Ignite Creation Date:
2024-05-06 @ 7:34 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06052618
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2023-09-22
Brief Title:
Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus KSHV-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome KICS
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus KSHV-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome KICS
Status:
RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 andor 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
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 andor 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
Detailed Description:
Background
Pacritinib is a JAK2tyrosine 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-MCDKICS 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 to be enrolled is 54
Pacritinib is a JAK2tyrosine 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-MCDKICS 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 to be enrolled is 54
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001537-C | None | None | None |