Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 22 January 2024
• Main ID: NCT03933904
• Date of registration: 29/04/2019
• Prospective Registration: Yes
• Primary sponsor: University of Pennsylvania
• Public title: Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease
• Scientific title: A Phase II, Single-arm Open-label Multi-center Study of Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease
• Date of first enrolment: September 25, 2019
• Target sample size: 24
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03933904
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: David C Fajgenbaum, MD, MBA, MS
• Affiliation: University of Pennsylvania

• Name: David C Fajgenbaum, MD, MBA, MS

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female, age 2-80

- Documented disease history consistent with the diagnostic criteria for iMCD

- Failed/refractory (patient did not achieve sufficient disease control with anti-IL-6
therapy, as determined by the site investigator), relapsed (return of symptoms while
on therapy), or inability to tolerate anti-IL-6 or anti-IL-6 receptor therapy

- Evidence of active disease, defined as at least two abnormalities in the criteria
comprising the CBR criteria, including at least one objective measurement (hemoglobin,
weight loss, or lymph node size)

- Ability to consume oral medication in the form of a tablet

- Ability to provide, or for a legally authorized representative to provide on their
behalf, informed consent prior to any study-specific activities

Exclusion Criteria:

- Subjects cannot be pregnant or nursing females

- Except for anti-IL6 blockade therapy (siltuximab or tocilizumab), the last dose of
which must be = 14 days prior to enrollment (unless subjects cannot or are unwilling
to undergo a 14 day washout period), subjects cannot have received any systemic
therapy(ies) intended to treat iMCD other than corticosteroids within 28 days of
enrollment

- Subjects cannot have previously received sirolimus monotherapy to treat iMCD

- Subjects cannot have any of the following: ECOG >3 (or Karnofsky/Lansky score = 60 in
children); Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 or
creatinine > 3.0 mg/dL; Absolute neutrophil count (ANC) < 1000 x 109/L ((< 500 x 109/L
in children); Hemoglobin = 6.5 g/dL (transfusion independent, defined as not receiving
a red blood cell transfusion for = 7 days prior); Aspartate aminotransferase (AST) or
alanine aminotransferase (ALT) laboratory values greater than three times the upper
limit of normal; Albumin < 2 g/dL (transfusion independent, defined as not receiving
intravenous albumin for = 7 days prior); Platelet count = 40 x 109/L (transfusion
independent, defined as not receiving platelet transfusion for = 7 days prior);
Pulmonary involvement or interstitial pneumonitis with dyspnea (adequate pulmonary
function is defined as pulse oximetry > 94% on room air if there is clinical
indication for determination (e.g. dyspnea at rest, history of interstitial
pneumonitis, etc.)); Fasting cholesterol > 300 mg/dL or fasting triglyceride > 400
mg/dL

- Subjects cannot have uncontrolled infection or infectious disease(s) that is/are
exclusionary for / mimickers of iMCD

- Subjects cannot have rheumatologic disease(s) that is/are exclusionary for / mimickers
of iMCD

- Subjects cannot have a prior malignancy except for: (1) adequately treated basal cell
or squamous cell skin cancer, (2) in situ cervical cancer, or (3) other cancer for
which the subject has not received treatment within one year prior to enrollment

- Subjects cannot have a documented history of human immunodeficiency virus (HIV) or
HHV-8 infection, or severe combined immunodeficiency syndrome

- Subjects cannot have a history of liver or lung transplantation

- Subjects cannot have ongoing or planned participation in another clinical trial
involving iMCD directed treatment or that involves immunomodulatory or anti-neoplastic
treatment

- Subjects cannot have prior sensitivity / allergy to any formulation of sirolimus, its
components or its analogues

- Subjects cannot have serious medical illness, or psychiatric illness or disorders that
could potentially interfere with the completion of treatment according to this
protocol or participation in the trial

- Subjects cannot have psychiatric disorders that compromises the ability to provide
informed consent

- Subjects cannot have any other condition or finding that in the opinion of the
investigator would make participation in this trial inappropriate



Age minimum: 2 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Castleman's Disease, Multicentric

Castleman Disease

Intervention(s)

Drug: Sirolimus

Primary Outcome(s)

Proportion of patients achieving a positive clinical benefit response (CBR) [Time Frame: 12 ± 1 months]

Secondary Outcome(s)

Disease activity, as measured by the CHAP scale [Time Frame: 3, 6, 9, and 12 months ± 2 weeks]

Proportion of patients that remain on study drug for the duration of the study [Time Frame: Up to 73 weeks]

Proportion of patients achieving a lymph node response, following the modified Cheson response criteria [Time Frame: 3, 6, 9, and 12 months ± 2 weeks]

Disease activity, as measured by the MCD-related Overall Symptom Score [Time Frame: 3, 6, 9, and 12 months ± 2 weeks]

Proportion of patients that indicate that they are currently receiving sirolimus at the end of the Follow Up Phase [Time Frame: Up to 73 weeks]

Proportion of patients achieving a positive clinical benefit response (CBR) [Time Frame: 3, 6, and 9 months ± 2 weeks]

Secondary ID(s)

832465

Source(s) of Monetary Support

Please refer to primary and secondary sponsors