What side effects are associated with this type of intervention?

The most common side effects of mTOR inhibitors, such as sirolimus, used in the treatment of Castleman Disease include hyperglycemia, hypercholesterolemia, abnormal liver function tests, and gastrointestinal issues like nausea and diarrhea. Other potential side effects are fatigue, rash, and increased susceptibility to infections. These side effects are generally mild but can lead to treatment discontinuation in some cases.

What prior FDA approvals exist?

The FDA has approved siltuximab, an anti-IL-6 monoclonal antibody, for the treatment of multicentric Castleman Disease (MCD). While sirolimus, an mTOR inhibitor, is being studied for its potential benefits in treating idiopathic multicentric Castleman Disease, there are no current FDA approvals for mTOR inhibitors specifically for this condition. Other treatments for Castleman Disease focus on targeting the underlying inflammatory pathways rather than mTOR inhibition.

What other types of research exist?

Promising novel alternatives to Sirolimus for Castleman Disease patients include monoclonal antibodies targeting interleukin-6 (IL-6) such as Siltuximab and Tocilizumab. These therapies have shown efficacy in reducing symptoms and controlling disease progression in clinical trials. Additionally, emerging therapies targeting other pathways involved in Castleman Disease, such as JAK inhibitors, may also offer new treatment options.

← Back to Search

mTOR inhibitor

Sirolimus for Castleman Disease

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.

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.

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.

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

Select...

I can take pills by mouth.

Select...

My condition shows active disease with at least two symptoms, including one measurable change.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I do not have HIV, HHV-8, or severe combined immunodeficiency syndrome.

Select...

I am not currently in, nor planning to join, another clinical trial for my condition.

Select...

I do not have any uncontrolled infections that could be confused with iMCD.

Select...

I have never been treated with sirolimus for my Castleman disease.

Select...

I have never had a liver or lung transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3, 6, 9, and 12 months ± 2 weeks

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

Cough

Pruritis

Arthralgia

Neutropenia

Abdominal Pain Upper

Dizziness

Pain in Extremity

Hepatic Enzyme Increased

Dyspnoea

Constipation

Sinusitis

Weight Decreased

Blood Creatinine Increased

Liver Function Test Abnormal

White Blood Cell Count Decreased

Muscle Spasms

Jaundice

Renal Failure

Decreased Appetite

Weight Increased

Upper Respiratory Tract Infection

Nasopharyngitis

Asthenia

Incision Site Pain

Depression

Anorexia

Night Sweats

Oropharyngeal Pain

Rhinorrhoea

Hyperlipidaemia

Thrombocytopenia

Pleural Effusion

Myalgia

Rash

Acne

Incisional Hernia

Sepsis

Pneumonia

Hypokalaemia

Renal Failure Acute

Hypoglycaemia

Urinary Retention

Clostridium Difficile Colitis

Cerebral Haemorrhage

Hepatic Artery Stenosis

Portal Vein Thrombosis

Gastrointestinal Tract Adenoma

Encephalopathy

Atrial Flutter

Transplant Rejection

Confusional State

Blood Alkaline Phosphatase Increased

Multi-Organ Failure

Chest Pain

Non-Small Cell Lung Cancer Metastatic

Benign Prostatic Hyperplasia

Ventricular Tachycardia

Febrile Neutropenia

Hepatic Failure

Hepatic Neoplasm Malignant

Gastritis

Epstein-Barr Virus Associated Lymphoproliferative Disorder

Crohn's Disease

Abdominal Hernia

Inappropriate Antidiuretic Hormone Secretion

Gastrointestinal Haemorrhage

Cardiac Failure Congestive

Blood Glucose Increased

Spinal Osteoarthritis

Hypercholesterolaemia

Convulsion

Peritonitis

Haemorrhage Intracranial

Deep Vein Thrombosis

Inguinal Hernia

Viral Infection

Acarodermatitis

Atrial Fibrillation

Malaise

Hepatic Cancer Metastatic

Adenocarcinoma

B-Cell Lymphoma

Desmoid Tumour

Pulmonary Embolism

Stomatitis

Influenza

Staphylococcal Infection

Umbilical Hernia

Hepatic Function Abnormal

Hyponatraemia

Bacteraemia

Cellulitis

Clostridial Infection

Diverticulitis

Escherichia Urinary Tract Infection

Lactobacillus Infection

Lobar Pneumonia

Pseudomonal Sepsis

Post Procedural Haemorrhage

Procedural Pain

Biliary Anastomosis Complication

Complications of Transplanted Kidney

Bile Duct Obstruction

Bile Duct Stenosis

Biliary Tract Disorder

Autoimmune Hepatitis

Cholestasis

Lung Disorder

Pulmonary Oedema

Sinus Congestion

Embolism Venous

Orthostatic Hypotension

Vasculitis

Hyperglycaemia

Graft Versus Host Disease

100%

80%

60%

40%

20%

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

0 / 8Eligibility criteria met

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.