Pacritinib for Chronic Graft-versus-Host Disease

Recruiting at 1 trial location

Overseen By Najla El Jurdi, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Ruxolitinib, Ibrutinib, CYP3A4 inducers

Disqualifiers: Active HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 6-12 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called pacritinib for individuals with chronic graft-versus-host disease (cGVHD), a condition that can develop after a stem cell transplant when donor cells attack the recipient's body. The goal is to determine if pacritinib can help those whose cGVHD hasn’t improved with at least two other treatments. The trial seeks participants with moderate or severe cGVHD that hasn't responded to previous therapies. Participants will take pacritinib capsules at home and attend regular clinic visits for monitoring. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but if you are on systemic therapy for cGVHD, you need to be on a stable or tapering dose for the 4 weeks before joining. Also, you must stop using strong CYP3A4 inducers or inhibitors 2 weeks before starting the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pacritinib may be both effective and safe for individuals with multi-refractory chronic graft-versus-host disease (cGVHD). In studies, pacritinib demonstrated a good safety record. While some participants experienced side effects, most tolerated the treatment well. Additionally, studies found that pacritinib, when combined with other drugs, remained safe, suggesting that pacritinib alone could also be safe. Consider these findings and consult your healthcare provider to determine if joining the trial is appropriate for you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cGVHD?

Pacritinib is unique because it targets chronic graft-versus-host disease (cGVHD) differently from standard treatments like corticosteroids and immunosuppressants. Unlike these traditional options, pacritinib is a selective JAK2 inhibitor, which means it specifically blocks a key pathway involved in inflammation and immune response. This targeted approach could offer a more precise way to manage cGVHD, potentially reducing side effects associated with broader immunosuppression. Researchers are also exploring different dosing strategies, including high-dose and low-dose regimens, to find the most effective and safe way to use pacritinib for this condition.

What evidence suggests that pacritinib might be an effective treatment for chronic graft-versus-host disease?

Research has shown that pacritinib may help treat chronic graft-versus-host disease (cGVHD). In one study, 67% of patients who didn't respond to other treatments improved after six months of using pacritinib. This trial will evaluate different dosing strategies of pacritinib, including low-dose, high-dose, and escalating doses, to assess its efficacy and safety in cGVHD. Pacritinib blocks JAK2, a protein involved in the immune system that contributes to cGVHD. By blocking JAK2, pacritinib might reduce the disease while still allowing the immune system to function. These findings suggest pacritinib could be a helpful option for those dealing with cGVHD. ^{1 3 5 6 7}

Who Is on the Research Team?

Najla El Jurdi, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with moderate or severe chronic graft-versus-host disease (cGVHD) after stem cell transplant, which hasn't improved after at least two treatments. They must be in remission from their primary cancer for three months and have good organ function. Participants should not have acute GVHD, active infections like HIV or hepatitis, recent use of certain drugs, other cancers needing treatment, or be pregnant/breastfeeding.

Inclusion Criteria

I have moderate or severe chronic GVHD after a stem cell transplant.

I agree to use effective birth control during and 30 days after the study.

I am on a stable or decreasing dose of medication for cGVHD.

Exclusion Criteria

I do not have serious heart conditions like heart failure or irregular heartbeats.

I have active acute GVHD without signs of chronic GVHD.

Concurrent treatment with any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take pacritinib orally once or twice daily in 28-day cycles, with clinic visits every 2 weeks for the first 4 months, then every 4 weeks

6-12 months

8 visits (in-person) in the first 4 months, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits continuing for up to 2 years

up to 2 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pacritinib

Trial Overview

The trial is testing Pacritinib's effectiveness on patients with cGVHD who haven't responded to previous therapies. It involves taking the drug daily at home and attending regular clinic visits for tests and questionnaires about quality of life. The study may last up to a year with follow-up visits extending another year.

How Is the Trial Designed?

Group I: Escalating doses of treatment Experimental Treatment 1 Intervention

Escalating doses of pacritinib to confirm safety in cGVHD

Group II: Arm 3 - High-dose Experimental Treatment 1 Intervention

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

Group III: Arm 2 - Low-dose Experimental Treatment 1 Intervention

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

Pacritinib is already approved in United States for the following indications:

Approved in United States as Vonjo for:

• Intermediate or high-risk primary or secondary myelofibrosis with platelet counts below 50 × 10^9/L

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ruxolitinib is highlighted as an effective treatment option for patients with corticosteroid-refractory and corticosteroid-dependent graft-versus-host disease (GvHD), targeting the JAK1 and JAK2 pathways.

