Graft vs Host DiseasePhase 1/2NCT05531786
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 study testing Pacritinib in people with Graft vs Host Disease, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Graft vs Host Disease
- What is being tested?
- Pacritinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Mar 2023to 22 Jul 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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).
- Participants with the following cardiac conditions at screening:
- symptomatic congestive heart failure
- unstable angina pectoris
Show all 19Show fewer
- 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.
- Pregnancy or breastfeeding.
- Participants with any active, uncontrolled viral, bacterial, or fungal infection are excluded.
- Other malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix or breast which requires active treatment.
- Uncontrolled intercurrent illness evaluated by history, physical exam and chemistries or situation that would limit compliance with study requirements.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact National Cancer Institute Referral Office, 888-624-1937
- Recruiting
University of Miami
Miami, Florida, 33101
About this study
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.
Read more
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.
- Conditions
- Graft vs Host Disease
- Being tested
- Pacritinib
- Keywords
- Anti-Inflammatory, Fibrosis, Inflammation, Refractory, Systemic Therapy
- Medical subject headings
- Graft vs Host Disease, Fibrosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PacritinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 2 - Low-dose | Experimental | Expansion dosing to evaluate the efficacy of pacritinib 100 mg PO BID Receives: Drug: Pacritinib |
| Arm 3 - High-dose | Experimental | Expansion dosing to evaluate the efficacy of pacritinib 200 mg PO BID Receives: Drug: Pacritinib |
| Escalating doses of treatment | Experimental | Escalating doses of pacritinib to confirm safety in cGVHD Receives: Drug: Pacritinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 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.
Measured: 6 months
Secondary outcomes (3)
Phase I: Pharmacokinetics (PK)
The secondary endpoint for PK properties includes measures such as AUC, half-life, and steady-state concentration.
Measured: every 3 months through up to 12 months of treatment
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
Measured: every 3 months through up to 12 months of treatment
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
Measured: every 3 months through up to 12 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study start6 Mar 2023
- Primary completion22 Jul 2027 (estimated)
- Study completion22 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Najla El Jurdi, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05531786
- Sponsor's protocol ID
- 10000643
- Other IDs
- 000643-C
- Status last verified
- 30 Oct 2026
- First submitted
- 3 Sep 2022
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05531786
- Acronym / sponsor ID
- 10000643
- Conditions
- Graft vs Host Disease
- Keywords
- Anti-Inflammatory, Fibrosis, Inflammation, Refractory, Systemic Therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 6 Mar 2023 (actual)
- Primary completion
- 22 Jul 2027 (estimated)
- Study completion
- 22 Jul 2027 (estimated)
- First posted
- 8 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 2 - Low-dose | Experimental | Drug: PacritinibExpansion dosing to evaluate the efficacy of pacritinib 100 mg PO BID |
| Arm 3 - High-dose | Experimental | Drug: PacritinibExpansion dosing to evaluate the efficacy of pacritinib 200 mg PO BID |
| Escalating doses of treatment | Experimental | Drug: PacritinibEscalating doses of pacritinib to confirm safety in cGVHD |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (19 listed)
- 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).
- Participants with the following cardiac conditions at screening:
- Left ventricular ejection fraction <= 50% by transthoracic echocardiogram (TTE) at screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PacritinibPacritinib 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. | Drug | Arm 2 - Low-dose, Arm 3 - High-dose, Escalating doses of treatment |
Primary outcome
Phase I: Safety of pacritinib in refractory cGVHD.
Time frame: 28 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)
Time frame: 6 months
the fraction with clinical responses reported separately by arm, with a separate 95% confidence interval for each cohort.
3 secondary outcomes
Phase I: Pharmacokinetics (PK)
Time frame: every 3 months through up to 12 months of treatment
Phase 2: Safety
Time frame: every 3 months through up to 12 months of treatment
Phase 2: Clinical outcomes
Time frame: every 3 months through up to 12 months of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Najla El Jurdi, M.D. principal investigator
National Cancer Institute (NCI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pacritinib in people with Graft vs Host Disease, run by National Cancer Institute (NCI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rania S Hishmeh, R.N. ((240) 858-3681, rania.hishmeh@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Safety of pacritinib in refractory cGVHD. (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.