Ignite Creation Date:
2025-12-24 @ 9:20 PM
Ignite Modification Date:
2026-01-02 @ 4:43 AM
Study NCT ID:
NCT03933904
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-08-08
First Post:
2019-04-29
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2025-06-29', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D005871', 'term': 'Castleman Disease'}, {'id': 'C537372', 'term': "Multi-centric Castleman's Disease"}, {'id': 'C537834', 'term': 'Macular dystrophy, corneal type 1'}], 'ancestors': [{'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D020123', 'term': 'Sirolimus'}], 'ancestors': [{'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'davidfa@pennmedicine.upenn.edu', 'phone': '215-614-0935', 'title': 'Dr. David Fajgenbaum', 'organization': 'Center for Cytokine Storm Treatment & Laboratory (CSTL), University of Pennsylvania'}, 'certainAgreement': {'restrictionType': 'LTE60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': "The study's single-arm, open-label design limited conclusions, as there was no control group and potential for bias. The small sample size, impacted by COVID-19 and off-label sirolimus use, reduced statistical power. A short follow-up (12 months plus 12 weeks) limited assessment of long-term efficacy and safety. Given iMCD's chronic nature, future studies should include larger cohorts, control arms, and extended follow-up to assess durability and safety."}}, 'adverseEventsModule': {'timeFrame': 'Adverse events were collected from baseline to study completion (up to 73 weeks).', 'description': 'Subjects were monitored for all previously reported AEs associated with sirolimus treatment, possible new AEs, and any Grade 2 or higher allergic reaction or hypersensitivity attributed to sirolimus, as judged by the site investigator. AEs were defined according to the NCI CTCAE version 5.0, November 2017. All AEs were recorded in the source document.', 'eventGroups': [{'id': 'EG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.', 'otherNumAtRisk': 7, 'deathsNumAtRisk': 7, 'otherNumAffected': 7, 'seriousNumAtRisk': 7, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Pruritus', 'notes': 'A disorder characterized by an intense itching sensation.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 3, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Bile duct stenosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Blood and lymphatic system disorders-Other, specify', 'notes': 'Neck lymph nodes enlarging', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Cough', 'notes': 'Productive cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Conjunctivitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Covid-19 Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Dysphagia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Dyspnea', 'notes': 'positive d-dimer finding', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Eye pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Hyperhidrosis', 'notes': 'Night sweats', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Itchy on palms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Lung infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Muscle cramp', 'notes': 'Cramping of calves and thighs at night', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Neck pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Neuropathy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Peripheral sensory neuropathy', 'notes': 'Worsening feet neuropathy; Intermittent numbness and pain in one arm', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Pleural effusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Rash acneiform', 'notes': 'hands and head', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Shortness of breath', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Skin hyperpigmentation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Sore throat', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Tremors', 'notes': 'Worsening tremors', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Urinary Tract Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Respiratory, thoracic and mediastinal disorders - Other', 'notes': 'Subjective report of being unable to breathe as deeply. Said he has been using albuterol, PRN.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Skin and subcutaneous tissue disorders - Other, specify (ankle)', 'notes': 'Ankle rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Skin and subcutaneous tissue disorders - Other, specify (groin)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Skin and subcutaneous tissue disorders - Other, specify (torso)', 'notes': 'Rash on torso', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Skin and subcutaneous tissue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Lump on knee', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Gastrointestinal disorders - Other (tongue ulcer)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Mucositis oral (mouth sores)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Generalized muscle weakness (worsening)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Fever', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Fatigue', 'notes': "Stated worst fatigue they've had thus far.", 