NCT05531786

Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in Refractory Chronic Graft-Versus-Host Disease (cGVHD) After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

Background: Chronic graft-versus-host disease (cGVHD) is an immune system disorder that can occur in people who have had a stem cell transplant. cGVHD can affect multiple organs and increase risk of disability and death. New treatments are needed to treat cGVHD after stem cell transplant. Objective: To test a drug (pacritinib) in people with moderate or severe cGVHD that has not responded to previous treatment. Eligibility: People aged 18 years and older with moderate or severe cGVHD that has not responded to 2 or more lines of previous treatment. Design: Participants will be screened. They will have blood and urine tests. They will have tests of their heart and lung function. They may also have a CT scan. Some may have other specialized tests. Participants will take the study drug at home every day. Pacritinib is a capsule taken by mouth. The study doctor will determine the dosage and schedule. Participants will keep a medication diary. They will record the date and time of each drug dose and any missed doses. Participants will visit the clinic every 2 weeks for the first 4 months. Then they will visit the clinic once every 4 weeks. They will have blood and urine tests. During some visits, other screening tests will be repeated, and participants will fill out questionnaires about their quality of life. Photographs may be taken of skin rashes and joints affected by cGVHD. Participants will give saliva samples. Optional biopsies may be taken of the skin and mouth. Participants will take pacritinib for 6 to 12 months if no side effects develop. Follow-up visits will continue for up to 2 years. ...

Detailed description

Background: * Chronic GVHD (cGVHD) is a multi-organ disorder characterized by immune dysregulation, impaired organ function, and decreased survival for hematopoietic stem cell transplantation (HSCT) patients. * The JAK-STAT pathway plays an important role in immune cell development and function, including antigen presenting cells, B- and T-cells, and its activation leads to a cascade promoting a proinflammatory cytokine milieu. * Pacritinib is a JAK2/IRAK1/CSF1R/FLT3 inhibitor, with an established safety and efficacy profile in the treatment of myeloproliferative neoplasms (myelofibrosis) and of acute GVHD. * Pacritinib s immunomodulatory effects suggest therapeutic benefit for cGVHD, without abrogating the graft-versus-leukemia effect after HSCT. Objectives: * Phase I: to determine the safety of pacritinib in participants with refractory cGVHD * Phase II: to determine the efficacy of pacritinib in participants with refractory cGVHD Eligibility: * Moderate or severe cGVHD (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per NIH criteria. * cGVHD that did not respond to at least two prior lines of systemic therapy. * Age \>=18 years. * If participant is taking systemic therapy for cGVHD at the time of enrollment, they must be on stable or tapering doses in the preceding 4 weeks. * Participants must have adequate organ and marrow function. Design: * This Phase I/II study will use a modified 3+3 dose-escalation design, with two planned dose levels of pacritinib, followed by a small efficacy evaluation in a randomized phase II design. * Pacritinib will be given taken orally once or twice daily (based on dose level) on days 1- 28 of a 28-day cycle. * Pacritinib treatment will continue for up to 12 months. cGVHD response will be evaluated at 6 weeks, and 3, 6, 9 and 12 months from the start of pacritinib. All participants will be followed through 2 years post-initiation of pacritinib. * The accrual ceiling set at 50 participants.

Conditions

• Graft vs Host Disease

Interventions

Type	Name	Description
DRUG	Pacritinib	Pacritinib will be given as 100 mg or 200 mg tablets to be taken orally twice daily (12 hours apart) on days 1-28 of a 28 day cycle. Morning and evening should be taken at approximately the same time of day.

Timeline

• Start date: 2023-03-06
• Primary completion: 2027-07-22
• Completion: 2027-07-22
• First posted: 2022-09-08
• Last updated: 2026-03-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study