Actively Recruiting
Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
Led by Washington University School of Medicine · Updated on 2025-07-16
15
Participants Needed
1
Research Sites
210 weeks
Total Duration
On this page
Sponsors
W
Washington University School of Medicine
Lead Sponsor
S
Swedish Orphan Biovitrum
Collaborating Sponsor
AI-Summary
What this Trial Is About
VEXAS (vacuoles, E1 ubiqutin-activating enzyme, X-linked, autoinflammatory, somatic syndrome) is a recently described disorder with severe hematologic and rheumatologic manifestations caused by somatic variants in the ubiquitin- activating enzyme gene, UBA1, that is acquired in hematopoietic progenitor cells. Patients are often debilitated by autoinflammatory symptoms and there is currently no standard of care available. There is a clinically unmet need for better therapies in VEXAS Syndrome. There have been no prospective clinical trials of JAK-I in VEXAS syndrome. The investigators hypothesize that pacritinib, as a JAK2/IRAK1 inhibitor with a manageable safety profile in myelofibrosis patients with thrombocytopenia, will improve the autoinflammatory and hematologic manifestations of VEXAS syndrome with a tolerable toxicity profile. The investigators propose a single arm, pilot Phase 1 study evaluating the safety and tolerability of pacritinib in patients with VEXAS syndrome with an initial safety run-in phase of 6 patients treated with pacritinib 200mg twice daily (BID) on days 1-28 of a continuous 28 day cycle. If no more than 1 patient experiences a dose-limiting toxicity (DLT), the investigators will enroll an expansion cohort to gain additional toxicity and efficacy data, for a total enrollment of 15 patients. If more than 1 patient experiences a DLT during the safety run-in phase, the investigators will decrease the dose to 100 mg BID, and if no more than 1 of 6 patients experiences a DLT, the investigators will complete the expansion cohort as above for up to a total enrollment of 15 patients. If more than 1 patient experiences a DLT at 100 mg BID, the investigators will discontinue the study. Patients will be treated for up to 12 cycles.
CONDITIONS
Official Title
Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must have a UBA1 mutation with variant allele frequency of at least 2% and at least one clinical sign of VEXAS syndrome such as skin rash, vasculitis, chondritis, eye inflammation, genitourinary inflammation, arthritis, lung inflammation, fever, thrombosis, enlarged spleen or liver, heart inflammation, or low blood counts.
- Patients with VEXAS syndrome who have never taken a JAK inhibitor are eligible.
- Patients previously treated with JAK inhibitors other than pacritinib may enroll after a 28-day washout if symptoms are uncontrolled or corticosteroids cannot be reduced below 10 mg prednisone daily.
- Stable corticosteroid dose must be maintained for at least 14 days before starting pacritinib.
- Age 18 years or older.
- ECOG performance status of 3 or less.
- Adequate organ function including neutrophil count ≥ 0.5 K/cumm, platelets ≥ 25 K/cumm, PT/PTT less than 2.5 times normal, total bilirubin ≤ 1.5 times normal, liver enzymes ≤ 3 times normal, and creatinine clearance ≥ 30 mL/min.
- QTcF interval less than 480 milliseconds.
- Agreement to use highly effective contraception during and 30 days after study if applicable.
- Ability to understand and sign informed consent.
- Patients with myelodysplastic syndromes or plasma cell disorders not on active treatment may participate with supportive care allowed.
You will not qualify if you...
- Prior use of pacritinib.
- Use of other JAK inhibitors within 28 days before starting pacritinib.
- Currently receiving other investigational drugs unless 28-day washout completed.
- Thrombotic events within 60 days before enrollment.
- Recent significant bleeding within 7 days before enrollment.
- Active or acute infections.
- History of malignancy within 2 years except for certain blood disorders or treated non-melanoma skin cancers.
- Significant cardiovascular disease or abnormal heart rhythms.
- Current use of immunosuppressants (other than corticosteroids), DMARDs, or biologic cytokine inhibitors unless 28-day washout completed.
- Allergic reactions to similar compounds as pacritinib.
- Concurrent use of strong CYP3A4 inhibitors or inducers unless 28-day washout completed.
- Moderate or severe liver impairment.
- Pregnant or breastfeeding; women of childbearing potential must have negative pregnancy tests before starting.
- Known active HIV, hepatitis B or C infections.
- Latent tuberculosis; must have negative T-Spot test at screening.
AI-Screening
AI-Powered Screening
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Trial Site Locations
Total: 1 location
1
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Actively Recruiting
Research Team
M
Meagan A Jacoby, M.D., Ph.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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