Bendamustine, Rituximab and Acalabrutinib in Waldenstrom's Macroglobulinemia (BRAWM)
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|ClinicalTrials.gov Identifier: NCT04624906|
Recruitment Status : Not yet recruiting
First Posted : November 12, 2020
Last Update Posted : November 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Waldenstrom Macroglobulinemia||Drug: Acalabrutinib Drug: Bendamustine Drug: Rituximab||Phase 2|
This is a multi-centre, open label, single-arm, phase II clinical trial in untreated patients with WM. Patients will require a biopsy to confirm the pathology and molecular testing for MYD88, CXCR4 and P53 mutations. A bone marrow aspiration and biopsy will be performed to document WM and MRD. Participants will be classified into clinical risk categories based on the International Prognostic Scoring (IPS) System for WM. Symptomatic, previously untreated patients will receive SOC bendamustine and rituximab for 6 28-day cycles. Bendamustine will be given intravenously at 90 mg/m2 on days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2 intravenously for the first cycle and 1400 mg subcutaneously OR 375 mg/m2 intravenously for subsequent cycles (as per institutional procedures)).
Concomitantly, participants will receive 100 mg of the investigational product, acalabrutinib, orally for 1 year (365 days) at 100 mg BID. Patients will have pre-treatment computed tomography (CT) scans, and CT scans at 7, 12 and 18 months. Best objective response will be documented using the criteria from the Sixth International Workshop on Waldenstrom's Macroglobulinemia. Assessment of metabolic uptake by positron emission tomography (PET) scan is not considered appropriate for WM as WM usually do not take up fluorodeoxyglucose (FDG). Patients with WM will also have disease assessed using measurements of serum IgM, serum protein electrophoresis (SPE), immunofixations (IFA), and viscosity assessments measured serially. A bone marrow aspiration and biopsy will be done before treatment and at response assessment at cycle 6 and will be repeated if positive. Durability of response will also be assessed at 18 months.
Participants will be followed by extended follow-up by telephone for up to 6 years to obtain data on the secondary endpoints.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||59 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Bendamustine, Rituximab and Acalabrutinib|
|Masking:||None (Open Label)|
|Official Title:||A Multi-Center, Open-Label, Single-Arm Phase II Trial of Bendamustine, Rituximab and the Second Generation BTK Inhibitor Acalabrutinib in Previously Untreated Waldenstrom's Macroglobulinemia|
|Estimated Study Start Date :||December 2020|
|Estimated Primary Completion Date :||December 2024|
|Estimated Study Completion Date :||March 2030|
Experimental: Single arm intervention
100 mg acalabrutinib (ACP-196) oral capsules twice daily for 1 year
Bendamustine and rituximab will be given for 6 x 28-day cycles. Bendamustine will be given intravenously at 90 mg/m2 on days 1 and 2 of each cycle. Rituximab will be given on day 1 of each cycle (375 mg/m2 intravenously for the first cycle and 1400 mg subcutaneously OR 375 mg/m2 intravenously for subsequent cycles (as per institutional procedures).
100 mg oral capsules twice daily for 1 year
Other Name: Calquence
90 mg/m2 on days 1 and 2 of each cycle.
Other Name: Treanda
day 1 of each cycle (375 mg/m2 intravenously for the first cycle and 1400 mg subcutaneously OR 375 mg/m2 intravenously for subsequent cycles (as per institutional procedures).
Other Name: Rituxan
- Best combined complete response (CR) and very good partial response (VGPR) [ Time Frame: through study completion, an average of 1 year - cycle 7, 12 (day 1 of 28 day cycle) ]To document the best combined CR and VGPR rate of first line treatment with bendamustine & rituximab plus acalabrutinib in patients with Waldenstrom's macroglobulinemia using the criteria from the Sixth International Workshop on Waldenstrom's Macroglobulinemia. Best response will be recorded within the first twelve months of treatment. These include assessments at the beginning treatment cycles; 2,3,4,5,6 , 7,10, and 12. For each participant, the best response will be selected at any of these timepoints to be used as the best objective response for that participant. The results from each participant will be pooled and participants whose best response at any of these time points is either CR or VGPR will be added together to derive the overall best CR/VGPR rate for the study population.
- Overall objective response and partial response [ Time Frame: 6 and 12 months ]using criteria from 6th international workshop on WM
- Documentation of minimal residual disease (MRD) rate [ Time Frame: through study completion, an average of 18 months cycle 7, 12 and 18 (each cycle is 28 days) ]MRD will be assessed at three on treatment timepoints (before start of cycles 7, 12, 18). MRD will be measured from two body compartments-peripheral blood and bone marrow. MRD will be recorded and will be reported based on the limit of detection of the assay (to be determined). Results will be pooled and rates of MRD negativity for the assay will be recorded at each time point for the pooled patients and for each of the two body compartments that are being assessed.
- Documentation of overall survival [ Time Frame: Up to 6 years post first dose ]OS will be determined using the time from first day of study treatment to death for each patients. Results for each patient will be pooled to derive an overall survival rate.
- Documentation of progression free survival [ Time Frame: Up to 6 years post first dose ]PFS will be defined as the time from first dose of study treatment to the first objective documentation of progressive disease (PD), the start of an alternative anticancer therapy, or death from any cause during study. Results for each patient will be pooled to derive an overall progressive free survival rate. Participants not meeting criteria for PD will be followed by telephone every 6 months for up to six years from the time of first dose.
- Toxicities graded according to the NCI Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE, v5.0)] [ Time Frame: Up to 30 days following last dose ]A descriptive analysis of safety will be performed with descriptions of frequency and grade of the adverse events including adverse events of special interest such as hypertension, cardiac arrhythmias and bleeding events. The common toxicities described in the NCK common terminology criteriae for adverse events (NC CTAE v5.0) will be documented and grade in each patient at each visit throughout the trial. Rates and severity of all of these toxicity will be collected and reported.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04624906
|Contact: Neil L Berinstein, MD||416-480-6100||BRAWM@sunnybrook.ca|
|Principal Investigator:||Neil L Berinstein, MD||Sunnybrook Research Institute|