Momelotinib in VEXAS Syndrome
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGroupe Francophone des Myelodysplasies
About this trial
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.
Eligibility criteria
Qualifiers
ECOG (Eastern Cooperative Oncology Group) performance status 0-2 at the time of screening
Age ≥ 18 years
Written informed consent
Diagnosis of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory and Somatic) syndrome with UBA1 (Ubiquitin Like Modifier Activating Enzyme 1) mutation and clinically symptomatic disease requiring immunosuppressive treatment and at least 10mg/d of glucocorticoids
Disqualifiers
Patients with MDS (Myelodysplastic syndrome) scheduled for allogeneic stem cell transplant or high risk MDS according to IWG (International Working Group) 2023
Patients who are or have been already treated with Janus Kinase (JAK) inhibitors for VEXAS syndrome or another indication
Patients who are unable to receive a starting daily dose of momelotinib of at least 100 mg
Subjects with any other active malignancies are not eligible, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which subject has been disease-free for at least 3 years
Trial design
Treatments tested in this trial
- Momelotinib treatment
Treatment groups
57 Participants
are divided into 1 treatment groupSponsors and collaborators
Groupe Francophone des Myelodysplasies
Lead sponsor
GlaxoSmithKline
Collaborator
Source ClinicalTrials.gov