Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
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Phase 2 |
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%.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Flu/Cy/TBI Fludarabine, Cyclophosphamide, TBI followed by bone marrow transplantation. Post-transplant Cyclophosphamide will be on Days 3 & 4. |
Drug: Fludarabine
30 mg/m2 IV QD x 5 days (Days -6 to -2)
Drug: Cyclophosphamide
14.5 mg/kg/day IV x 2 doses (Days -6 & -5)
Radiation: Total Body Irradiation
300 cGy x1 dose (Day -1)
Other Names:
Drug: Rabbit ATG
1.5 mg/kg/day x 3 days (Days -3 to -1)
Drug: Cyclophosphamide
Post-transplant: 50 mg/kg IV QD (Day +3 to +4)
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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Age <= 65 years for previously treated and <= 75 years for previously treated patients
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KPS >= 70%
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Aplastic Anemia that meets the following criteria:
Peripheral Blood (must fulfill 2 of 3):
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<500 PMN/mm3
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<20,000 platelets
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absolute reticulocyte count <40,000/microL
Bone Marrow (must be either):
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markedly hypocellular (<25% of normal cellularity)
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moderately hypocellular with 70% non-myeloid precursors and patient meets peripheral blood criteria above
Exclusion Criteria:
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poor cardiac function (LVEF <40%)
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poor pulmonary function (FEV1 & FVC <50% predicted)
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poor liver function (bili >= 2mg/dL)
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poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40mL/min)
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prior allogeneic transplant
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Blood and Marrow Transplant Group of Georgia | Atlanta | Georgia | United States | 30342 |
2 | Northside Hospital | Atlanta | Georgia | United States | 30342 |
Sponsors and Collaborators
- Northside Hospital, Inc.
Investigators
- Principal Investigator: Melhem Solh, MD, Blood and Marrow Transplant Group of Georgia
Study Documents (Full-Text)
None provided.More Information
Publications
- NSH 1158