Pacritinib in Vacuoles, E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome

Conditions

• E1 Ubiqutin-activating Enzyme, X-linked, Autoinflammatory, Somatic Syndrome
• VEXAS
• Vexas Syndrome

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pacritinib — DRUG
  Starting dose is 200 mg twice per day by mouth. Dose level -1 is 100 mg twice per day by mouth.

Study Details

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.

Key Dates

Start date

Feb 13, 2025

Status verified

Jul 2025

Primary completion

Mar 31, 2027

Completion

Feb 28, 2029

Study Design

Enrollment

15 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Dose De-Escalation (Safety Run-in): Pacritinib
  Assigned dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment.
• Experimental: Dose Expansion: Pacritinib
  Recommended phase II dose of pacritinib by mouth twice per day. Each cycle is 28 days and participants can receive up to 12 cycles of treatment.

Primary Outcome Measure

Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: Through completion of cycle 1 (estimated to be 28 days) ]

Central Contacts

• Meagan A Jacoby, M.D., Ph.D.
  314-454-8306
  [email protected]

Locations (1)

Find similar trials in St Louis, MO

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