Severe Aplastic Anemia Clinical Trial
Official title:
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
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.
Status | Recruiting |
Enrollment | 20 |
Est. completion date | August 31, 2026 |
Est. primary completion date | August 31, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Year to 75 Years |
Eligibility | Inclusion Criteria: - 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 - Age <= 65 years for previously treated and <= 75 years for previously treated patients - KPS >= 70% - Aplastic Anemia that meets the following criteria: Peripheral Blood (must fulfill 2 of 3): - <500 PMN/mm3 - <20,000 platelets - absolute reticulocyte count <40,000/microL Bone Marrow (must be either): - markedly hypocellular (<25% of normal cellularity) - moderately hypocellular with 70% non-myeloid precursors and patient meets peripheral blood criteria above Exclusion Criteria: - poor cardiac function (LVEF <40%) - poor pulmonary function (FEV1 & FVC <50% predicted) - poor liver function (bili >= 2mg/dL) - poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40mL/min) - prior allogeneic transplant |
Country | Name | City | State |
---|---|---|---|
United States | Blood and Marrow Transplant Group of Georgia | Atlanta | Georgia |
United States | Northside Hospital | Atlanta | Georgia |
Lead Sponsor | Collaborator |
---|---|
Northside Hospital, Inc. |
United States,
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 Transp — View 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 — View 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 — View 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. — View 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. — View 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. — View 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. — View 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 — View 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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant | Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be <30%. | 2 years | |
Secondary | Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events | 2 years | ||
Secondary | 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 | 2 years | ||
Secondary | Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course | 2 years | ||
Secondary | Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points | 2 years |
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