Pacritinib for Castleman Disease and Syndrome

Overseen By National Cancer Institute Referral Offic

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Antiretrovirals, HBV suppressive therapy

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Visceral KS, Cardiac conditions, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 11

Duration: 24 weeks

65 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Kaposi sarcoma herpesvirus (KSHV)-associated inflammatory cytokine syndrome (KICS) and KSHV-multicentric Castleman disease (MCD) occur in people living with HIV. These diseases cause severe inflammation that can be fatal if not treated. Objective: To test a drug (pacritinib) in people with KSHV-associated KICS or MCD. Eligibility: People aged 18 years and older with KSHV-associated KICS or MCD. They must have at least one symptom. Design: Participants will be screened. They will have a physical exam with blood tests and tests of their heart function. They will have imaging scans. Their ability to perform everyday tasks will be reviewed. In some participants who have Kaposi sarcoma (KS) with KICS or MCD, these individuals may need a bronchoscopy and/or endoscopy of the upper or lower intestine: A flexible tube with a camera and a light source will be inserted through the mouth or anus to see these structures and assess any KS. Pacritinib is a capsule taken by mouth. Participants will take the drug twice a day, every day, for up to 24 weeks. They will write down each dose in a diary. Participants will visit the clinic 3 times in the first 4 weeks. Their visits will taper to once every 4 weeks. Imaging scans, blood tests, and other tests will be repeated during these visits. Participants will give samples of saliva. They may opt to allow tissues samples to be taken from their skin and lymph nodes. Participants will have follow-up visits 7 days and 30 days after their last dose of pacritinib. After that, they will visit the clinic every 3 months for up to 1 year. The physical exam and blood, heart, and imaging tests will be repeated at these visits.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 3 weeks for those who have received prior therapy like rituximab, and at least 5 half-lives for medications that are strong CYP3A4 inhibitors. Participants with HIV should continue their antiretroviral therapy, but it must exclude strong/moderate CYP3A4 inducers or inhibitors.

Is pacritinib safe for human use?

Pacritinib has been studied in several clinical trials for conditions like myelofibrosis, showing an acceptable safety profile. The most common side effects are mild to moderate stomach issues, and there are measures in place to reduce risks of heart and bleeding problems. ^{1 2 3 4 5}

Research Team

Ramya M Ramaswami, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with KSHV-associated inflammatory cytokine syndrome or multicentric Castleman disease, who have symptoms like fever and fatigue, and lab abnormalities such as anemia. They must not be severely ill from these conditions, have good heart function, agree to use contraception if applicable, and can't be on certain drugs that affect pacritinib.

Inclusion Criteria

I am 18 years old or older.

I can take care of myself but may not be able to do active work.

People of child-bearing potential and those who can father children must agree to use adequate contraception (hormonal or barrier method of birth control) prior to treatment initiation and for the duration of study participation and for 3 months after the last dose

Exclusion Criteria

Pregnant individuals as evaluated by a positive serum or urine beta-hCG at screening

Uncontrolled intercurrent illness that would limit compliance with study requirements, including results of hematology and chemistry testing, infection disease (etc.)

I have Kaposi's sarcoma with symptoms, not just in my mouth.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pacritinib orally 200mg twice daily for up to 24 weeks

24 weeks

3 visits in the first 4 weeks, then once every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Follow-up visits 7 days and 30 days after last dose, then every 3 months

Treatment Details

Interventions

• Pacritinib

Trial Overview The trial is testing the effectiveness of Pacritinib for treating severe inflammation in HIV-positive individuals with either KICS or MCD. Participants will take Pacritinib orally twice daily for up to 24 weeks and attend regular clinic visits for monitoring through physical exams, blood tests, imaging scans, and possibly tissue samples.

Participant Groups

Group I: Arm 1 Experimental Treatment 1 Intervention

Treatment with pacritinib

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

Pacritinib was found to be well tolerated in patients with myelofibrosis, with a maximum tolerated dose established at 500 mg once daily and a recommended phase 2 dose of 400 mg once daily, showing manageable side effects and a low incidence of severe myelosuppression.

In the phase 2 part of the study, 23.5% of patients achieved a significant reduction in spleen volume after 24 weeks, indicating clinical activity, while 38.9% reported improved quality of life, highlighting its potential as an effective treatment for myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. Verstovsek, S., Odenike, O., Singer, JW., et al.[2022]

Pacritinib, particularly at a dose of 200 mg twice per day, showed significant efficacy in treating advanced myelofibrosis in patients who were intolerant or resistant to ruxolitinib, with a spleen volume response rate of 9.3%.

The study demonstrated an acceptable safety profile for pacritinib, with no increase in severe hemorrhagic or cardiac events at the highest dose, making it a promising option for patients with severe thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. Gerds, AT., Savona, MR., Scott, BL., et al.[2021]

Pacritinib is a selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3, showing potential for treating blood cancers like myeloproliferative neoplasias and acute myeloid leukemia, with strong antiproliferative effects and the ability to induce cell death.

In early-phase clinical trials, pacritinib demonstrated promising efficacy and an acceptable safety profile, with mild to moderate gastrointestinal issues being the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of pacritinib and its potential in the treatment of hematologic disorders. Hatzimichael, E., Tsolas, E., Briasoulis, E.[2022]

Pacritinib (VONJO™) is an oral kinase inhibitor approved in February 2022 for treating adults with intermediate- or high-risk myelofibrosis who have low platelet counts (below 50 × 10^9/L).

The approval was based on the phase III PERSIST-2 trial, which showed that pacritinib effectively reduced spleen volume in patients, indicating its efficacy in managing symptoms of myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pacritinib: First Approval. Lamb, YN.[2022]

Pacritinib is a potent inhibitor of JAK2 and FLT3 that shows clinical efficacy in treating myelofibrosis without causing myelosuppression, which is a common side effect of other JAK inhibitors.

The drug selectively inhibits JAK2 while sparing JAK1, and it also reduces harmful cytokines, suggesting potential therapeutic benefits in other blood cancers and inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. Singer, JW., Al-Fayoumi, S., Ma, H., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of pacritinib, a next generation JAK2/FLT3 inhibitor, in myelofibrosis or other myeloid malignancies. [2022]

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

Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis. [2021]

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

Profile of pacritinib and its potential in the treatment of hematologic disorders. [2022]

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

Pacritinib: First Approval. [2022]

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

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. [2022]