Ignite Creation Date:
2025-12-24 @ 9:10 PM
Ignite Modification Date:
2026-01-02 @ 4:14 AM
Study NCT ID:
NCT04470804
Status:
COMPLETED
Last Update Posted:
2023-02-28
First Post:
2020-07-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012010', 'term': 'Red-Cell Aplasia, Pure'}], 'ancestors': [{'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D016572', 'term': 'Cyclosporine'}], 'ancestors': [{'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D003524', 'term': 'Cyclosporins'}, {'id': 'D010456', 'term': 'Peptides, Cyclic'}, {'id': 'D047028', 'term': 'Macrocyclic Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 56}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2020-07-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-02', 'completionDateStruct': {'date': '2022-07-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-02-26', 'studyFirstSubmitDate': '2020-07-09', 'studyFirstSubmitQcDate': '2020-07-09', 'lastUpdatePostDateStruct': {'date': '2023-02-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-07-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2022-07-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Overall response', 'timeFrame': '1 year', 'description': 'complete response plus partial response'}, {'measure': 'Complete response', 'timeFrame': '1 year', 'description': 'Hemoglobin \\>120 g/L in males or Hemoglobin \\>110 g/L in females, and lasting for at least 2 months'}], 'primaryOutcomes': [{'measure': 'Hemoglobin level', 'timeFrame': '6 months', 'description': 'Hemoglobin level in g/L'}], 'secondaryOutcomes': [{'measure': 'Hemoglobin level', 'timeFrame': '2 years', 'description': 'Hemoglobin level in g/L'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['sirolimus', 'newly diagnosed pure red cell aplasia', 'prospective study'], 'conditions': ['Pure Red Cell Aplasia, Acquired']}, 'referencesModule': {'references': [{'pmid': '26504182', 'type': 'RESULT', 'citation': 'Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, Manno CS, Casper J, Grupp SA, Teachey DT. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016 Jan 7;127(1):17-28. doi: 10.1182/blood-2015-07-657981. Epub 2015 Oct 26.'}, {'pmid': '24363761', 'type': 'RESULT', 'citation': 'Li J, Wang Z, Dai L, Cao L, Su J, Zhu M, Yu Z, Bai X, Ruan C. Effects of rapamycin combined with low dose prednisone in patients with chronic immune thrombocytopenia. Clin Dev Immunol. 2013;2013:548085. doi: 10.1155/2013/548085. Epub 2013 Dec 2.'}, {'pmid': '27881371', 'type': 'RESULT', 'citation': 'Means RT Jr. Pure red cell aplasia. Blood. 2016 Nov 24;128(21):2504-2509. doi: 10.1182/blood-2016-05-717140.'}, {'pmid': '19208097', 'type': 'RESULT', 'citation': 'Teachey DT, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J, Manno C, Rappaport E, Schwabe D, Sheen C, Sullivan KE, Zhuang H, Wechsler DS, Grupp SA. Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol. 2009 Apr;145(1):101-6. doi: 10.1111/j.1365-2141.2009.07595.x. Epub 2009 Feb 4.'}, {'pmid': '29982851', 'type': 'RESULT', 'citation': 'Long Z, Yu F, Du Y, Li H, Chen M, Zhuang J, Han B. Successful treatment of refractory/relapsed acquired pure red cell aplasia with sirolimus. Ann Hematol. 2018 Nov;97(11):2047-2054. doi: 10.1007/s00277-018-3431-5. Epub 2018 Jul 7.'}, {'pmid': '32030447', 'type': 'RESULT', 'citation': 'Chen Z, Liu X, Chen M, Yang C, Han B. Successful sirolimus treatment of patients with pure red cell aplasia complicated with renal insufficiency. Ann Hematol. 2020 Apr;99(4):737-741. doi: 10.1007/s00277-020-03946-2. Epub 2020 Feb 6.'}, {'pmid': '37160872', 'type': 'DERIVED', 'citation': 'Yang Y, Tang Z, Huang Y, Hu Q, Wang S, Ji J, Du Y, Yang C, Chen M, Hu S, Han B. Sirolimus versus cyclosporine A in patients with primary acquired pure red cell aplasia: a prospective cohort study. Blood Cancer J. 2023 May 10;13(1):74. doi: 10.1038/s41408-023-00845-3. No abstract available.'}]}, 'descriptionModule': {'briefSummary': 'Pure red cell aplasia (PRCA) is a kind of anemia characterized by severe reticulocytopenia and obvious bone marrow erythroblastic cells decreased. Cyclosporine A and /or steroids are the first line therapy but some patients were refractory or intolerance to the treatment. The effects of the second line therapy are also not satisfactory and sometimes not available. The investigators aim to explore the efficacy and side-effect of sirolimus for newly diagnosed primary acquired PRCA.', 'detailedDescription': 'Pure red cell aplasia (PRCA) is a rare normocytic normochromic anemia with reticulocytopenia, characterized by a reduction of erythroid precursors from the bone marrow, could be divided into congenital and acquired PRCA according to pathogenesis. Congenital PRCA, also known as Diamond-Blackfan syndrome, has been associated with pathogenic variant in GATA1 and TSR2 and gene encode ribosomal proteins. Acquired PRCA can be a primary disease which is usually mediated by immunology, or secondary to other diseases, such as lymphoproliferative diseases, autoimmune diseases, thymoma, infection, or drugs. The first line therapy of acquired PRCA is Cyclosporine A (CsA) and steroids, the second line therapy are anti-CD20, anti-human thymocyte immunoglobulin, immunosuppressive drugs like cyclophosphamide, bone marrow transplantation. Unfortunately, some patients did not response or tolerate the above treatments.