Ignite Creation Date:
2025-12-24 @ 3:49 PM
Ignite Modification Date:
2026-01-22 @ 9:20 AM
Study NCT ID:
NCT02828592
Status:
RECRUITING
Last Update Posted:
2025-10-30
First Post:
2016-07-06
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000741', 'term': 'Anemia, Aplastic'}], 'ancestors': [{'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D000080983', 'term': 'Bone Marrow Failure Disorders'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C024352', 'term': 'fludarabine'}, {'id': 'D003520', 'term': 'Cyclophosphamide'}, {'id': 'D014916', 'term': 'Whole-Body Irradiation'}, {'id': 'C512542', 'term': 'thymoglobulin'}], 'ancestors': [{'id': 'D010752', 'term': 'Phosphoramide Mustards'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D063088', 'term': 'Phosphoramides'}, {'id': 'D009943', 'term': 'Organophosphorus Compounds'}, {'id': 'D011878', 'term': 'Radiotherapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 20}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2016-09-09', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-10', 'completionDateStruct': {'date': '2027-08-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-10-29', 'studyFirstSubmitDate': '2016-07-06', 'studyFirstSubmitQcDate': '2016-07-06', 'lastUpdatePostDateStruct': {'date': '2025-10-30', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2016-07-11', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2026-08-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant', 'timeFrame': '2 years', 'description': 'Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be \\<30%.'}], 'secondaryOutcomes': [{'measure': 'Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events', 'timeFrame': '2 years'}, {'measure': 'Determine the incidence of grade 2-4 and 3-4 acute graft versus host disease at 100 days post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course', 'timeFrame': '2 years'}, {'measure': 'Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course', 'timeFrame': '2 years'}, {'measure': 'Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points', 'timeFrame': '2 years'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['SAA'], 'conditions': ['Severe Aplastic Anemia']}, 'referencesModule': {'references': [{'pmid': '20018919', 'type': 'BACKGROUND', 'citation': 'Brodsky RA, Chen AR, Dorr D, Fuchs EJ, Huff CA, Luznik L, Smith BD, Matsui WH, Goodman SN, Ambinder RF, Jones RJ. High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood. 2010 Mar 18;115(11):2136-41. doi: 10.1182/blood-2009-06-225375. Epub 2009 Dec 16.'}, {'pmid': '24319167', 'type': 'RESULT', 'citation': 'Socie G. Allogeneic BM transplantation for the treatment of aplastic anemia: current results and expanding donor possibilities. Hematology Am Soc Hematol Educ Program. 2013;2013:82-6. doi: 10.1182/asheducation-2013.1.82.'}, {'pmid': '24319166', 'type': 'RESULT', 'citation': 'Young NS. Current concepts in the pathophysiology and treatment of aplastic anemia. Hematology Am Soc Hematol Educ Program. 2013;2013(1):76-81. doi: 10.1182/asheducation-2013.1.76.'}, {'pmid': '22517900', 'type': 'RESULT', 'citation': 'Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood. 2012 Aug 9;120(6):1185-96. doi: 10.1182/blood-2011-12-274019. Epub 2012 Apr 19.'}, {'pmid': '26359881', 'type': 'RESULT', 'citation': 'Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, Morris LE, Holland HK, Solomon SR. Comparison of Outcomes of Hematopoietic Cell Transplants from T-Replete Haploidentical Donors Using Post-Transplantation Cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 Allele-Matched Unrelated Donors and HLA-Identical Sibling Donors: A Multivariable Analysis Including Disease Risk Index. Biol Blood Marrow Transplant. 2016 Jan;22(1):125-33. doi: 10.1016/j.bbmt.2015.09.002. Epub 2015 Sep 7.'}, {'pmid': '25797174', 'type': 'RESULT', 'citation': 'Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. doi: 10.1016/j.bbmt.2015.03.003. Epub 2015 Mar 19.'}, {'pmid': '24842530', 'type': 'RESULT', 'citation': 'Bashey A, Solomon SR. T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor. Bone Marrow Transplant. 2014 Aug;49(8):999-1008. doi: 10.1038/bmt.2014.62. Epub 2014 May 19.'}, {'pmid': '2889870', 'type': 'RESULT', 'citation': 'Rozman C, Marin P, Nomdedeu B, Montserrat E. Criteria for severe aplastic anaemia. Lancet. 1987 Oct 24;2(8565):955-7. doi: 10.1016/s0140-6736(87)91432-2.'}, {'pmid': '22796534', 'type': 'RESULT', 'citation': 'Atta EH, de Sousa AM, Schirmer MR, Bouzas LF, Nucci M, Abdelhay E. Different outcomes between cyclophosphamide plus horse or rabbit antithymocyte globulin for HLA-identical sibling bone marrow transplant in severe aplastic anemia. Biol Blood Marrow Transplant. 2012 Dec;18(12):1876-82. doi: 10.1016/j.bbmt.2012.07.004. Epub 2012 Jul 11.'