ClinicalTrials.gg
RecruitingNCT05531786Updated Nov 6, 2026

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)

A Phase 1/2 interventional study of Pacritinib in Graft vs Host Disease, sponsored by National Cancer Institute (NCI). Recruiting at 2 sites in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2026-11-06.

Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Started Mar 2023; still recruiting 3 years 8 months later.
Phase
Phase 1/2
Study type
Interventional
Enrollment
50
Allocation
Non-randomized
Ages
18 Years to 120 Years
Sex
All
01

Study 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.

...

Read the 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 24 months. cGVHD response will be evaluated at 6 weeks, and 3, 6, 9 and 12 months from the start of pacritinib. If patient continues treatment beyond 12 months, cGVHD will be evaluated at 15, 18, 21 and 24 months (off treatment timepoint) from the start of pacritinib. All participants will be followed through 3 years post-initiation of pacritinib.
  • The accrual ceiling is set at 50 participants.
02

Conditions studied

  • Graft vs Host Disease

Keywords

  • Anti-Inflammatory
  • Fibrosis
  • Inflammation
  • Refractory
  • Systemic Therapy
03

In context

Graft vs Host Disease

804 studies on the registry are indexed under Graft vs Host Disease; 149 are open to participants now.

This study's planned enrollment of 50 is above the median of 35 across 639 interventional studies indexed under Graft vs Host Disease.

Browse Graft vs Host Disease studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. Moderate or severe cGVHD (after 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 -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. 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:

    • >=1,000/mcL
    • >=50,000/mcL
    • total \<=1.5 X institutional

    OR

    \<=3 X institutional upper limit of normal in participants with Gilbert's syndrome

    • (SGOT)/ALT(SGPT) \<=3 X institutional upper limit of normal
    • >= 35 mL/min per CKD-EPI 2021
  7. Primary 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 (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 system containing levonorgestrel intrauterine devices, surgical) or two (2) effective forms of (e.g., barrier method) at study entry, for the duration of study treatment, and for at least 30 days after last study drug exposure.
  9. Ability of participant to understand and the willingness to sign a written document.

Exclusion criteria

EXCLUSION CRITERIA:

  1. Acute 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 within 24 hours, or ibrutinib within the \<=14 days prior to treatment initiation.
  3. Active -1 (detectable HIV viral load), or (HBV) and/or (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
    • (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. \<= 50% by transthoracic echocardiogram (TTE) at screening.
  6. Participants with poor pulmonary function as defined by a (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 agents.
  9. Concurrent use of strong inducers or inhibitors, must stop 2 weeks prior study drug initiation.
  10. Known 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 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.
Terms in these criteria, in plain language(23)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Allogeneic and autologous transplant

Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

GVHD (graft-versus-host disease)

After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

FEV1

From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
50 participants (estimated)

Study arms

  • Experimental
    Arm 2 - Low-dose

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

    Drug: Pacritinib

  • Experimental
    Arm 3 - High-dose

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

    Drug: Pacritinib

  • Experimental
    Escalating doses of treatment

    Escalating doses of pacritinib to confirm safety in cGVHD

    Drug: Pacritinib

Interventions

  • 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.

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 28 days

  2. Phase II: Overall response rate (ORR)

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

    Time frame: 6 months

Secondary outcomes

  1. Phase I: Pharmacokinetics (PK)

    The secondary endpoint for PK properties includes measures such as AUC, half-life, and steady-state concentration.

    Time frame: every 3 months through up to 12 months of treatment

  2. 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

    Time frame: every 3 months through up to 12 months of treatment

  3. 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

    Time frame: every 3 months through up to 12 months of treatment

07

Study locations

2 of 2 sites recruiting
  • University of Miami
    Miami, Florida 33101, United States
    Recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
    • For more information at the NIH Clinical Center contact National Cancer Institute Referral Office · Contact888-624-1937
08

References and documents

Individual participant data

Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@@@@@@@ All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

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.

09

Updates

2 registry updates since Sep 25, 2026
Minor edits
Nothing that changes what the study is or who can join. Edited: verification date
2 updates, last Nov 6, 2026
Show all 2 updates
  1. Nov 6, 2026
    Minor edits only
    + 1 other change: verification date
  2. Sep 28, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT05531786
Responsible party
Sponsor
First posted
Sep 8, 2022
Start date
Mar 6, 2023
Primary completion
Jul 22, 2027 (estimated)
Completion
Jul 22, 2027 (estimated)
Last update
Nov 6, 2026

Study contacts

Rania S Hishmeh, R.N.
Contact
rania.hishmeh@nih.gov
(240) 858-3681
Najla El Jurdi, M.D.
Contact
najla.eljurdi@nih.gov
(240) 992-4033
Najla El Jurdi, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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