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mTOR inhibitor

Sirolimus for Castleman Disease

Philadelphia, PA
Phase 2
Waitlist Available
Led By David C Fajgenbaum, MD, MBA, MS
Research Sponsored by University of Pennsylvania
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Ability to consume oral medication in the form of a tablet
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)
Must not have
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 a documented history of human immunodeficiency virus (HIV) or HHV-8 infection, or severe combined immunodeficiency syndrome
Timeline
Screening 3 weeks
Treatment Varies
Follow Up 3, 6, 9, and 12 months ± 2 weeks
Awards & highlights
No Placebo-Only Group

Summary

This trial tests sirolimus, a medication that controls the immune system, on patients with iMCD who haven't responded to other treatments. Sirolimus blocks a pathway to reduce immune response and abnormal cell growth. Sirolimus has shown potential in treating various conditions.

See full description
Who is the study for?
This trial is for people aged 2-80 with idiopathic multicentric Castleman disease who haven't responded well to anti-IL-6 therapy or can't tolerate it. Participants must have active disease, be able to take oral medication, and not be pregnant or nursing. They shouldn't have had sirolimus before, any recent other systemic therapies except corticosteroids, severe infections mimicking iMCD, certain cancers within the last year, serious psychiatric disorders affecting consent ability, or very poor health as defined by specific medical criteria.Check my eligibility
What is being tested?
The study tests the effect of Sirolimus on patients with idiopathic multicentric Castleman disease who haven’t seen improvement with standard treatments. It aims to understand how this drug impacts their condition.See study design
What are the potential side effects?
Sirolimus may cause side effects like mouth sores, diarrhea, nausea; increased risk of infection; abnormal blood test results indicating liver or kidney issues; and potentially lung problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I can take pills by mouth.
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My condition shows active disease with at least two symptoms, including one measurable change.
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Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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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
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I do not have HIV, HHV-8, or severe combined immunodeficiency syndrome.
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I am not currently in, nor planning to join, another clinical trial for my condition.
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I do not have any uncontrolled infections that could be confused with iMCD.
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I have never been treated with sirolimus for my Castleman disease.
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I have never had a liver or lung transplant.
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Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~3, 6, 9, and 12 months ± 2 weeks
This trial's timeline: 3 weeks for screening, Varies for treatment, and 3, 6, 9, and 12 months ± 2 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Secondary study objectives
Disease activity, as measured by the CHAP scale
Disease activity, as measured by the MCD-related Overall Symptom Score

