ClinicalTrials.gov record NCT06052618

Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS)

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Aug 22, 2026

Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS)

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
Age18 years old to 120 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This open-label Phase II study tests the oral drug pacritinib in adults with symptomatic KSHV-associated multicentric Castleman disease (KSHV-MCD) or KSHV-associated inflammatory cytokine syndrome (KICS). Participants take pacritinib 200 mg twice daily for up to six 28-day cycles and are monitored with clinic visits, blood tests, heart checks, and imaging. Responses are assessed regularly and there is follow-up after treatment for up to one year.

What it is studying. The study is testing whether pacritinib produces clinical benefit in people with symptomatic KSHV-MCD or KICS, using defined clinical benefit response criteria and regular clinical and radiologic assessments. It also monitors safety and effects on any coexisting Kaposi sarcoma.

What the researchers hope to learn. To evaluate the clinical benefit (response rate) of pacritinib in symptomatic KSHV-MCD and KICS, to assess safety and adverse events, to measure time to treatment failure and duration of benefit, and to observe pacritinib's effect on concurrent Kaposi sarcoma.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Pacritinib

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Participants must meet KSHV-associated Inflammatory Cytokine Syndrome (KICS) criteria or have histologically or cytologically confirmed Kaposi sarcoma herpesvirus -multicentric Castleman disease (KSHV-MCD) confirmed by the CCR, Laboratory of Pathology (LP), NCI
  • Age >= 18 years
  • At least one clinical symptom attributed to KSHV-MCD or KICS, as follows:
  • Intermittent or persistent fever for at least 1 week (>38 degrees C)
  • Fatigue (CTCAE - Grade >=2)
  • Gastrointestinal symptoms (e.g., nausea and anorexia - CTCAE Grade >=1)
  • Respiratory symptoms (e.g., cough and airway hyperreactivity - CTCAE Grade >=1)
  • At least one laboratory abnormality attributed to KSHV-MCD or KICS, as follows:
  • Anemia (hemoglobin [Hgb] 7.0 - 12.5gm/dL)
  • Thrombocytopenia (50,000 - 150,000/mm3)
  • Hypoalbuminemia (<3.4 g/dL)
  • Elevated C-reactive protein [CRP] (>3mg/L)
  • No life or organ-threatening manifestations of KSHV-MCD, KICS or Kaposi Sarcoma (KS)
  • Eastern Cooperative Oncology Group [ECOG] performance status <= 3 (Karnofsky >=60%)
  • Participants must have laboratory parameters as defined below:
  • Total bilirubin <=3 X upper limit of normal (ULN) or <6X ULN for diagnosis of Gilbert's
  • AST(SGOT)/ALT(SGPT) <=2.5 X ULN
  • PT/PTT/INR <=1.5 X ULN
  • Creatinine within normal institutional limits OR Creatinine clearance >=30mL/min/1.73 m\^2 as estimated by either Cockcroft-Gault or 24-hour urine collection for participants with creatinine levels above ULN
  • Participants with HIV should be receiving and willing to continue or willing to initiate an effective antiretroviral therapy (ART) regimen that excludes strong/ moderate CYP3A4 inducer or inhibitors.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, participants must be on suppressive therapy.
  • Participants with a history hepatitis C virus (HCV) infection must have completed treatment with evidence of sustained virologic response for a period of at least 3 months.
  • Participants with KSHV-MCD (Cohort 2) or KICS (Cohort 3) who have received prior therapy, such as rituximab or other monoclonal antibodies, must have a wash out period of at least 3 weeks.
  • Participants receiving medications or substances that are substitutes of strong CYP3A4 inhibitors must have a washout period of at least 5 half-lives of the drug prior to enrollment on study.
  • Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (e.g., intrauterine device [IUD], hormonal [excluding hormonal contraceptives sensitive to CYP3A4 metabolism (i.e. progestin)], surgical sterilization, abstinence) prior to study entry, for the duration of study participation, and for up to 30 days after discontinuation of the study drug.
  • Individuals of child-bearing potential (IOCBP) and individuals able to father a child with a partner able to become pregnant must agree to use a highly effective method of contraception (e.g., intrauterine device [IUD], hormonal [excluding hormonal contraceptives sensitive to CYP3A4 metabolism (i.e. progestin, ethinylestradiol)], surgical sterilization, abstinence) prior to study entry, for the duration of study
  • participation, and for up to 30 days after discontinuation of the study drug. A participant may request that partner uses the highly effective form of contraception to fulfill this requirement.
  • Ability of participant to understand and the willingness to sign a written informed consent document.

Exclusion criteria

  • Grade >2 symptomatic visceral KS (except for edema or non-ulcerating disease restricted to the oral cavity).
  • History of allergic reactions attributed to compounds of similar chemical or biologic
  • composition to pacritinib.
  • Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4. Lists including medications and substances known or with the potential to interact with the specified CYP3A4 isoenzymes.
  • Participants with evidence of ongoing hemorrhage, active signs/symptoms of bleeding, or history of severe bleeding complications in the one year prior to enrollment.
  • Any history of CTCAE Grade >= 3 cardiac events within the last 3 months.
  • QTc(Fredericia) prolongation >480 ms or other factors that increase the risk for QTc prolongation (i.e., heart failure, or a history of long QT interval syndrome).
  • Use of concomitant medications with significant potential for QTc prolongation
  • History of thrombosis, troponin-positive (Tpos) or myocardial infarction within the last 6 months
  • Participants with moderate (Child-Pugh Score B) or severe hepatic impairment (Child-Pugh Score C)
  • Diagnosis of primary effusion lymphoma [PEL] or another lymphoma.
  • Participants with a prior or concurrent malignancy whose natural history or treatment that has potential to interfere with the safety or efficacy assessment of the regimen.
  • Pregnant individuals as evaluated by a positive serum or urine beta-hCG at screening.
  • There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing person with pacritinib. Breastfeeding should be discontinued if the nursing person is treated with pacritinib.
  • Uncontrolled bacterial, mycobacterial, or fungal infection at screening.
  • Uncontrolled intercurrent illness that would limit compliance with study requirements, including results of hematology and chemistry testing, infection disease (etc.)

