Last updated on August 2020

Daratumumab Plus Ibrutinib in Patients With Waldenstr m's Macroglobulinemia

Brief description of study

This study evaluates the safety and efficacy of daratumumab in combination with ibrutinib in patients with Waldenstrm's macroglobulinemia (WM). The study will evaluate this combination in two cohorts. Cohort A will comprise of ibrutinib nave WM patients. Patients in this cohort may be treatment nave or relapsed but who remain ibrutinib nave. Cohort B will comprise of patients who are currently receiving ibrutinib but whose response to treatment has plateaued. In this cohort, daratumumab will be added on to ibrutinib in an attempt to deepen response.

Detailed Study Description

This is a multi-center, two cohort Phase 2 clinical trial investigating the effectiveness of adding daratumumab to ibrutinib in WM patients. Cohort A will consist of patients who are ibrutinib nave and appropriate for ibrutinib based treatment. Cohort B will consist of patients who have achieved a response plateau less than a complete remission (CR) on single agent ibrutinib. Subjects in Cohort A will be identified by their treating physician and eligible for enrollment if they are treatment nave or relapsed after 1 prior therapy for WM and eligible for ibrutinib based treatment.

Subjects in Cohort B will be identified by their treating physician and eligible for enrollment if they have had at least 6 months of exposure to single agent ibrutinib and demonstrate an IgM response plateau defined by two IgM measurements, at least 8 weeks apart that have changed <15% from the previous mark. In Cohort B response assessment will be measured from initial IgM level prior to ibrutinib initiation.

Enrolled subjects will be prescribed commercial ibrutinib, 420mg PO daily. The investigational agent, daratumumab will be administered based on FDA approved dosing in multiple myeloma (16mg/kg) with 8 weekly induction treatments during Cycles 1 and 2, followed by every other week dosing for Cycles 3-6, then monthly dosing from Cycle 7 until Cycle 25 at which point subjects will continue with ibrutinib as monotherapy until Cycle 52 (4 years total) which is the predefined study completion for enrolled subjects at which point they will complete follow-up. Study visits and response assessments with IgM measurements will occur with each cycle for the first year then every three cycles after cycle 13. Subjects with measureable extramedullary disease will have CT scans every 6 cycles until radiographic CR. Patients will be considered evaluable for response if they completed the initial 8 weeks of daratumumab induction therapy and evaluable for toxicity if receiving one dose of daratumumab. Patients will continue on combination therapy for 2 years or until disease progression or unacceptable toxicities at which point subjects will come off trial. Patients achieving a CR after two years of combination therapy will be given an option to continue with single agent commercial ibrutinib.

Clinical Study Identifier: NCT03679624

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Weill Cornell Medicine

New York, NY United States
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Recruitment Status: Open

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