Side effects data

From 2008 Phase 4 trial • 293 Patients • NCT00118742
29%
Diarrhoea
18%
Abdominal Pain
16%
Nausea
16%
Headache
16%
Fatigue
16%
Hepatitis C
14%
Vomiting
14%
Pyrexia
14%
Leukopenia
12%
Oedema Peripheral
11%
Insomnia
10%
Anaemia
10%
Hyperkalaemia
10%
Tremor
10%
Back Pain
10%
Hypertension
9%
Cough
9%
Pruritis
9%
Arthralgia
8%
Neutropenia
8%
Abdominal Pain Upper
8%
Dizziness
8%
Pain in Extremity
8%
Hepatic Enzyme Increased
7%
Dyspnoea
7%
Constipation
7%
Sinusitis
7%
Weight Decreased
6%
Blood Creatinine Increased
6%
Liver Function Test Abnormal
6%
White Blood Cell Count Decreased
5%
Muscle Spasms
5%
Decreased Appetite
5%
Renal Failure
5%
Jaundice
5%
Weight Increased
5%
Upper Respiratory Tract Infection
5%
Nasopharyngitis
5%
Asthenia
5%
Incision Site Pain
5%
Depression
4%
Anorexia
4%
Night Sweats
4%
Oropharyngeal Pain
4%
Rhinorrhoea
3%
Hyperlipidaemia
3%
Thrombocytopenia
3%
Pleural Effusion
3%
Myalgia
3%
Rash
3%
Acne
3%
Incisional Hernia
2%
Hypokalaemia
2%
Sepsis
2%
Pneumonia
1%
Urinary Retention
1%
Hypoglycaemia
1%
Renal Failure Acute
1%
Cerebral Haemorrhage
1%
Cardiac Failure Congestive
1%
Hypercholesterolaemia
1%
Hepatic Artery Stenosis
1%
Portal Vein Thrombosis
1%
Encephalopathy
1%
Transplant Rejection
1%
Blood Alkaline Phosphatase Increased
1%
Multi-Organ Failure
1%
Chest Pain
1%
Crohn's Disease
1%
Non-Small Cell Lung Cancer Metastatic
1%
Atrial Flutter
1%
Benign Prostatic Hyperplasia
1%
Ventricular Tachycardia
1%
Febrile Neutropenia
1%
Hepatic Failure
1%
Gastritis
1%
Gastrointestinal Tract Adenoma
1%
Clostridium Difficile Colitis
1%
Epstein-Barr Virus Associated Lymphoproliferative Disorder
1%
Confusional State
1%
Hepatic Neoplasm Malignant
1%
Abdominal Hernia
1%
Inappropriate Antidiuretic Hormone Secretion
1%
Gastrointestinal Haemorrhage
1%
Blood Glucose Increased
1%
Spinal Osteoarthritis
1%
Convulsion
1%
Peritonitis
1%
Haemorrhage Intracranial
1%
Deep Vein Thrombosis
1%
Inguinal Hernia
1%
Viral Infection
1%
Acarodermatitis
1%
Atrial Fibrillation
1%
Malaise
1%
Hepatic Cancer Metastatic
1%
Adenocarcinoma
1%
B-Cell Lymphoma
1%
Desmoid Tumour
1%
Pulmonary Embolism
1%
Stomatitis
1%
Influenza
1%
Staphylococcal Infection
1%
Umbilical Hernia
1%
Hepatic Function Abnormal
1%
Hyponatraemia
1%
Bacteraemia
1%
Cellulitis
1%
Clostridial Infection
1%
Diverticulitis
1%
Escherichia Urinary Tract Infection
1%
Lactobacillus Infection
1%
Lobar Pneumonia
1%
Pseudomonal Sepsis
1%
Post Procedural Haemorrhage
1%
Procedural Pain
1%
Biliary Anastomosis Complication
1%
Complications of Transplanted Kidney
1%
Bile Duct Obstruction
1%
Bile Duct Stenosis
1%
Biliary Tract Disorder
1%
Autoimmune Hepatitis
1%
Cholestasis
1%
Lung Disorder
1%
Pulmonary Oedema
1%
Sinus Congestion
1%
Embolism Venous
1%
Orthostatic Hypotension
1%
Vasculitis
1%
Hyperglycaemia
1%
Graft Versus Host Disease
100%
80%
60%
40%
20%
0%
Study treatment Arm
CellCept + CNI (Tacrolimus or Cyclosporine)
CellCept + Sirolimus

Awards & Highlights

No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups
Experimental Treatment
Group I: SirolimusExperimental Treatment1 Intervention
Oral sirolimus: For adults, loading dose of 5 mg/m\^2, rounded to the nearest mg, on day 1. For adults, starting on day 2, oral sirolimus daily at 2.5 mg/m\^2/day (rounded to the nearest mg), target trough level 10-15 ng/mL by HPLC, for 12 months. For children, 2 mg/m\^2/day, target trough level 5-15 ng/mL by HPLC.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Sirolimus
2013
Completed Phase 4
~2750

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Castleman Disease treatments often target the dysregulated immune system and abnormal cell growth. Sirolimus, an mTOR inhibitor, works by blocking the mTOR pathway, which is crucial for cell proliferation and survival. This inhibition can reduce the overactive immune response and abnormal lymph node growth seen in Castleman Disease. Other treatments may include monoclonal antibodies like siltuximab, which target interleukin-6 (IL-6), a cytokine involved in inflammation and immune response. By understanding and targeting these pathways, treatments can help manage symptoms and improve outcomes for Castleman Disease patients.

Find a Location

Closest Location:Children's Hospital of Philadelphia· Philadelphia, PA

Who is running the clinical trial?

University of PennsylvaniaLead Sponsor
2,082 Previous Clinical Trials
42,726,688 Total Patients Enrolled
2 Trials studying Castleman Disease
1,130 Patients Enrolled for Castleman Disease
David C Fajgenbaum, MD, MBA, MSPrincipal InvestigatorUniversity of Pennsylvania

Media Library

Sirolimus (mTOR inhibitor) Clinical Trial Eligibility Overview. Trial Name: NCT03933904 — Phase 2
Castleman Disease Research Study Groups: Sirolimus
Castleman Disease Clinical Trial 2023: Sirolimus Highlights & Side Effects. Trial Name: NCT03933904 — Phase 2
Sirolimus (mTOR inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT03933904 — Phase 2
~4 spots leftby Dec 2025