Pacritinib for Castleman Disease and Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Ramya M Ramaswami, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 1 Jurisdiction

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.

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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.

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

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] Pacritinib (SB1518) is a highly selective kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CFS1R. This multicenter phase 1/2 study evaluated the maximum tolerated dose (MTD), safety, and clinical activity of pacritinib in patients with myelofibrosis (MF) and other advanced myeloid malignancies.

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] PAC203 is a randomized dose-finding study of pacritinib, an oral JAK2/IRAK1 inhibitor, in patients with advanced myelofibrosis who are intolerant of or resistant to ruxolitinib. Patients were randomized 1:1:1 to pacritinib 100 mg once per day, 100 mg twice per day, or 200 mg twice per day. Enhanced eligibility criteria, monitoring, and dose modifications were implemented to mitigate risk of cardiac and hemorrhagic events. Efficacy was based on ≥35% spleen volume response (SVR) and ≥50% reduction in the 7-component total symptom score (TSS) through week 24. Of 161 patients, 73% were intolerant of and 76% had become resistant to ruxolitinib; 50% met criteria for both. Severe thrombocytopenia (platelet count

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

Profile of pacritinib and its potential in the treatment of hematologic disorders. [2022] Pacritinib (previously known as SB-1518) is an innovative selective inhibitor of Janus kinase 2 and FMS-related tyrosine kinase 3 providing potential in the treatment of hematological malignancies such as myeloproliferative neoplasias, acute myeloid leukemia, and various lymphomas. Pacritinib has potent antiproliferative activity in Janus kinase 2 and/or FMS-related tyrosine kinase 3 activity-dependent cell lines and an ability to promote apoptosis and inhibit the signal transducers and activators of transcription (STAT) pathway. Pharmacokinetic studies have indicated a good per os bioavailability and favorable kinetic parameters. To date, promising results have been produced in five completed early-phase clinical trials in which pacritinib has been studied. Pacritinib displayed interesting activity and an acceptable safety profile, with mild to moderate gastrointestinal disorders being its most common adverse effects.

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

Pacritinib: First Approval. [2022] Pacritinib (VONJO™) is an orally administered, small molecule kinase inhibitor being developed by CTI BioPharma for the treatment of myelofibrosis and graft-versus-host disease. Pacritinib received its first approval in February 2022 in the USA for the treatment of adults with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L. The accelerated approval was based on results from the randomized, active-controlled, phase III PERSIST-2 trial, in which spleen volume reduction was demonstrated in pacritinib recipients. This article summarizes the milestones in the development of pacritinib leading to this first approval for myelofibrosis.

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

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. [2022] Pacritinib, potent inhibitor of Janus kinase 2 (JAK2), JAK2V617F, and fms-like receptor tyrosine kinase 3, is in Phase III development in myelofibrosis. Among type 1 inhibitors, pacritinib shows a lack of myelosuppression at doses that both inhibit JAK2/signal transducer and activator of transcription 3 pathway and demonstrate clinical efficacy. To elucidate these mechanisms and identify other disease targets, a kinome analysis screened 439 recombinant kinases at 100 nM pacritinib concentration. For kinases with >50% inhibition, pacritinib was titrated from 1 to 100 nM. JAK2, JAK2V617F, FLT3, colony-stimulating factor 1 receptor, and interleukin-1 receptor-associated kinase 1 achieved half-maximal inhibitory concentrations