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)

NCT05531786 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10000643000643-C
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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. ...

Conditions

Graft vs Host Disease

Keywords

Anti-Inflammatory; Fibrosis; Inflammation; Refractory; Systemic Therapy

Outcome Measures

Primary Outcomes (2)

• 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.

  60 days

• Phase II: Overall response rate (ORR)

  the fraction with clinical responses reported separately by arm, with a separate 95% confidence interval for each cohort.

  6 months

Secondary Outcomes (3)

• Phase I: Pharmacokinetics (PK)

  every 3 months through up to 12 months of treatment

• Phase 2: Safety

  every 3 months through up to 12 months of treatment

• Phase 2: Clinical outcomes

  every 3 months through up to 12 months of treatment

Study Arms (3)

Arm 2 - Low-dose

EXPERIMENTAL

Expansion dosing to evaluate the efficacy of pacritinib 100 mg PO BID

Drug: Pacritinib

Arm 3 - High-dose

EXPERIMENTAL

Expansion dosing to evaluate the efficacy of pacritinib 200 mg PO BID

Drug: Pacritinib

Escalating doses of treatment

EXPERIMENTAL

Escalating doses of pacritinib to confirm safety in cGVHD

Drug: Pacritinib

Interventions

Pacritinib DRUG

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.

Arm 2 - Low-dose; Arm 3 - High-dose; Escalating doses of treatment

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Disease that has failed prior systemic therapy will be defined as follows:
• a) For prior corticosteroid-containing regimens, disease that:
• i) recurs after achievement of a CR, or
• ii) progresses after achievement of a PR, or
• iii) progresses after at least 1 week of prednisone equivalent of 1 mg/kg/day, or
• iv) is stable and persistent after at least 4 weeks of a prednisone equivalent of 0.5 mg/kg/day
• OR,
• b) For other systemic therapies, disease that:
• i) recurs after achievement of CR, or
• ii) progresses after achievement of a PR, or
• iii) is stable and persistent despite 4 weeks of therapeutic dosing of systemic therapy
• Karnofsky performance score \>=60%
• Age \>=18 years.

You may not qualify if:

• 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, or ibrutinib within the for \<= 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).
• Participants with the following cardiac conditions at screening:
• symptomatic congestive heart failure
• unstable angina pectoris
• uncontrolled cardiac dysrhythmias
• QTc(F) prolongation \>450 ms or other factors that increase the risk for QT prolongation (i.e., heart failure, or a history of long QT interval syndrome).
• Left ventricular ejection fraction \<= 50% by transthoracic echocardiogram (TTE) at screening.
• Participants with poor pulmonary function as defined by a forced expiratory volume in the first second (FEV1) \<= 39% calculated using the USA-ITS-NIH equation.
• Participants with evidence of ongoing hemorrhage, active signs/symptoms of bleeding, or history of severe bleeding complications in the one year prior to enrollment.
• Concurrent treatment with any other investigational agents.
• Concurrent use of strong CYP3A4 inducers or inhibitors, must stop 2 weeks prior study drug initiation.
• Known hypersensitivity to JAK inhibitors.
• Participants who are unwilling to accept blood transfusions.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

University of Miami

Miami, Florida, 33101, United States

RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Graft vs Host Disease; Fibrosis; Inflammation

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Najla El Jurdi, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rania S Hishmeh, R.N.

CONTACT

(240) 858-3681; rania.hishmeh@nih.gov

Najla El Jurdi, M.D.

CONTACT

(240) 992-4033; najla.eljurdi@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2022
• First Posted: September 8, 2022
• Study Start: March 6, 2023
• Primary Completion (Estimated): July 22, 2027
• Study Completion (Estimated): July 22, 2027
• Last Updated: March 27, 2026

Record last verified: 2025-11-21

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (2)