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

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called pacritinib for individuals with conditions linked to the Kaposi sarcoma herpesvirus (KSHV) and HIV. These conditions, KSHV-associated inflammatory cytokine syndrome (KICS) and KSHV-multicentric Castleman disease (MCD), cause severe inflammation and can be life-threatening without proper treatment. The trial seeks participants with KSHV-associated KICS or MCD who experience at least one symptom, such as persistent fever, fatigue, or respiratory issues. Participants will take pacritinib orally twice a day for up to 24 weeks and attend regular clinic visits for monitoring and testing. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that pacritinib is likely to be safe for humans?

Research has shown that pacritinib has been tested for conditions like myelofibrosis and generally has a safe track record. The most common side effects include diarrhea, low platelet count (thrombocytopenia), nausea, anemia, and swelling in the limbs (peripheral edema). These side effects occurred in more than 20% of patients in past studies.

The FDA has already approved pacritinib for treating myelofibrosis, a disorder affecting bone marrow, indicating it is usually well-tolerated by people with this condition. While this does not guarantee the same safety for KSHV-related conditions, it offers some reassurance about its overall safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about pacritinib for Castleman Disease and Syndrome because it offers a novel approach by targeting the JAK2 pathway, which is different from the standard treatments like corticosteroids and chemotherapy. While most current options focus on controlling symptoms and inflammation broadly, pacritinib is designed to specifically inhibit the enzymes involved in the disease process. This targeted mechanism could potentially offer more effective control of the disease with fewer side effects, making it a promising option for patients.

What evidence suggests that pacritinib might be an effective treatment for KSHV-associated KICS or MCD?

Studies have shown that pacritinib can effectively treat diseases linked to KSHV, such as multicentric Castleman disease (MCD). Research from the Yarchoan lab demonstrated that pacritinib effectively stops the growth of primary effusion lymphoma (PEL) cells in lab tests. Given the similarities between PEL and MCD, pacritinib might also work well for MCD. Pacritinib has successfully treated myelofibrosis at a dose of 200 mg twice a day, increasing confidence in its potential effectiveness. These findings suggest that pacritinib could help manage symptoms and inflammation in conditions related to KSHV. Participants in this trial will receive pacritinib to evaluate its effectiveness for Castleman Disease and Syndrome. ^{1 2 3 6 7}

Who Is on the Research Team?

Ramya M Ramaswami, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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 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

Ability of participant to understand and the willingness to sign a written informed consent document

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06052618

Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus ... In preliminary unpublished results, the Yarchoan lab has found that pacritinib is highly active against primary effusion lymphoma (PEL) cells in vitro. PEL is ...

2. withpower.com withpower.com/trial/phase-2-sarcoma-kaposi-8-2023-6d332

Pacritinib for Castleman Disease and Syndrome Pacritinib, particularly at a dose of 200 mg twice per day, showed significant efficacy in treating advanced myelofibrosis in patients who were intolerant or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10876599/

Pacritinib inhibits proliferation of primary effusion ... We explored the potential of JAK inhibitors for use in PEL and KSHV-MCD, and found that pacritinib was superior to others in inhibiting the growth of PEL cell ...

4. healthscout.app healthscout.app/trial_match/view_trial/NCT06052618/?back=/trial_match/view_trials/condition/sarcoma/%3Fpage%3D5

Trial: Phase II Study of Pacritinib in Kaposi … - HealthScout Preclinical data from NCI suggest activity against KSHV-driven primary effusion lymphoma cells, providing rationale for targeting the inflammatory cytokine ...

5. synapse.patsnap.com synapse.patsnap.com/disease/c19378950b7843d5a72e5d59e67995c9

Castleman Disease - Drugs, Targets, Patents These updated results show promising efficacy and safety data of orelabrutinib in prior BTKi-intolerant iNHL patients. As data cutoff (July 9, 2024), 66 ...

6. croiconference.org croiconference.org/wp-content/uploads/sites/2/posters/2023/CROI2023-Poster-630-133210049895663618.pdf

Rationale for The Use of Pacritinib in KSHV-Multicentric ... Rationale for The Use of Pacritinib in KSHV-Multicentric Castleman Disease. CONCLUSIONS. • Pacritinib inhibited cell growth in PEL lines. • It also ...

7. vonjohcp.com vonjohcp.com/

VONJO® (pacritinib) HCP: VONJO® for Myelofibrosis Treatment In PERSIST-2, the most common adverse reactions in ≥20% of patients (n=106) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. Learn more ...