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

NCT06052618 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001537001537-C
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

KSHV Inflammatory Cytokine Syndrome (KICS); Kaposi Sarcoma Herpesvirus -Associated Multicentric Castleman Disease

Keywords

JAK2; Interleukin-1; interleukin 6 receptor; Lymphoproliferative Disorder; HIV

Outcome Measures

Primary Outcomes (1)

• Clinical benefit

  Percentage of participants with the best overall response of CR or PR to therapy.

  Prior to each cycle and at EOT and 1 year post treatment

Secondary Outcomes (3)

• Safety of pacritinib

  Prior to each cycle, at EOT, and safety visit.

• Time to treatment failure and duration of benefit

  Prior to each cycle and at EOT and 1 year post treatment

• Effect of pacritinib on concurrent diagnosis of Kaposi sarcoma (KS)

  Prior to each cycle

Study Arms (1)

Arm 1

EXPERIMENTAL

Treatment with pacritinib

Drug: Pacritinib

Interventions

Pacritinib DRUG

Pacritinib is administered orally as 200 mg twice daily for a total of 6, 28-day cycles

Arm 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoproliferative Disorders

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ramya M Ramaswami, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

National Cancer Institute Referral Offic

CONTACT

(888) 624-1937; ncimo_referrals@mail.nih.gov

Ramya M Ramaswami, M.D.

CONTACT

(240) 506-1088; ramya.ramaswami@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 25, 2023
• Study Start: March 17, 2025
• Primary Completion (Estimated): January 1, 2033
• Study Completion (Estimated): January 1, 2034
• Last Updated: April 28, 2026

Record last verified: 2026-04-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested from other researchers after the completion of the primary endpoint.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)