What side effects are associated with this type of intervention?

Common treatments for Graft-versus-Host Disease (GVHD), including JAK2 inhibitors like Pacritinib, often have side effects such as cytopenias (low blood cell counts), gastrointestinal symptoms (nausea, diarrhea), and liver enzyme abnormalities. Other treatments, such as corticosteroids and immunosuppressive agents, can increase the risk of infections, hypertension, hyperglycemia, and bone density loss.

What prior FDA approvals exist?

The FDA has approved several treatments for Graft-versus-Host Disease (GVHD), including JAK inhibitors similar to Pacritinib. Ruxolitinib, another JAK1/2 inhibitor, was approved for steroid-refractory acute GVHD in 2019. Additionally, ibrutinib, a Bruton's tyrosine kinase inhibitor, was approved for chronic GVHD in 2017. These approvals highlight the role of targeted therapies in managing GVHD, particularly for patients who do not respond to conventional treatments.

What other types of research exist?

Promising alternatives to Pacritinib for treating Graft-versus-Host Disease in 2024 include Ruxolitinib, which is another JAK1/2 inhibitor with proven efficacy in GVHD. Additionally, novel therapies such as Itacitinib (a selective JAK1 inhibitor) and Belumosudil (a ROCK2 inhibitor) have shown promise in clinical trials for GVHD patients.

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JAK2/IRAK1/CSF1R Inhibitor

Pacritinib for Chronic Graft-versus-Host Disease

Phase 1 & 2

Recruiting

Led By Noa G Holtzman, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every 3 months through up to 12 months of treatment

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects are not listed here, participants will be monitored closely for any adverse reactions due to Pacritinib throughout the trial period during their regular clinic visits.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ every 3 months through up to 12 months of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~every 3 months through up to 12 months of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and every 3 months through up to 12 months of treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase I: Safety of pacritinib in refractory cGVHD.

Phase II: Overall response rate (ORR)

Secondary study objectives

Phase 2: Clinical outcomes

Phase 2: Safety

Phase I: Pharmacokinetics (PK)

Side effects data

From 2022 Phase 1 & 2 trial • 40 Patients • NCT02891603

70%

Diarrhea

50%

Febrile neutropenia

50%

Dehydration

50%

Anorexia

40%

Mucositis oral

30%

Rash maculo-papular

30%

Nausea

30%

Fatigue

30%

Hypertension

20%

Colitis

20%

Neutrophil count decreased

20%

Alanine aminotransferase increased

20%

Platelet count decreased

20%

Abdominal pain

20%

Skin infection

20%

C Diff

20%

Pain in extremity

10%

Oral pain

10%

Edema trunk

10%

Pain of skin

10%

Soft tissue infection

10%

Oral fungus

10%

Sinusitis

10%

Anemia

10%

Creatinine increased

10%

Rectal pain

10%

Ileus

10%

Vomiting

10%

Aspartate aminotransferase increased

10%

Hyponatremia

10%

CMV+

10%

Electrocardiogram QT corrected interval prolonged

10%

Periorbital edema

10%

Anaphylaxis

10%

Headache -migraine

10%

Abdominal Pain

10%

Metabolism and nutrition disorders - Other

10%

Acute GVHD of skin

10%

Urticaria

10%

Metabolism and Nutrition disorders - Other

10%

Edema limbs

10%

Hypotension

10%

Thromboembolic event

10%

Hypoxia

10%

Insomnia

10%

Anxiety

10%

Hallucinations

10%

Headache

10%

Cardiac disorders - Other

10%

Allergic reaction

100%

80%

60%

40%

20%

Study treatment Arm

Phase 1, Level 1: Pacritinib With Sirolimus and Tacrolimus

Phase 1, Level 2: Pacritinib With Sirolimus and Tacrolimus

Phase 2: Pacritinib With Sirolimus and Tacrolimus

Trial Design

3Treatment groups

Experimental Treatment

Group I: Escalating doses of treatmentExperimental Treatment1 Intervention

Escalating doses of pacritinib to confirm safety in cGVHD

Group II: Arm 3 - High-doseExperimental Treatment1 Intervention

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

Group III: Arm 2 - Low-doseExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pacritinib

2017

Completed Phase 2

~330

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Graft-versus-Host Disease (GVHD) include Janus Kinase 2 (JAK2) inhibitors like Pacritinib, which work by blocking the JAK-STAT signaling pathway that is crucial for the activation and proliferation of T cells. This inhibition helps reduce the immune response that causes GVHD. Other treatments include corticosteroids, which suppress the overall immune response, and calcineurin inhibitors like cyclosporine and tacrolimus, which inhibit T-cell activation. These treatments are vital for GVHD patients as they help control the overactive immune response, thereby reducing tissue damage and improving patient outcomes.

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