Momelotinib in VEXAS Syndrome

Prior treatment

• Patients who are or have been already treated with Janus Kinase (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 momelotinib
• Previous history of Progressive Multifocal Leuko-encephalopathy

Other illness

• Patients with MDS (Myelodysplastic syndrome) scheduled for allogeneic stem cell transplant or high risk MDS according to IWG (International Working Group) 2023
• 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 Human Immunodeficiency Virus, Hepatitis B Virus, Hepatitis C Virus
• 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
• Active gastrointestinal conditions that may affect absorption
• Known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients

Other

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

• 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
• Patients 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/immunomodulatory therapy than glucocorticoids, a wash out period of 28 days is required prior momelotinib onset
• Erythropoietin/luspatercept used as a growth factor treatment is not allowed 28 days prior enrollment
• Adequate liver function (serum transaminases ≤ 3 x ULN (Upper Limits of Normal), Bilirubin ≤ 1.5 x ULN (isolated bilirubin \> 1.5 x ULN is acceptable if bilirubin fractionated and direct bilirubin \< 35%)
• Adequate renal function (creatinine clearance with MDRD (Modification of Diet in Renal Disease) formula \> 30 ml/min)
• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must:
  • Have a negative serum or urine pregnancy test within 24 hours prior to beginning treatment on this study. Lactating patients are excluded.
  • 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.
  • Agree to learn about the procedures for preservation of egg before starting treatment.
• Male patients must:
  • 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.
  • Agree to learn about the procedures for preservation of sperm before starting treatment.