Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS) : Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS)
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interleukin 6 receptor (IL-6R); this should also include signaling through gp130 mediated by KSHV vIL-6.In preliminary unpublished results, the Yarchoan lab has found that pacritinib is highly active against primary effusion lymphoma (PEL) cells in vitro.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 KSHV-MCD.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 CriteriaEligibility:-Pathologically confirmed MCD or evidence of KICSAge >=18At least one clinical symptom and at least one laboratory attributable to KSHV-MCD or KICSECOG performance status <= 3No life- or organ-threatening manifestations of MCD or KICSNo concurrent diagnosis of PELNo 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, with accrual ceiling set at 65 participants..
| Medienart: |
|
|---|
Klinische Studie| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
ClinicalTrials.gov - (2024) vom: 02. Apr. Zur Gesamtaufnahme - year:2024 |
|---|
| Sprache: |
Englisch |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
610 |
|---|
| Anmerkungen: |
Source: Link to the current ClinicalTrials.gov record., First posted: September 25, 2023, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024 |
|---|
| Study ID: |
NCT06052618 |
|---|---|
| Veröffentlichungen zur Studie: |
|
| fisyears: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
CTG000046450 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | CTG000046450 | ||
| 003 | DE-627 | ||
| 005 | 20240403010505.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240313s2024 xx |||||o 00| ||eng c | ||
| 035 | |a (DE-627)CTG000046450 | ||
| 035 | |a (UBBS_Klinische_Studien)NCT06052618 | ||
| 035 | |a (UBBS_Klinische_Studien)10001537 | ||
| 035 | |a (UBBS_Klinische_Studien)001537-C | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 245 | 1 | 0 | |a Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS) |b Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS) |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Source: Link to the current ClinicalTrials.gov record., First posted: September 25, 2023, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024 | ||
| 520 | |a 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 KSHV-MCD.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 CriteriaEligibility:-Pathologically confirmed MCD or evidence of KICSAge >=18At least one clinical symptom and at least one laboratory attributable to KSHV-MCD or KICSECOG performance status <= 3No life- or organ-threatening manifestations of MCD or KICSNo concurrent diagnosis of PELNo 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, with accrual ceiling set at 65 participants. | ||
| 650 | 2 | |a Sarcoma, Kaposi | |
| 650 | 2 | |a Sarcoma | |
| 650 | 2 | |a Castleman Disease | |
| 650 | 2 | |a Syndrome | |
| 650 | 4 | |a Study Type: Interventional | |
| 650 | 4 | |a Recruitment Status: Not yet recruiting | |
| 650 | 4 | |a Phase: Phase 2 | |
| 650 | 4 | |a 610 | |
| 773 | 0 | 8 | |i Enthalten in |t ClinicalTrials.gov |g (2024) vom: 02. Apr. |
| 773 | 1 | 8 | |g year:2024 |g day:02 |g month:04 |
| 856 | 4 | 0 | |u https://clinicaltrials.gov/show/NCT06052618 |z kostenfrei |3 Volltext |
| 912 | |a GBV_CTG | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 02 |c 04 | ||