Ignite Creation Date:
2025-12-25 @ 2:03 AM
Ignite Modification Date:
2026-01-07 @ 2:44 PM
Study NCT ID:
NCT02177760
Status:
WITHDRAWN
Last Update Posted:
2015-12-03
First Post:
2014-06-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Sirolimus Prophylaxis for aGVHD in TME SCID
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D016511', 'term': 'Severe Combined Immunodeficiency'}], 'ancestors': [{'id': 'D000081207', 'term': 'Primary Immunodeficiency Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}, {'id': 'D049914', 'term': 'DNA Repair-Deficiency Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'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'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'whyStopped': 'Preliminary data suggested a better approach available', 'overallStatus': 'WITHDRAWN', 'startDateStruct': {'date': '2014-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-12', 'completionDateStruct': {'date': '2015-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-12-01', 'studyFirstSubmitDate': '2014-06-19', 'studyFirstSubmitQcDate': '2014-06-27', 'lastUpdatePostDateStruct': {'date': '2015-12-03', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2014-06-30', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of aGVHD', 'timeFrame': '105 days', 'description': 'Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by UCSF SOP CL 221.06 by Day +100.'}], 'secondaryOutcomes': [{'measure': 'T-regulatory cell enumeration', 'timeFrame': '105 days', 'description': 'T-regulatory cell enumeration studies by blood draw prior to prophylaxis and at day +30, day+60, day+100.'}, {'measure': 'Sirolimus therapeutic drug monitoring', 'timeFrame': '105 days', 'description': 'Sirolimus therapeutic drug monitoring will be done via blood draws(after initial 4th dose; thereafter every 4th dose with adjustment; once stable it will be measured weekly). We will determine the average dose in milligrams per kilograms that would be needed to reach therapeutic trough levels of 5-8 ng/mL.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['SCID', 'severe combined immunodeficiency', 'maternal engraftment', 'aGVHD prophylaxis', 'sirolimus'], 'conditions': ['Severe Combined Immunodeficiency', 'Transplacental Maternal Engraftment', 'Stem Cell Transplant']}, 'referencesModule': {'references': [{'pmid': '10021471', 'type': 'BACKGROUND', 'citation': 'Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, Myers LA, Ward FE. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999 Feb 18;340(7):508-16. doi: 10.1056/NEJM199902183400703.'}, {'pmid': '17968328', 'type': 'BACKGROUND', 'citation': 'Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for primary immunodeficiency disease. Bone Marrow Transplant. 2008 Jan;41(2):119-26. doi: 10.1038/sj.bmt.1705890. Epub 2007 Oct 29.'}, {'pmid': '11535520', 'type': 'BACKGROUND', 'citation': 'Muller SM, Ege M, Pottharst A, Schulz AS, Schwarz K, Friedrich W. Transplacentally acquired maternal T lymphocytes in severe combined immunodeficiency: a study of 121 patients. Blood. 2001 Sep 15;98(6):1847-51. doi: 10.1182/blood.v98.6.1847.'}, {'pmid': '19744131', 'type': 'BACKGROUND', 'citation': 'Pulsipher MA, Wall DA, Grimley M, Goyal RK, Boucher KM, Hankins P, Grupp SA, Bunin N. A phase I/II study of the safety and efficacy of the addition of sirolimus to tacrolimus/methotrexate graft versus host disease prophylaxis after allogeneic haematopoietic cell transplantation in paediatric acute lymphoblastic leukaemia (ALL). Br J Haematol. 2009 Dec;147(5):691-9. doi: 10.1111/j.1365-2141.2009.07889.x. Epub 2009 Sep 10.'}, {'pmid': '20717025', 'type': 'BACKGROUND', 'citation': 'Cutler C, Antin JH. Sirolimus immunosuppression for graft-versus-host disease prophylaxis and therapy: an update. Curr Opin Hematol. 2010 Nov;17(6):500-4. doi: 10.1097/MOH.0b013e32833e5b2e.'