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)
- Registration Number
- NCT05531786
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
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- 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 greater than or equal to18 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.
* Total maximum number of participants to be enrolled is 30, with accrual ceiling set at 50 participants.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 2 - Low-dose Pacritinib Expansion dosing to evaluate the efficacy of pacritinib 100 mg PO BID Arm 3 - High-dose Pacritinib Expansion dosing to evaluate the efficacy of pacritinib 200 mg PO BID Escalating doses of treatment Pacritinib Escalating doses of pacritinib to confirm safety in cGVHD
- Primary Outcome Measures
Name Time Method Phase I: Safety of pacritinib in refractory cGVHD. 60 days grades and types of toxicity reported at each dose level. The overall estimate of the fraction of patients who have a DLT at the MTD will be reported.
Phase II: Overall response rate (ORR) 6 months the fraction with clinical responses reported separately by arm, with a separate 95% confidence interval for each cohort.
- Secondary Outcome Measures
Name Time Method Phase 2: Safety every 3 months through up to 12 months of treatment Toxicities identified from day 1 of study drug, collected every 2 weeks through cycle 4, then per cycle through 30 days after the study drug administration. AEs are reported by type and grade
Phase 2: Clinical outcomes every 3 months through up to 12 months of treatment Rate of reduction and/or discontinuation of immunosuppressive therapy; response by organ system; time to response; duration of best response; and, failure-free survival
Phase I: Pharmacokinetics (PK) every 3 months through up to 12 months of treatment The secondary endpoint for PK properties includes measures such as AUC, half-life, and steady-state concentration.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States