Severe Aplastic Anemia
Conditions
Keywords
SAA
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%.
Interventions
DRUGFludarabine
30 mg/m2 IV QD x 5 days (Days -6 to -2)
DRUGCyclophosphamide
14.5 mg/kg/day IV x 2 doses (Days -6 & -5)
RADIATIONTotal Body Irradiation
300 cGy x1 dose (Day -1)
DRUGRabbit ATG
1.5 mg/kg/day x 3 days (Days -3 to -1)
Sponsors
Northside Hospital, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events | 2 years |
| 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 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 |
Countries
United States
Contacts
Primary ContactMelhem Solh, MD
Backup ContactStacey Brown
Outcome results
None listed