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NCT03933904

Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease

Active, enrolled Phase 2 Results posted Last updated 3 March 2026
What this trial tests

Phase 2 trial testing Sirolimus in Castleman Disease in 7 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
25 September 2019
Primary endpoint
30 June 2024
30 June 2026

Quick facts

Lead sponsorUniversity of Pennsylvania
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment7
Start date25 September 2019
Primary completion30 June 2024
Estimated completion30 June 2026
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Pennsylvania

Who can join

Adults 2 to 80, any sex, with Castleman Disease or Castleman's Disease, Multicentric. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Primary · 12 ± 1 months

Clinical Benefit Response (CBR): The CBR was defined by improvements in clinical symptoms such as fatigue, anorexia, fever, and night sweats.6 Laboratory markers such as hemoglobin levels and weight change were also included in the CBR criteria (Table 1). A CBR was considered positive if there was at least a 25% reduction in the size of the largest lymph node (measured by modified Cheson criteria), a significant improvement in at least one laboratory marker (e.g., hemoglobin), and improvement in at least one clinical symptom without worsening of others.

GroupValue95% CI
Sirolimus2
Sirolimus2
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 3 Secondary · Month 3
GroupValue95% CI
Sirolimus1
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 6 Secondary · Month 6
GroupValue95% CI
Sirolimus2
Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 9 Secondary · Month 9
GroupValue95% CI
Sirolimus2
Percentage of Patients That Remain on Study Drug for the Duration of the Study Secondary · Up to 73 weeks
GroupValue95% CI
Sirolimus4
Percentage of Patients That Indicate That They Are Currently Receiving Sirolimus at the End of the Follow Up Phase Secondary · Up to 73 weeks
GroupValue95% CI
Sirolimus1
Disease Activity, as Measured by the CHAP Scale Secondary · 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.

GroupValue95% CI
Sirolimus3± 0.433
Disease Activity, as Measured by the MCD-related Overall Symptom Score Secondary · Month 12

MCD-related Overall Symptom Score is measured by 34 MCD-related outcome measures. These scores addressed fatigue, weight change, night sweats, etc. The scores were evaluated and graded (as per CTCAE version 4.0, May, 2009), which was used to assess the efficacy of the study intervention. Each symptom score was measured on a numeric scale, ranging from 1 (no symptom) to 5 (very severe or disabling). Scores were combined to create a combined score per patient at each time point. Patients were then assessed as having no response, a symptomatic response, or a durable symptomatic response. A sympto

GroupValue95% CI
Sirolimus1
Sirolimus1
Sirolimus2
Proportion of Patients Achieving a Lymph Node Response, Following the Modified Cheson Response Criteria Secondary · Month 12

Radiological response was assessed using the modified Cheson criteria, which quantify changes in lymph node size. A lymph node response was defined as a 25% reduction in bi-dimensional measurements of the largest lymph node compared to baseline. Patients were then assessed according to the following responses: Complete Response: All index lesion(s) must have regressed to normal size (≤1.0 cm in their greatest transverse diameter. No new sites of lymphadenopathy \>1.5 cm in longest dimension. Partial Response: ≥50% decrease in sum of the products of the greatest diameters (SPD) of index lesio

Achieved Complete Response
GroupValue95% CI
Sirolimus1
Progressive Disease
GroupValue95% CI
Sirolimus2
Stable Disease
GroupValue95% CI
Sirolimus1

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from baseline to study completion (up to 73 weeks).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Sirolimus
Serious: 1/7 (14%)
Deaths: 0/7

Serious adverse events (2 terms)

ReactionSystemSirolimus
PneumoniaInfections and infestations
SepsisInfections and infestations
Other adverse events (51 terms — click to expand)

ReactionSystemSirolimus
FatigueGeneral disorders
HeadacheNervous system disorders
Pain (whole body)Musculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
HyperhidrosisSkin and subcutaneous tissue disorders
Shortness of breathRespiratory, thoracic and mediastinal disorders
Sore throatRespiratory, thoracic and mediastinal disorders
TremorsNervous system disorders
Mucositis oral (mouth sores)Gastrointestinal disorders
Ascites (worsening)Gastrointestinal disorders
Bile duct stenosisHepatobiliary disorders
Blood and lymphatic system disorders-Other, specifyBlood and lymphatic system disorders
ConjunctivitisEye disorders
Covid-19 InfectionInfections and infestations
DysphagiaGastrointestinal disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Eye painEye disorders
Itchy on palmsSkin and subcutaneous tissue disorders
Lung infectionInfections and infestations
Muscle crampMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Neck painMusculoskeletal and connective tissue disorders
NeuropathyNervous system disorders
Peripheral sensory neuropathyNervous system disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Rash acneiformSkin and subcutaneous tissue disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders
Urinary Tract InfectionInfections and infestations
Respiratory, thoracic and mediastinal disorders - OtherRespiratory, thoracic and mediastinal disorders
Skin and subcutaneous tissue disorders - Other, specify (ankle)Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify (groin)Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify (torso)Skin and subcutaneous tissue disorders
Skin and subcutaneous tissueSkin and subcutaneous tissue disorders
Lump on kneeMusculoskeletal and connective tissue disorders
Gastrointestinal disorders - Other (tongue ulcer)Gastrointestinal disorders
Generalized muscle weakness (worsening)Nervous system disorders
FeverGeneral disorders

Most-reported serious reactions: Pneumonia, Sepsis.

Data from ClinicalTrials.gov NCT03933904 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cytokine Storm.
    Fajgenbaum DC, June CH. · · 2020 · cited 2313× · PMID 33264547 · DOI 10.1056/nejmra2026131
  2. Overview of Castleman disease.
    Dispenzieri A, Fajgenbaum DC. · · 2020 · cited 327× · PMID 32106302 · DOI 10.1182/blood.2019000931
  3. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease.
    van Rhee F, Oksenhendler E, Srkalovic G, Voorhees P, et al · · 2020 · cited 151× · PMID 33284946 · DOI 10.1182/bloodadvances.2020003334
  4. Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes.
    England JT, Abdulla A, Biggs CM, Lee AYY, et al · · 2021 · cited 124× · PMID 32425294 · DOI 10.1016/j.blre.2020.100707
  5. Identifying and targeting pathogenic PI3K/AKT/mTOR signaling in IL-6-blockade-refractory idiopathic multicentric Castleman disease.
    Fajgenbaum DC, Langan RA, Japp AS, Partridge HL, et al · · 2019 · cited 110× · PMID 31408438 · DOI 10.1172/jci126091
  6. Increased mTOR activation in idiopathic multicentric Castleman disease.
    Arenas DJ, Floess K, Kobrin D, Pai RL, et al · · 2020 · cited 73× · PMID 32206779 · DOI 10.1182/blood.2019002792
  7. Type I IFN response associated with mTOR activation in the TAFRO subtype of idiopathic multicentric Castleman disease.
    Pai RL, Japp AS, Gonzalez M, Rasheed RF, et al · · 2020 · cited 49× · PMID 32376796 · DOI 10.1172/jci.insight.135031
  8. The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside.
    Feng Y, Chen X, Cassady K, Zou Z, et al · · 2020 · cited 38× · PMID 33489922 · DOI 10.3389/fonc.2020.611690

Verify or expand the search:

Other trials of Sirolimus

Trials testing the same drug.

Other recruiting trials for Castleman Disease

Currently open trials in the same condition.

Other University of Pennsylvania trials

Trials by the same sponsor.

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