}, {'pmid': '24497539', 'type': 'BACKGROUND', 'citation': "Pulsipher MA, Langholz B, Wall DA, Schultz KR, Bunin N, Carroll WL, Raetz E, Gardner S, Gastier-Foster JM, Howrie D, Goyal RK, Douglas JG, Borowitz M, Barnes Y, Teachey DT, Taylor C, Grupp SA. The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children's Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. Blood. 2014 Mar 27;123(13):2017-25. doi: 10.1182/blood-2013-10-534297. Epub 2014 Feb 4."}, {'pmid': '18481161', 'type': 'BACKGROUND', 'citation': 'Yong PL, Russo P, Sullivan KE. Use of sirolimus in IPEX and IPEX-like children. J Clin Immunol. 2008 Sep;28(5):581-7. doi: 10.1007/s10875-008-9196-1. Epub 2008 May 15.'}, {'pmid': '19543393', 'type': 'BACKGROUND', 'citation': 'Strauss L, Czystowska M, Szajnik M, Mandapathil M, Whiteside TL. Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin. PLoS One. 2009 Jun 22;4(6):e5994. doi: 10.1371/journal.pone.0005994.'}, {'pmid': '23165499', 'type': 'BACKGROUND', 'citation': 'Fujioka T, Tamaki H, Ikegame K, Yoshihara S, Taniguchi K, Kaida K, Kato R, Inoue T, Nakata J, Ishii S, Soma T, Okada M, Ogawa H. Frequency of CD4(+)FOXP3(+) regulatory T-cells at early stages after HLA-mismatched allogeneic hematopoietic SCT predicts the incidence of acute GVHD. Bone Marrow Transplant. 2013 Jun;48(6):859-64. doi: 10.1038/bmt.2012.232. Epub 2012 Nov 19.'}]}, 'descriptionModule': {'briefSummary': "Study Design: SCID infants receiving an unconditioned haploidentical transplant will be started on Sirolimus (0.05 mg/kg/day) day -5 for Acute Graft-Versus-Host Disease (aGVHD) prophylaxis. Sirolimus levels will be monitored with goal sirolimus trough level of 5-8 ng/mL. Patients will be monitored for signs of aGVHD as defined by UCSF SOP CL 221.06 through day +100. Sirolimus will be tapered once T-regulatory cell to CD4 effector cell ratio is \\> or = 9%.\n\nSetting: Inpatient BMT Unit Benioff Children's Hospital at UCSF Medical Center\n\nStudy Subjects: 15 infants with diagnosis of maternally engrafted T cells SCID by CA Newborn screen receiving unconditioned haploidentical HSCT\n\nMain Outcome Measures: Incidence of aGVHD (dermatitis, hepatitis, enteritis) as defined by SOP CL 221.06 by Day +100.\n\nHypothesis 1. Patients placed on sirolimus prophylaxis will have lower incidence of aGVHD compared to historical controls.\n\nHypothesis 2. Lower doses of sirolimus milligram per kilogram will be required to maintain goal troughs of 5-8 ng/mL."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '1 Year', 'minimumAge': '1 Day', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Infants diagnosed with SCID on CA newborn screen\n* Evidence of Maternal Engraftment\n* Unconditioned haploidentical hematopoeitic stem cell transplant\n\nExclusion Criteria:\n\n* Evidence of acute graft vs. host disease'}, 'identificationModule': {'nctId': 'NCT02177760', 'briefTitle': 'Sirolimus Prophylaxis for aGVHD in TME SCID', 'organization': {'class': 'OTHER', 'fullName': 'University of California, San Francisco'}, 'officialTitle': 'Sirolimus in Prevention of aGVHD in Maternally Engrafted (TME) Severe Combined Immunodeficiency (SCID) Infants Receiving Unconditioned Hematopoietic Stem Cell Transplant (HSCT)', 'orgStudyIdInfo': {'id': '14-13024'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sirolimus', 'description': 'Sirolimus (0.05 mg/kg/day) day -5 for aGVHD prophylaxis through day +100 or until T-regulatory cells \\>9% of CD4 effector cells; whichever comes first.', 'interventionNames': ['Drug: Sirolimus']}], 'interventions': [{'name': 'Sirolimus', 'type': 'DRUG', 'otherNames': ['Rapamune'], 'armGroupLabels': ['Sirolimus']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': "Benioff Children's Hospital at UCSF Medical Center", 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}], 'overallOfficials': [{'name': 'Chris Dvorak, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, San Francisco'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of California, San Francisco', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}