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Dry cough (worsening)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Chills', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Ascites (worsening)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Edema limb (leg swelling)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Lip pain', 'notes': 'Lips burn', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Hypertriglyceridemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Swelling of hands and feet (Edema limbs)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Vascular disorders - Other', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Worsening of night sweats', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Worsening of rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Pain (whole body)', 'notes': 'Intermittent lower leg pain; feeling "achey"', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}], 'seriousEvents': [{'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}, {'term': 'Sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 7, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'NCI CTCAE version 5'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': '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.\n\nSirolimus: 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.'}], 'classes': [{'categories': [{'title': 'Achieved CBR', 'measurements': [{'value': '2', 'groupId': 'OG000'}]}, {'title': 'Did Not Achieve CBR', 'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '12 ± 1 months', 'description': '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.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 3', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Month 3', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Month 6', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 9', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Month 9', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Patients That Remain on Study Drug for the Duration of the Study', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Up to 73 weeks', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percentage of Patients That Indicate That They Are Currently Receiving Sirolimus at the End of the Follow Up Phase', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Up to 73 weeks', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Disease Activity, as Measured by the CHAP Scale', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'spread': '0.433', 'groupId': 'OG000'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '12 months ± 2 weeks', 'description': "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.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Disease Activity, as Measured by the MCD-related Overall Symptom Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'categories': [{'title': 'Achieved a Symptomatic Response', 'measurements': [{'value': '1', 'groupId': 'OG000'}]}, {'title': 'Achieved a Durable Symptomatic Response', 'measurements': [{'value': '1', 'groupId': 'OG000'}]}, {'title': 'No Response', 'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Month 12', 'description': '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 symptomatic response was defined as a ≥50% decrease in the 34-point symptom score, a durable symptomatic response is a ≥50% decrease in the 34-point symptom score from baseline that was maintained for a minimum of 18 weeks.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Proportion of Patients Achieving a Lymph Node Response, Following the Modified Cheson Response Criteria', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'classes': [{'title': 'Achieved Complete Response', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Progressive Disease', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Stable Disease', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Month 12', 'description': '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:\n\nComplete 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.\n\nPartial Response: ≥50% decrease in sum of the products of the greatest diameters (SPD) of index lesion(s), and no new sites of lymphadenopathy \\>1.5 cm in longest dimension.\n\nStable Disease: Failure to achieve a CR or PR (see above) without evidence of progressive disease.\n\nProgressive Disease: ≥50% increase from nadir in the SPD of any index lesion, or appearance of any new sites of lymphadenopathy that measure \\>1.5 cm in longest dimension during or at the end of therapy.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Sirolimus', 'description': 'For adults, the treatment began with a loading dose of 5 mg/m² on Day 1, designed to quickly achieve therapeutic levels of sirolimus. This loading dose was rounded to the nearest milligram and could be adjusted at the discretion of the prescribing physician based on individual tolerability and clinical judgment.