\n\nSirolimus (rapamycin) is an agent produced by the bacterium Streptomyces hygroscopicus, inhibits the mammalian target of rapamycin (mTOR). mTOR is a serine/threonine kinase that regulates cell growth, proliferation, metabolism and survival in eukaryotic cells, and is identified as two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits mTORC1, has been approved for prevent organ transplant rejection, especially in renal transplantation. Sirolimus also promises to treat autoimmune, degenerative and hyperproliferative disorders. Recently, sirolimus has been reported to be effective and well tolerated for many immune-mediated cytopenias, such as autoimmune lymphoproliferative syndrome, immune thrombocytopenia, EVANS syndrome, etc. Some case reports and our previous retrospective study showed that sirolimus was effective for refractory/relapse PRCA with good tolerance. However, due to the rare occurrence of PRCA and good response rate to CsA, there are very few studies of sirolimus on newly diagnosed PRCA so far.\n\nIn this study, It is anticipated to evaluate the efficacy and safety of sirolimus versus CsA in patients with newly diagnosed PRCA . The side-effects will be documented and plasma concentration of sirolimus will be monitored. Furthermore, an interim analysis will be performed to assess the treatment efficacy and safety of sirolimus versus CsA in primary PRCA patients when a total of 56 eligible participants finished the designed treatment.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '88 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. age \\>18 years old.\n2. hemoglobin (Hb) \\<90 g/L before treatment.\n3. no history of immunosuppression therapy prior to sirolimus or CsA treatment.\n4. adequate hepatic functions with alanine transaminase (ALT)/aspartate. transaminase (AST) levels within 3 times of the normal upper limit and total bilirubin levels within 2 times of the normal upper limit.\n5. documented patient consent.\n\nExclusion Criteria:\n\n1. diagnosis of secondary aPRCA.\n2. history of treatment with immunosuppression therapy before enrollment.\n3. history of leukemia, stem cell transplantation, or treatment-related myelodysplastic syndromes (MDS).\n4. creatinine/transaminase ≥ 3 normal upper limit.\n5. complicated with active or uncontrolled infections or uncontrolled cardiovascular disease.\n6. presence of other diseases that may cause anemia.\n7. presence of malignancies.\n8. pregnant and lactating women.'}, 'identificationModule': {'nctId': 'NCT04470804', 'acronym': 'PRCA', 'briefTitle': 'Sirolimus Treatment for Newly Diagnosed Primary Acquired PRCA', 'organization': {'class': 'OTHER', 'fullName': 'Peking Union Medical College Hospital'}, 'officialTitle': 'Sirolimus Treatment for Newly Diagnosed Primary Acquired Pure Red Cell Aplasia: a Single Center Prospective Study', 'orgStudyIdInfo': {'id': 'PRCA-2'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sirolimus on newly diagnosed primary acquired PRCA', 'description': 'A prospective research of the sirolimus efficiency on newly diagnosed primary acquired PRCA patients. Sirolimus dosage: 2mg QD with plasma concentration 4-15ng/mL. Medication time should last at least 6 months', 'interventionNames': ['Drug: Sirolimus']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Cyclosporine A on newly diagnosed primary acquired PRCA', 'description': 'Cyclosporine A (CsA) efficiency on newly diagnosed primary acquired PRCA patients. CsA dosage: 4mg/kg QD. Medication time should last at least 6 months', 'interventionNames': ['Drug: Cyclosporine A']}], 'interventions': [{'name': 'Sirolimus', 'type': 'DRUG', 'otherNames': ['Sirolimus Tablets'], 'description': 'Sirolimus treats in experimental group', 'armGroupLabels': ['Sirolimus on newly diagnosed primary acquired PRCA']}, {'name': 'Cyclosporine A', 'type': 'DRUG', 'otherNames': ['Cyclosporine A Tablets'], 'description': 'Cyclosporine A uses for active comparator group.', 'armGroupLabels': ['Cyclosporine A on newly diagnosed primary acquired PRCA']}]}, 'contactsLocationsModule': {'locations': [{'zip': '100730', 'city': 'Beijing', 'country': 'China', 'facility': 'Peking Union Medical College Hospital', 'geoPoint': {'lat': 39.9075, 'lon': 116.39723}}], 'overallOfficials': [{'name': 'Bing Han, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Peking Union Medical College Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Bing Han', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Bing Han', 'investigatorAffiliation': 'Peking Union Medical College Hospital'}}}}