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Trial record 2 of 39 for:    Castleman disease

Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03933904
Recruitment Status : Recruiting
First Posted : May 1, 2019
Last Update Posted : January 9, 2023
Information provided by (Responsible Party):
University of Pennsylvania

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

Condition or disease Intervention/treatment Phase
Castleman Disease Castleman's Disease, Multicentric Drug: Sirolimus Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single-arm Open-label Multi-center Study of Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease
Actual Study Start Date : September 25, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Arm Intervention/treatment
Experimental: Sirolimus
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.
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.
Other Names:
  • Rapamune
  • Rapamycin

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

Secondary Outcome Measures :
  1. Proportion of patients achieving a positive clinical benefit response (CBR) [ Time Frame: 3, 6, and 9 months ± 2 weeks ]
  2. Proportion of patients that remain on study drug for the duration of the study [ Time Frame: Up to 73 weeks ]
  3. 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 ]
  4. Disease activity, as measured by the CHAP scale [ Time Frame: 3, 6, 9, and 12 months ± 2 weeks ]
    The CHAP scale consists of C-reactive protein (CRP), hemoglobin, albumin, and Eastern Cooperative Oncology Group (ECOG) performance score, each with a subscale range of 0-4. Each criterion in the CHAP scoring system provides a graded measure for a patient's disease activity. The sum of the four scores provides an objective scale for measuring a patient's disease activity and monitoring how it changes over time (scale range 0-16). A higher score indicates greater disease activity.

  5. Disease activity, as measured by the MCD-related Overall Symptom Score [ Time Frame: 3, 6, 9, and 12 months ± 2 weeks ]
    MCD-related Overall Symptom Score is measured by 34 MCD-related outcome measures

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03933904

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Contact: David C Fajgenbaum, MD, MBA, MS 215-614-0935
Contact: Tracey Sikora 215-614-0199

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United States, Arkansas
University of Arkansas for Medical Sciences Recruiting
Little Rock, Arkansas, United States, 72205
Contact: Brooke Carter    501-214-2499 ext 25871   
Principal Investigator: Frits van Rhee, MD, PHD         
United States, California
University of California - San Diego Not yet recruiting
La Jolla, California, United States, 92093
Contact: Aaron Goodman         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David Teachey         
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David C Fajgenbaum, MD, MBA, MSc    215-614-0935   
Contact: Tracey Sikora    215-614-0199   
Principal Investigator: David C Fajgenbaum, MD, MBA, MSc         
Sponsors and Collaborators
University of Pennsylvania
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Principal Investigator: David C Fajgenbaum, MD, MBA, MS University of Pennsylvania
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: University of Pennsylvania Identifier: NCT03933904    
Other Study ID Numbers: 832465
First Posted: May 1, 2019    Key Record Dates
Last Update Posted: January 9, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no current plan to share IPD.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Pennsylvania:
Castleman's Disease
multicentric Castleman's disease
multicentric Castleman disease
idiopathic Castleman disease
idiopathic Castleman's disease
Castleman Disease
Additional relevant MeSH terms:
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Castleman Disease
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs