Momelotinib in VEXAS Syndrome
brief summary
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.
detailed description
During safety run-in phase, the three fixed dose levels tested are :
* Dose level (DL) -1: 150 mg once daily (QD) * DL1: 200 mg QD * DL2: 300 mg QD. Between 6 and 18 patients will be enrolled during the safety run-in phase. Up to 39 patients could be included in the phase II study and will be treated with momelotinib at the maximum tolerated dose preliminary fixed during the safety run-in phase.
Baseline steroids daily dose required for VEXAS inflammatory manifestations will be defined during screening period (28 days period) for each patient. It is defined as the minimal daily dose of steroids used in the last 14 days prior momelotinib onset (according to physician disposition) that allow disease control. In case of related VEXAS inflammatory manifestation during screening period with a first fixed dose, an increased dose of steroids should be evaluated during at least an extra 14 days prior momelotinib onset. This baseline dose defined during screening period will be used for response criteria during follow-up.
Momelotinib treatment will be discontinued after 24 weeks at optimal dosing regimen (up to 300 mg/day), in case of absence of response.
Treatment might also be discontinued during follow-up in case of loss of response/hematological progression or non-tolerable adverse event.
official title
A Single-arm Phase II With safety-run-in Multicenter Study of Momelotinib in Patients With VEXAS Syndrome With or Without Associated Myelodysplastic Syndrome