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}]}]}], 'recruitmentDetails': 'Recruitment started 9/25/2019 and continued until 6/30/2024. Potential participants were informed about the study through various channels, including communication and fliers from licensed site investigators during routine clinical visits. Individuals who previously consented to be contacted for future research were reached by email or phone. Additional outreach was conducted through tools like Epic as well as through the Castleman Disease Collaborative Network (CDCN).', 'preAssignmentDetails': 'Before assignment, participants underwent several steps to confirm eligibility. This included a washout period from any systemic therapies used to treat iMCD, as well as various laboratory tests to ensure they were healthy enough to participate and did not have any uncontrolled infections or conditions that could mimic iMCD.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Sirolimus', 'description': 'Oral sirolimus: Loading dose of 5 mg/m\\^2, rounded to the nearest mg, on day 1. 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.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '57', 'groupId': 'BG000', 'lowerLimit': '34', 'upperLimit': '71'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '7', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Histopathological Subtype', 'classes': [{'categories': [{'title': 'Hypervascular/Hyaline Vascular', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Mixed', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Plasmacytic', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Indeterminate', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Clinical Subtype', 'classes': [{'categories': [{'title': 'Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis, and Organomegaly (TAFRO) Subtype', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Idiopathic Plasmacytic Lymphadenopathy (IPL) Subtype', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Not Otherwise Specified (NOS) Subtype', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': '7 patients enrolled into the study with 4 evaluable patients who remained in study for more than 6 weeks.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2024-03-20', 'size': 1595227, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_002.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2025-07-01T16:33', 'hasProtocol': True}, {'date': '2024-04-11', 'size': 427120, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_003.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-07-01T16:33', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 7}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2019-09-25', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2026-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-22', 'studyFirstSubmitDate': '2019-04-29', 'resultsFirstSubmitDate': '2025-06-13', 'studyFirstSubmitQcDate': '2019-04-29', 'lastUpdatePostDateStruct': {'date': '2025-08-08', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-07-22', 'studyFirstPostDateStruct': {'date': '2019-05-01', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-08-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-06-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR)', 'timeFrame': '12 ± 1 months', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 3', 'timeFrame': 'Month 3'}, {'measure': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 6', 'timeFrame': 'Month 6'}, {'measure': 'Percentage of Patients Achieving a Positive Clinical Benefit Response (CBR) Month 9', 'timeFrame': 'Month 9'}, {'measure': 'Percentage of Patients That Remain on Study Drug for the Duration of the Study', 'timeFrame': 'Up to 73 weeks'}, {'measure': 'Percentage of Patients That Indicate That They Are Currently Receiving Sirolimus at the End of the Follow Up Phase', 'timeFrame': 'Up to 73 weeks'}, {'measure': 'Disease Activity, as Measured by the CHAP Scale', 'timeFrame': '12 months ± 2 weeks', 'description': "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."}, {'measure': 'Disease Activity, as Measured by the MCD-related Overall Symptom Score', 'timeFrame': 'Month 12', 'description': '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 symptomatic response was defined as a ≥50% decrease in the 34-point symptom score, a durable symptomatic response is a ≥50% decrease in the 34-point symptom score from baseline that was maintained for a minimum of 18 weeks.'}, {'measure': 'Proportion of Patients Achieving a Lymph Node Response, Following the Modified Cheson Response Criteria', 'timeFrame': 'Month 12', 'description': '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:\n\nComplete 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.\n\nPartial Response: ≥50% decrease in sum of the products of the greatest diameters (SPD) of index lesion(s), and no new sites of lymphadenopathy \\>1.5 cm in longest dimension.\n\nStable Disease: Failure to achieve a CR or PR (see above) without evidence of progressive disease.\n\nProgressive Disease: ≥50% increase from nadir in the SPD of any index lesion, or appearance of any new sites of lymphadenopathy that measure \\>1.5 cm in longest dimension during or at the end of therapy.'