}]}, 'descriptionModule': {'briefSummary': 'Severe aplastic anemia is a rare and serious form of bone marrow failure related to an immune-mediated mechanism that results in severe pancytopenia and high risk for infections and bleeding. Patients with matched sibling donors for transplantation have a 80-90% chance of survival; however, a response rate with just immunosuppression for those patients lacking suitable HLA-matched related siblings is only 60%. With immunosuppression, only 1/3 of patients are cured, 1/3 are dependent on long term immunosuppression, and the other 1/3 relapse or develop a clonal disorder. Recent studies have shown that using a haploidentical donor for transplantation has good response rates and significantly lower rates of acute and chronic GVHD.', 'detailedDescription': 'Mismatched haploidentical donors will be identified for patients with severe aplastic anemia. These patients will undergo a preparative regimen of Fludarabine/Cyclophosphamide/TBI followed by haploidentical bone marrow transplantation. Post-transplant Cyclophosphamide will be administered on Days 3 \\& 4. Immunosuppression with Tacrolimus and MMF will begin on Day +5; MMF will be discontinued on Day +35 while Tacrolimus continues until Day +180. Investigators hypothesize that haploidentical transplantation with the above-mentioned preparative regimen will have a \\<30% graft failure rate. The one-sided exact Binomial test at 5% significance level will be used to test this hypothesis. The size of 20 patients provides the power of 92.5% for confirming the 30-day graft failure rate \\<30%.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '1 Year', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor who must have negative HLA cross-match in the host vs. graft direction\n* Age \\<= 65 years for previously treated and \\<= 75 years for previously treated patients\n* KPS \\>= 70%\n* Aplastic Anemia that meets the following criteria:\n\nPeripheral Blood (must fulfill 2 of 3):\n\n* \\<500 PMN/mm3\n* \\<20,000 platelets\n* absolute reticulocyte count \\<40,000/microL\n\nBone Marrow (must be either):\n\n* markedly hypocellular (\\<25% of normal cellularity)\n* moderately hypocellular with 70% non-myeloid precursors and patient meets peripheral blood criteria above\n\nExclusion Criteria:\n\n* poor cardiac function (LVEF \\<40%)\n* poor pulmonary function (FEV1 \\& FVC \\<50% predicted)\n* poor liver function (bili \\>= 2mg/dL)\n* poor renal function (creatinine \\>= 2.0mg/dL or creatinine clearance \\<40mL/min)\n* prior allogeneic transplant'}, 'identificationModule': {'nctId': 'NCT02828592', 'briefTitle': 'Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia', 'organization': {'class': 'OTHER', 'fullName': 'Northside Hospital, Inc.'}, 'officialTitle': 'A Study of T-Cell Replete, HLA-Mismatched Haploidentical Bone Marrow Transplantation With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia Lacking HLA-Matched Related Donor', 'orgStudyIdInfo': {'id': 'NSH 1158'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Flu/Cy/TBI', 'description': 'Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 \\& 4.', 'interventionNames': ['Drug: Fludarabine', 'Drug: Cyclophosphamide', 'Radiation: Total Body Irradiation', 'Drug: Rabbit ATG']}], 'interventions': [{'name': 'Fludarabine', 'type': 'DRUG', 'description': '30 mg/m2 IV QD x 5 days (Days -6 to -2)', 'armGroupLabels': ['Flu/Cy/TBI']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'description': '14.5 mg/kg/day IV x 2 doses (Days -6 \\& -5)', 'armGroupLabels': ['Flu/Cy/TBI']}, {'name': 'Total Body Irradiation', 'type': 'RADIATION', 'otherNames': ['TBI'], 'description': '300 cGy x1 dose (Day -1)', 'armGroupLabels': ['Flu/Cy/TBI']}, {'name': 'Rabbit ATG', 'type': 'DRUG', 'description': '1.5 mg/kg/day x 3 days (Days -3 to -1)', 'armGroupLabels': ['Flu/Cy/TBI']}, {'name': 'Cyclophosphamide', 'type': 'DRUG', 'description': 'Post-transplant: 50 mg/kg IV QD (Day +3 to +4)', 'armGroupLabels': ['Flu/Cy/TBI']}]}, 'contactsLocationsModule': {'locations': [{'zip': '30342', 'city': 'Atlanta', 'state': 'Georgia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Melhem Solh, MD', 'role': 'CONTACT', 'email': 'msolh@bmtga.com', 'phone': '404-255-1930'}], 'facility': 'Blood and Marrow Transplant Group of Georgia', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '30342', 'city': 'Atlanta', 'state': 'Georgia', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Melhem Solh, MD', 'role': 'CONTACT', 'email': 'msolh@bmtga.com', 'phone': '404-255-1930'}, {'name': 'Stacey Brown', 'role': 'CONTACT', 'email': 'stacey.brown@northside.com', 'phone': '404-851-8238'}, {'name': 'Scott Solomon, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'H. Kent Holland, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Asad Bashey, MD, PhD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Lawrence Morris, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Melhem Solh, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Northside Hospital', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}], 'centralContacts': [{'name': 'Melhem Solh, MD', 'role': 'CONTACT', 'email': 'msolh@bmtga.com', 'phone': '404-255-1930'}, {'name': 'Stacey Brown', 'role': 'CONTACT', 'email': 'stacey.brown@northside.com', 'phone': '404-851-8238'}], 'overallOfficials': [{'name': 'Melhem Solh, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Blood and Marrow Transplant Group of Georgia'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Northside Hospital, Inc.', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}