NCT03933904

Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease

A Phase II, Single-arm Open-label Multi-center Study of Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: University of Pennsylvania · Academic / Other
• Sex: All
• Age: 2 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to understand the impact of sirolimus on idiopathic multicentric Castleman disease.

Detailed description

Human herpesvirus(HHV)-8-negative, idiopathic multicentric Castleman disease (iMCD) is a rare hematologic illness. Current therapeutic options are limited and provide benefit for only a subset of patients. Blockade of IL-6 signaling with siltuximab or tocilizumab abrogates symptoms and improves lymphadenopathy in a portion of patients. However, 66% of patients in the siltuximab Phase II clinical trial did not meet response criteria, and recent studies found that IL-6 is not significantly elevated in many iMCD patients. Recent research has suggested a key role for the phosphoinositide 3-kinase(PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway in iMCD pathogenesis and off-label administration of sirolimus, an mTOR inhibitor, has shown clinical activity. Based on these experiences, we plan to evaluate the efficacy of sirolimus as a therapy for iMCD patients who are either unable to tolerate anti-IL-6 blockade therapy (siltuximab or tocilizumab), or who fail, relapse, or are refractory to such treatment. This study is a Phase II open label study of daily administration of sirolimus in up to 24 evaluable male or female adults. Participants with iMCD who have failed previous therapy will take daily oral sirolimus for 12 months. Information that is collected as per standard of care will be used to review efficacy, in addition to samples collected specifically for research.

Conditions

• Castleman Disease
• Castleman's Disease, Multicentric

Interventions

Type	Name	Description
DRUG	Sirolimus	Sirolimus (also known as rapamycin) inhibits the mTOR protein kinase and is approved by the USA FDA for the prevention of allograft rejection in renal transplant patients ≥ 13 years of age and for the treatment of lymphangioleiomyomatosis.

Timeline

• Start date: 2019-09-25
• Primary completion: 2024-06-30
• Completion: 2026-06-30
• First posted: 2019-05-01
• Last updated: 2026-03-03
• Results posted: 2025-08-08

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study