Momelotinib treatment for VEXAS syndrome

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter phase II study with a safety run-in using a 3+3 dose‑finding design to establish a maximum tolerated dose of momelotinib (tested at 150 mg, 200 mg, and 300 mg once daily). Between 6 and 18 patients will enter the safety run-in, and up to 39 patients will be treated in the single-arm phase II at the preliminarily fixed dose. All participants will start on a defined baseline steroid dose (≥10 mg/day prednisone equivalent) and continue momelotinib until disease progression, loss of response, intolerable toxicity, or lack of response after 24 weeks at the optimal dose. The trial enrolls adults with confirmed UBA1-mutant VEXAS who have symptomatic disease requiring immunosuppression and an ECOG performance status of 0–2.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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:

  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.

Exclusion Criteria:

* 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
* 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
* 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
* Previous history of Progressive Multifocal Leuko-encephalopathy
* Active gastrointestinal conditions that may affect absorption
* No affiliation to a health insurance system
* Known hypersensitivity to the study investigational medicinal product, the metabolites, or formulation excipients

Where it's running

• CHU d'Angers - Service des Maladies du sang
  Angers, France Recruiting
• CH Lyon sud - Service d'Hématologie Clinique
  Pierre-Bénite, France Recruiting
• CHU Estaing - Service d'Hématologie Clinique
  Clermont-Ferrand, France Not yet recruiting
• Hôpital Claude Huriez - Service de Médecine Interne
  Lille, France Not yet recruiting
• CHU Nantes - Hôtel Dieu - Service d'Hématologie Clinique
  Nantes, France Not yet recruiting
• Hôpital Saint Louis - Service hématologie séniors
  Paris, France Not yet recruiting

Study contacts

• Principal investigator: Maël HEIBLIG, MD — CH Lyon Sud
• Study coordinator: Maël HEIBLIG, MD
• Email: mael.heiblig@chu-lyon.fr
• Phone: +33 4 72 11 74 01

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.