Pacritinib for Chronic Graft-versus-Host Disease

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

Trial Summary

What is the purpose of this trial?

This trial tests pacritinib, a capsule taken by mouth, in adults with moderate or severe chronic graft-versus-host disease (cGVHD) that hasn't responded to other treatments. Pacritinib helps by blocking proteins that cause inflammation and immune issues. Participants will take the drug regularly and have periodic check-ups over an extended period.

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.

How is the drug Pacritinib unique for treating 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 to fight cancer. Unlike other treatments, it spares certain immune cells (iTregs) and promotes a specific immune response (Th2), potentially offering a different approach to managing the disease. ^{1 2 3 4 5}

Research Team

Najla El Jurdi, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Australia pubmed.ncbi.nlm.nih.gov

ANZTCT consensus position statement on ruxolitinib in steroid-refractory acute and chronic graft-versus-host disease. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

New Indication for Ruxolitinib. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

The Effectiveness of Ruxolitinib for Acute/Chronic Graft-versus-Host Disease in Children: A Retrospective Study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. [2018]