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

Background:

  • Pacritinib, is a JAK2/tyrosine kinase 3 inhibitor with negligible activity against JAK1 that also suppresses the interleukin-1 (IL-1) directed inflammatory pathway via inhibition of interleukin 1 receptor associated kinase.
  • Phase III studies of patients with myelofibrosis treated with pacritinib have demonstrated safety and efficacy as compared with best available treatment.
  • Pacritinib at 200mg twice daily emerged as the recommended dose in the treatment of myelofibrosis.
  • Through its activity on JAK2 and IRAK1, pacritinib blocks signaling through the interleukin 6 receptor (IL-6R); this should also include signaling through gp130 mediated by KSHV vIL-6.
  • In preliminary unpublished results, the Yarchoan lab has found that pacritinib is highly active against primary effusion lymphoma (PEL) cells in vitro. PEL is caused by Kaposi sarcoma associated herpesvirus (KSHV), and most PEL affected patients are co-infected with Epstein- Barr virus (EBV). Like the plasmablasts of KSHV- multicentric Castleman disease (MCD), PEL cells are KSHV-infected B cells and thus can be a model for KSHVMCD.
  • Given the overlapping cytokine profile between KSHV-MCD and KSHV-associated inflammatory cytokine syndrome (KICS) and elevated levels of IL6, we expect that pacritinib will have therapeutic effect in this disorder that is associated with excess inflammation.

Objective: -To evaluate the clinical benefit of pacritinib in participants with symptomatic KSHV-MCD or KICS using a modified KSHV-MCD/KICS Clinical Benefit Response Criteria Eligibility:

  • Pathologically confirmed MCD or evidence of KICS
  • Age >= 18
  • At least one clinical symptom and at least one laboratory attributable to KSHV-MCD or KICS
  • ECOG performance status <= 3
  • No life- or organ-threatening manifestations of MCD or KICS
  • No concurrent diagnosis of PEL
  • No symptomatic pulmonary or visceral Kaposi Sarcoma (KS)

Design:

  • Open label, single center pilot Phase II study. Eligible participants receive pacritinib orally 200mg twice daily until progression or up to 6 cycles.
  • Participants will be divided by prior therapy for KSHV-MCD (no prior therapy or prior therapy) and by diagnosis of KICS.
  • KICS and KSHV-MCD responses will be evaluated by KSHV-MCD Clinical Benefit Response Criteria every 4 weeks.
  • Interruptions to pacritinib will be permissible for treatment of worsening KS that develops on study and such interruptions may last up to 12 weeks.
  • Radiological assessment using PET-CT and CT will be used to assess response at 1, 3 and 6 months on study.
  • Total maximum number of evaluable participants is 54.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants undergo screening with a physical exam, blood tests, heart testing, and imaging scans. They will take oral pacritinib 200 mg twice daily for up to six 28‑day cycles and record each dose in a diary. Early visits occur three times in the first 4 weeks then usually every 4 weeks; saliva samples will be collected and participants may be asked to allow optional skin or lymph node tissue sampling. Those with Kaposi sarcoma may require bronchoscopy and/or endoscopy; after the last dose there are safety visits at 7 and 30 days and then clinic visits every 3 months for up to 1 year; pacritinib may be interrupted for worsening KS (interruptions up to 12 weeks allowed).

How the study is structured. Open-label, single-group Phase II trial. All participants receive pacritinib 200 mg by mouth twice daily for up to six 28-day cycles. Participants have initial screening, frequent clinic visits early on (three visits in the first four weeks) then roughly monthly visits with blood tests, heart function checks, imaging (including PET-CT/CT), symptom assessments, and saliva samples; some may have optional tissue sampling. Treatment responses are checked every four weeks; there are safety visits shortly after stopping drug and clinic follow-up every three months for up to one year. Interruptions for worsening Kaposi sarcoma are permitted for specified periods.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Castleman disease

Clinical trials14 trials listed for Castleman diseaseEvery trial the registry lists for Castleman disease, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Castleman disease researchLatest monthly update: September 2026. Includes: Unicentric tumor removal. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Mar 17, 2025
Primary completion
Jan 1, 2033 (estimated)
Study completion
Jan 1, 2034 (estimated)
Target enrollment
75 participants (estimated)
Last updated on registry
Aug 24, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
National Cancer Institute (NCI)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
ECOG
A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
Karnofsky
A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
upper limit of normal
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
Creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
Cohort
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
prior therapy
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
washout period
A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
5 half-lives
The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
study drug
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
QTc
A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
concomitant medications
Other medicines a participant takes during the study. Some must be reported; some are restricted.
natural history
A study that follows how a condition changes over time without assigning an experimental treatment. It may involve study visits and tests, and is often used to plan future trials.
at screening
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
adverse events
Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
INCLUSION CRITERIA
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
EXCLUSION CRITERIA
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Phase III
A later-stage study, usually with more participants, designed to give stronger evidence about how well a treatment works and how safe it is. It often compares the treatment with standard care or a placebo, and results may support an application for approval.
Open label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
PET
A scan in which a small amount of a radioactive tracer is injected so that activity in tissues can be seen. Often combined with a CT or MRI scan.
CT
An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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