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.
...
Moderate or severe cGVHD (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per NIH criteria
cGVHD that did not respond to >=2 lines of prior systemic therapy.
Karnofsky performance score >=60%
Age >=18 years.
Acute GVHD that is active as defined by exhibiting current signs or symptoms of disease without any chronic GVHD (classic and late-acute GVHD per NIH consensus criteria); participants with a clinical presentation consistent with overlapping acute GVHD with concurrent chronic GVHD will be eligible
Treatment with ruxolitinib within 24 hours, or ibrutinib within the <=14 days prior to treatment initiation.
Active HIV-1 (detectable HIV viral load), or Hepatitis B (HBV) and/or Hepatitis C (HCV) infection (positive HBV or HCV viral load in the setting of positive HBV core antibody or surface antibody or HCV antibody).
symptomatic congestive heart failure
Sequential
Pacritinib
DrugPacritinib 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.
Phase I: Safety of pacritinib in refractory cGVHD.
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)
the fraction with clinical responses reported separately by arm, with a separate 95% confidence interval for each cohort.
Phase I: Pharmacokinetics (PK)
The secondary endpoint for PK properties includes measures such as AUC, half-life, and steady-state concentration.
Phase 2: Safety
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
Rate of reduction and/or discontinuation of immunosuppressive therapy; response by organ system; time to response; duration of best response; and, failure-free survival
Click on the lead sponsor to view all of their trials.
