Momelotinib in VEXAS syndrome

Prior treatment

• Patients with MDS currently scheduled for allogeneic stem cell transplant or high risk MDS according to IWG 2023.
• Patients who are or have been already treated with JAK inhibitors for VEXAS syndrome or another indication.
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 12 weeks prior to initiation of MMB.
• Previous history of Progressive Multifocal Leuko-encephalopathy (PML)

Other illness

• Active gastrointestinal conditions that may affect absorption
• Known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients.
• 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.
• Known infection with acute and chronic active HIV, HBV, HCV infections.
• Any medical or psychiatric condition not allowing the informed consent of the subject
• Presence of clinically meaningful active bacterial, fungal, parasitic or viral infection which requires therapy

Other

• No affiliation to a health insurance system.
• Patients who are unable to receive a starting daily dose of MMB of at least 100 mg.

• ECOG performance status 0-2 at the time of screening
• Adequate liver function (serum transaminases ≤ 3N, Bilirubin ≤ 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%))
• Adequate renal function (creatinine clearance with MDRD formula > 30 ml/min)
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must: 1- Have a negative serum or urine pregnancy test within 24-hours prior to beginning treatment on this study. Lactating patients are excluded. 2- Agree to use, and to be able to comply with, effective contraception without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy (including doses interruptions) and for 12 weeks after the end of the study drug therapy. 3- Agree to learn about the procedures for preservation of egg before starting treatment.
• Male patients must: 1- Agree the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment, even if disruption of treatment and during 12 weeks after end of treatment. 2- Agree to learn about the procedures for preservation of sperm before starting treatment.
• Age ≥ 18 years
• Written informed consent
• Diagnosis of VEXAS syndrome with UBA1 mutation and clinically symptomatic disease requiring corticosteroid therapy with more than 10 mg/day of prednisone equivalent
• With uncontrolled symptoms related to VEXAS with prior treatment line(s) (including steroids)
• Patients refractory/dependent to steroids
• Single concomitant steroids therapy (e.g. prednisone or equivalent) at the time of inclusion is allowed
• For patients treated with other immunosuppressive/immuno-modulatory therapy than glucocorticoids, a wash out period of 28 days is required prior MMB onset
• Erythropoietin/luspatercept used as a growth factor is not allowed 28 days prior enrollment