Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
- Conditions
- Severe Aplastic Anemia
- Interventions
- Registration Number
- NCT02828592
- Lead Sponsor
- Northside Hospital, Inc.
- Brief Summary
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.
- Detailed Description
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%.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 20
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Flu/Cy/TBI Total Body Irradiation Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 \& 4. Flu/Cy/TBI Cyclophosphamide Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 \& 4. Flu/Cy/TBI Fludarabine Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 \& 4. Flu/Cy/TBI Rabbit ATG Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 \& 4.
- Primary Outcome Measures
Name Time Method Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant 2 years Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be \<30%.
- Secondary Outcome Measures
Name Time Method 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 Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events 2 years 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 Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points 2 years
Trial Locations
- Locations (2)
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Blood and Marrow Transplant Group of Georgia
🇺🇸Atlanta, Georgia, United States