The paper provides a comprehensive overview of both acute and chronic GvHD management, emphasizing the importance of innovative therapies like ruxolitinib in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ANZTCT consensus position statement on ruxolitinib in steroid-refractory acute and chronic graft-versus-host disease. Hamad, N., Bilmon, I., Chee, L., et al.[2023]

In a study of 115 patients with steroid-refractory or -dependent chronic graft versus host disease (cGVHD), ruxolitinib demonstrated an overall response rate of approximately 48.6% at 3 months, indicating its efficacy in a heavily pretreated population.

After 12 months of treatment, 37.9% of patients were able to discontinue prednisone, and 63.8% could taper their dosage to less than 0.1 mg/kg, highlighting ruxolitinib's potential to reduce steroid dependency in cGVHD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure. White, J., Elemary, M., Linn, SM., et al.[2023]

Ruxolitinib (Jakafi) has received approval for the treatment of chronic graft-vs-host disease, indicating its efficacy in managing this condition.

The approval of ruxolitinib highlights its role as a kinase inhibitor, which works by targeting specific pathways involved in the immune response, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Ruxolitinib. Aschenbrenner, DS.[2023]

JAK2 plays a crucial role in graft-versus-host disease (GVHD), and using JAK2-deficient T cells can reduce GVHD while preserving the beneficial graft-versus-leukemia effect, suggesting a potential therapeutic strategy.

Pacritinib, a JAK2 inhibitor, has been shown to significantly reduce GVHD and maintain antitumor immunity in rodent models, and it is currently being tested in a clinical trial for preventing acute GVHD after hematopoietic cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. Betts, BC., Bastian, D., Iamsawat, S., et al.[2018]

In a study of 53 pediatric patients with graft-versus-host disease (GVHD), ruxolitinib demonstrated a high overall response rate of 75.5%, with 80.6% efficacy in chronic GVHD (cGVHD) cases compared to 64.7% in acute GVHD (aGVHD).

Ruxolitinib treatment allowed 39% of patients to discontinue steroids and 22.2% to reduce their steroid dosage, although it was associated with a high incidence of adverse events (94.1%) in the aGVHD group, indicating a need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Ruxolitinib for Acute/Chronic Graft-versus-Host Disease in Children: A Retrospective Study. Yang, W., Zhu, G., Qin, M., et al.[2022]

Citations

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Pacritinib Elicits Early Responses in Multi-Refractory ...

Pacritinib demonstrated a 67% overall response rate at 6 months in multi-refractory cGVHD patients, with no dose-limiting toxicities reported.

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targetedonc.com

targetedonc.com/view/pacritinib-sirolimus-and-tacrolimus-combo-fails-to-improve-gvhd-outcomes

Pacritinib, Sirolimus, and Tacrolimus Combo Fails to ...

A phase 2 study found that a combination of pacritinib, sirolimus, and tacrolimus successfully suppressed pSTAT3 and Th1/Th17 cells, but failed to prevent ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8127396/

Pacritinib combined with sirolimus and low-dose tacrolimus for ...

In this first-in-human, phase I, graft-versus-host disease (GVHD) prevention trial (NCT02891603) we combine pacritinib (PAC), a JAK2 inhibitor, with sirolimus ...

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roswellpark.org

roswellpark.org/newsroom/202408-final-results-phase-2-clinical-trial-clarify-role-jak2-inhibitor-combating-acute

Final Results of Phase 2 Clinical Trial Clarify Role of JAK2 ...

Study added pacritinib to standard sirolimus/tacrolimus regimen · JAK2 inhibition + reducing Th1/Th17 cells does not improve GVHD prevention ...

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withpower.com

withpower.com/trial/phase-2-graft-vs-host-disease-8-2022-7aba1

Pacritinib for Chronic Graft-versus-Host Disease

Pacritinib is unique because it is a multikinase inhibitor that targets JAK2, which helps reduce graft-versus-host disease while maintaining the body's ability ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05531786?cond=Stem+Cell&aggFilters=status%3A

Phase I/II Study of Pacritinib, A JAK2/IRAK1/CSF1R Inhibitor, in ...

An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

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prnewswire.com

prnewswire.com/news-releases/phase-1-trial-demonstrates-encouraging-clinical-benefit-and-promising-safety-profile-of-pacritinib-for-the-prevention-of-graft-versus-host-disease-published-in-clinical-cancer-research-301252886.html

Phase 1 Trial Demonstrates Encouraging Clinical Benefit ...

The results demonstrated that pacritinib, combined with sirolimus and low-dose tacrolimus (PAC/SIR/TAC), has a promising safety profile and ...