At a glance
ClinicalIndex Comparison Record- ✓Severe aplastic anemia confirmed by bone marrow cellularity <30% (excluding lymphocytes)
- ✓At least two cytopenias: ANC <500/µL, platelets <20,000/µL, or reticulocytes <60,000/µL
- ✓Refractory to prior h-ATG/CsA (persistent cytopenias at 3 months) or suboptimal response (platelets/reticulocytes <50,000/µL at 3 months)
- ✓Age ≥2 years
- ✕Fanconi anemia
- ✕Clonal disorder on cytogenetics (unless super severe ANC <200/µL pending results, then off study if later identified)
- ✕Prior rabbit ATG or high-dose cyclophosphamide (≥200 mg/kg equivalent)
- ✕Active, uncontrolled infection
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
A Randomized Trial of Immunosuppression in Aplastic Anemia Patients With Refractory Pancytopenia or Suboptimal Hematologic Response After h-ATG/CsA Treatment
In Brief
A Phase 2 clinical trial evaluating Campath-1H, r-ATG, and 1 other intervention for Aplastic Anemia. Completed, enrolled 54 participants across 1 site.
Detailed Summary
Severe aplastic anemia, characterized by pancytopenia and a hypocellular bone marrow, is effectively treated by immunosuppressive therapy, usually a combination of antithymocyte globulin (ATG) and cyclosporine (CsA). Survival rates following this regimen are equivalent to those achieved with allogeneic stem cells transplantation. However, approximately 1/3 of patients will not show blood count improvement after ATG/CsA. General experience and small pilot studies have suggested that such patients may benefit from further immunosuppression. Furthermore, analysis of our own clinical data suggest that patients with poor blood count responses to a single course of ATG, even when transfusion-independence is achieved, have a markedly worse prognosis than patients with robust hematologic improvement. The management of such cases is uncertain. This study will enroll patients who are either refractory to h-ATG (continued severe pancytopenia) or who have only modest improvement in blood counts (weak hematologic responders) to receive a further immunosuppressive therapy, delivered either as rabbit ATG (Thymoglobulin, r-ATG) or a humanized monoclonal antibody to T-cells, alemtuzumab (Campath-1H ). Primary endpoint will be response rate at 3 months defined as no longer meeting criteria for severe aplastic anemia. Relapse, robustness of hematopoietic recovery at 3 months, survival and clonal evolution to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia and acute leukemia will be the secondary endpoints.
Study Details
Timeline
Interventions
Campath-1H IV 10 days. Adults:10mg/day (children:0.2mg/kg/day).
Rabbit ATG 3.5mg/kg/day for consecutive 5 days
CsA 10mg/kg/day orally twice daily for 6 months (15mg/kg/day for children under 12 yrs.