 to 5 years post treatment|Median Time to Major Response, All participants by mutational status will be assessed per 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM11) criteria., From Day 1 until date of major response is first documented, assessed up to 5 years post treatment|Median time to Next Treatment, The duration of time from the initiation of study treatment to the date of commencement of the next line of therapy., From Day 1 until date of next line of therapy is first documented, assessed up to 5 years post treatment|Progression-Free Survival, The duration of time from start of treatment to time of objective disease progression or death. Median, 2-year and 4-year landmark progression free survival (PFS) analysis will be determined., From Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years post treatment|Overall Survival, The duration of time from start of treatment to time of death or last follow-up. Median, 2-year and 4-year landmark overall survival (OS) analysis will be determined., From Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 5 years post treatment