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Castleman', 'iMCD', "Castleman's Disease", "multicentric Castleman's disease", 'multicentric Castleman disease', 'idiopathic Castleman disease', "idiopathic Castleman's disease", 'CD', 'MCD', 'Castleman Disease'], 'conditions': ['Castleman Disease', "Castleman's Disease, Multicentric"]}, 'referencesModule': {'references': [{'pmid': '33284946', 'type': 'DERIVED', 'citation': 'van Rhee F, Oksenhendler E, Srkalovic G, Voorhees P, Lim M, Dispenzieri A, Ide M, Parente S, Schey S, Streetly M, Wong R, Wu D, Maillard I, Brandstadter J, Munshi N, Bowne W, Elenitoba-Johnson KS, Fossa A, Lechowicz MJ, Chandrakasan S, Pierson SK, Greenway A, Nasta S, Yoshizaki K, Kurzrock R, Uldrick TS, Casper C, Chadburn A, Fajgenbaum DC. International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease. Blood Adv. 2020 Dec 8;4(23):6039-6050. doi: 10.1182/bloodadvances.2020003334.'}, {'pmid': '32206779', 'type': 'DERIVED', 'citation': 'Arenas DJ, Floess K, Kobrin D, Pai RL, Srkalovic MB, Tamakloe MA, Rasheed R, Ziglar J, Khor J, Parente SAT, Pierson SK, Martinez D, Wertheim GB, Kambayashi T, Baur J, Teachey DT, Fajgenbaum DC. Increased mTOR activation in idiopathic multicentric Castleman disease. Blood. 2020 May 7;135(19):1673-1684. doi: 10.1182/blood.2019002792.'}, {'pmid': '31408438', 'type': 'DERIVED', 'citation': 'Fajgenbaum DC, Langan RA, Japp AS, Partridge HL, Pierson SK, Singh A, Arenas DJ, Ruth JR, Nabel CS, Stone K, Okumura M, Schwarer A, Jose FF, Hamerschlak N, Wertheim GB, Jordan MB, Cohen AD, Krymskaya V, Rubenstein A, Betts MR, Kambayashi T, van Rhee F, Uldrick TS. Identifying and targeting pathogenic PI3K/AKT/mTOR signaling in IL-6-blockade-refractory idiopathic multicentric Castleman disease. J Clin Invest. 2019 Aug 13;129(10):4451-4463. doi: 10.1172/JCI126091.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to understand the impact of sirolimus on idiopathic multicentric Castleman disease.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '2 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female, age 2-80\n* Documented disease history consistent with the diagnostic criteria for iMCD\n* 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\n* 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)\n* Ability to consume oral medication in the form of a tablet\n* Ability to provide, or for a legally authorized representative to provide on their behalf, informed consent prior to any study-specific activities\n\nExclusion Criteria:\n\n* Subjects cannot be pregnant or nursing females\n* 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\n* Subjects cannot have previously received sirolimus monotherapy to treat iMCD\n* 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\n* Subjects cannot have uncontrolled infection or infectious disease(s) that is/are exclusionary for / mimickers of iMCD\n* Subjects cannot have rheumatologic disease(s) that is/are exclusionary for / mimickers of iMCD\n* 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\n* Subjects cannot have a documented history of human immunodeficiency virus (HIV) or HHV-8 infection, or severe combined immunodeficiency syndrome\n* Subjects cannot have a history of liver or lung transplantation\n* Subjects cannot have ongoing or planned participation in another clinical trial involving iMCD directed treatment or that involves immunomodulatory or anti-neoplastic treatment\n* Subjects cannot have prior sensitivity / allergy to any formulation of sirolimus, its components or its analogues\n* 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\n* Subjects cannot have psychiatric disorders that compromises the ability to provide informed consent\n* Subjects cannot have any other condition or finding that in the opinion of the investigator would make participation in this trial inappropriate'}, 'identificationModule': {'nctId': 'NCT03933904', 'briefTitle': 'Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease', 'organization': {'class': 'OTHER', 'fullName': 'University of Pennsylvania'}, 'officialTitle': 'A Phase II, Single-arm Open-label Multi-center Study of Sirolimus in Previously Treated Idiopathic Multicentric Castleman Disease', 'orgStudyIdInfo': {'id': '832465'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sirolimus', 'description': '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.', 'interventionNames': ['Drug: Sirolimus']}], 'interventions': [{'name': 'Sirolimus', 'type': 'DRUG', 'otherNames': ['Rapamune', 'Rapamycin'], 'description': '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.', 'armGroupLabels': ['Sirolimus']}]}, 'contactsLocationsModule': {'locations': [{'zip': '72205', 'city': 'Little Rock', 'state': 'Arkansas', 'country': 'United States', 'facility': 'University of Arkansas for Medical Sciences', 'geoPoint': {'lat': 34.74648, 'lon': -92.28959}}, {'zip': '92093', 'city': 'La Jolla', 'state': 'California', 'country': 'United States', 'facility': 'University of California - San Diego', 'geoPoint': {'lat': 32.84727, 'lon': -117.2742}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': "Children's Hospital of Philadelphia", 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pennsylvania', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}], 'overallOfficials': [{'name': 'David C Fajgenbaum, MD, MBA, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Pennsylvania'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'There is no current plan to share IPD.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Pennsylvania', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}