KSHV Inflammatory Cytokine Syndrome (KICS) Clinical Trial
Official title:
Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS)
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.
| Status | Not yet recruiting |
| Enrollment | 65 |
| Est. completion date | January 1, 2034 |
| Est. primary completion date | January 1, 2033 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 120 Years |
| Eligibility | - 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/mm^3) - 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%) - Cardiac ejection fraction >=45% by echocardiogram at screening - Participants must have laboratory parameters as defined below: - Total bilirubin <=1.5 X upper limit of normal (ULN) - AST(SGOT)/ALT(SGPT) <=2.5 X ULN - PT/PTT/INR <=1.5 X ULN - Creatinine within normal institutional limits OR Creatinine clearance >=45 mL/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. - 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: - Symptomatic visceral KS (except for 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 moderate or strong inhibitors or inducers of CYP3A4 or strong inducers of CYP450. 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 >= 2 symptomatic non-dysrhythmia cardiac conditions or cardiac dysrhythmia within the last 6 months. - 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. - Participants with the following cardiac conditions at screening: - symptomatic congestive heart failure - unstable angina pectoris - uncontrolled cardiac dysrhythmias - QTc(Fredericia) prolongation >480 ms or other factors that increase the risk for QT prolongation (i.e., heart failure, or a history of long QT interval syndrome). - Left ventricular ejection fraction <= 50% by transthoracic echocardiogram (TTE) at screening. - 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.) |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Safety of pacritinib | Adverse events (AEs) will be reported by type and grade of toxicity | Prior to each cycle, at EOT, and safety visit. | |
| Secondary | Time to treatment failure and duration of benefit | The interval between initiating therapy and the earliest of clinical progression and and the time from to disease progression or death in patients who achieve CR, PR, or SD. | Prior to each cycle and at EOT and 1 year post treatment | |
| Secondary | Effect of pacritinib on concurrent diagnosis of Kaposi sarcoma (KS) | Fraction of participants who have a coexisting diagnosis of KS and who develop a response of any degree (PR; SD) | Prior to each cycle |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT01419561 -
Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS)
|
Phase 2 |