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A Single-arm Phase II With safety-run-in Multicenter Study of Momelotinib in Patients With VEXAS Syndrome With or Without Associated Myelodysplastic Syndrome
Multicenter, phase II trial with safety run-in to evaluate the efficacy and safety of momelotinib in patients with VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome with or without associated myelodysplastic syndrome (MDS). The study will consist of two consecutive steps, a dose-finding safety run-in and a single-arm prospective phase II. During safety run-in phase, three fixed dose levels will be tested according to a 3+3 design, using cohorts of size 3 in order to establish the maximum tolerated dose. After this safety run-in phase, patients included in phase II will be treated with momelotinib at the maximum tolerated dose preliminary fixed. Patients included in the phase II will receive momelotinib continuously until disease progression or loss of response, at physician's discretion. All patients included in the study will receive glucocorticoids (prednisone/prednisolone equivalent) at baseline (at least \> 10mg/day). Response assessment regarding VEXAS related symptoms will be evaluated after 4, 12, 24 and 48 weeks. Response assessment regarding MDS features will be evaluated at 12 and 24 weeks.
Details
| Lead sponsor | Groupe Francophone des Myelodysplasies |
|---|---|
| Phase | Phase 2 |
| Status | RECRUITING |
| Enrolment | 57 |
| Start date | 2025-11-25 |
| Completion | 2028-11 |
Conditions
- VEXAS Syndome
- Myelo Dysplastic Syndrome
Interventions
- Momelotinib treatment
Primary outcomes
- Determination of the maximum tolerated dose of momelotinib — First 4-week cycle of momelotinib treatment
The maximum tolerated dose (MTD) is defined by a target dose-limiting toxicities (DLT) rate of 30%, assessed during the observation window by a 3+3 design. The 3+3 design will enroll a first cohort of 3 patients at the starting dose of 200 mg/d: * If 0 of the 3 patients at the dose of 200 mg/d experienced a DLT during the first 4-week cycle of momelotinib, the dose will escalate to 300 mg/d for the next cohort. * If 1 of the 3 patients at the dose of 200 mg/d has a DLT, a cohort of three additional patients will be treated at the same dose of 200 mg/d. * If \> 1 patient of the 3 patients at the dose of 200 mg/d have a DLT, the dose will de-escalate to 150 mg/d for the next cohort. The same process will be repeated until reaching the MTD. In total, between 6 and 18 patients will be enrolled during this safety run-in phase. - Clinical efficacy — During the 24 first weeks of momelotinib treatment
Determination of overall clinical response rate at 24 weeks after momelotinib initiation on VEXAS related symptoms (including complete (CR) or partial response (PR)) : * CR includes complete disappearance of symptoms related to systemic inflammation according to treating physician and daily dose of steroids ≤ 10 mg/d (equivalent prednisolone). * PR includes complete disappearance of symptoms related to systemic inflammation according to treating physician and reduction of at least 50% of daily dose steroids compared to baseline and/or daily dose of steroids \> 10 mg/d.
Countries
France