Testing pacritinib for treating severe chronic graft-versus-host disease after stem cell transplant

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)

This study is testing if a new oral medication called pacritinib can help adults with severe chronic graft-versus-host disease who haven't found relief from other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 120 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: ruxolitinib, ibrutinib, prednisone, pacritinib
• Locations: 2 sites (Miami, Florida and 1 other locations)
• Trial ID: NCT05531786 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and efficacy of pacritinib, a JAK2/IRAK1/CSF1R inhibitor, in patients with moderate to severe chronic graft-versus-host disease (cGVHD) who have not responded to at least two prior treatments. Participants aged 18 and older will undergo screening, including blood and urine tests, and may receive additional imaging or specialized tests. The drug will be administered orally at home, with participants maintaining a medication diary to track their dosage and schedule. The study is designed in two phases: the first to assess safety and the second to evaluate efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with moderate or severe cGVHD that has not responded to two or more lines of systemic therapy.

Not a fit: Patients with mild cGVHD or those who have not undergone prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from refractory chronic graft-versus-host disease.

How similar studies have performed: Other studies have shown promising results with JAK inhibitors in treating similar conditions, suggesting potential for success with this approach.

Eligibility criteria

-INCLUSION CRITERIA:

1. Moderate or severe cGVHD (after allogeneic hematopoietic stem cell transplantation) diagnosed and staged per NIH criteria
2. 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
3. Karnofsky performance score \>=60%
4. Age \>=18 years.
5. If participant is taking systemic therapy for cGVHD at the time of enrollment, they must be on a stable or tapering dose in the preceding 4 weeks.
6. Participants must have adequate organ and marrow function as defined below:

   * absolute neutrophil count \>=1,000/mcL
   * platelets \>=50,000/mcL
   * total bilirubin \<=1.5 X institutional upper limit of normal

   OR

   \<=3 X institutional upper limit of normal in participants with Gilbert's syndrome
   * AST(SGOT)/ALT(SGPT) \<=3 X institutional upper limit of normal
   * creatinine clearance \>=50 mL/min/1.73 m\^2 per Cockroft-Gault
7. Primary malignancy for which the participant received transplant has been in complete clinical remission and stable for 3 months prior to enrollment on study.
8. Individuals of child-bearing potential (IOCBP) and individuals able to father a child with a partner able to become pregnant who are sexually active must agree to use one (1) highly effective (e.g., intrauterine device \[IUD\], surgical) or two (2) effective forms of contraception (e.g., barrier method) at study entry, for the duration of study treatment, and for at least 90 days after last study drug exposure.
9. Ability of participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. 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
2. Treatment with ruxolitinib, or ibrutinib within the for \<= 14 days prior to treatment initiation.
3. 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).
4. 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).
5. Left ventricular ejection fraction \<= 50% by transthoracic echocardiogram (TTE) at screening.
6. 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.
7. Participants with evidence of ongoing hemorrhage, active signs/symptoms of bleeding, or history of severe bleeding complications in the one year prior to enrollment.
8. Concurrent treatment with any other investigational agents.
9. Concurrent use of strong CYP3A4 inducers or inhibitors, must stop 2 weeks prior study drug initiation.
10. Known hypersensitivity to JAK inhibitors.
11. Participants who are unwilling to accept blood transfusions.
12. Pregnancy or breastfeeding.
13. Participants with any active, uncontrolled viral, bacterial, or fungal infection are excluded.
14. Other malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix or breast which requires active treatment.
15. Uncontrolled intercurrent illness evaluated by history, physical exam and chemistries or situation that would limit compliance with study requirements.

Where this trial is running

Miami, Florida and 1 other locations

• University of Miami — Miami, Florida, United States (Recruiting)
• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Najla El Jurdi, M.D. — National Cancer Institute (NCI)
• Study coordinator: Rania S Hishmeh, R.N.

Conditions Graft vs Host Disease; Anti-Inflammatory; Fibrosis; Inflammation; Refractory; Systemic Therapy