Daratumumab Plus Ibrutinib in Patients With Waldenstrӧm's Macroglobulinemia

Waldenstrom Macroglobulinemia Clinical Trial

Official title: A Phase II Study of Daratumumab Plus Ibrutinib in Patients With Waldenstrӧm's Macroglobulinemia

Status Terminated

Clinical Trial Summary

This study evaluates the safety and efficacy of daratumumab in combination with ibrutinib in patients with Waldenstrӧm's macroglobulinemia (WM). The study will evaluate this combination in two cohorts. Cohort A will comprise of ibrutinib naïve WM patients. Patients in this cohort may be treatment naïve or relapsed but who remain ibrutinib naïve. 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.

Clinical Trial 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 naïve 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 naïve 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. ;

Related Conditions & MeSH terms

• Hypergammaglobulinemia
• Waldenstrom Macroglobulinemia
• Waldenstrom's Disease
• Waldenstrom's Macroglobulinaemia, Without Mention of Remission
• Waldenstrom's Macroglobulinemia of Lymph Nodes
• Waldenstrom's Macroglobulinemia Recurrent
• Waldenstrom's Macroglobulinemia Refractory
• Waldenström; Hypergammaglobulinemia

• NCT number: NCT03679624
• Study type: Interventional
• Source: Weill Medical College of Cornell University
• Status: Terminated
• Phase: Phase 2
• Start date: July 30, 2020
• Completion date: October 13, 2020