This is a single center, randomized, open-label, phase II study to compare the efficacy of sirolimus combined with cyclosporin A (CsA) to sirolimus alone in Chinese subjects with aplastic anemia refractory/intolerant to CsA. The safety would also be evaluated. Patients would be randomized to receive sirolimus alone or sirolimus combined with CsA at a 1:3 ratio. Treatment with sirolimus will be started at 1-3 mg once daily orally, with a target trough blood concentration of 4-12 ng/ml. CsA will be given at 25-150 mg orally every 12 hours, with the dose adjusted based on renal function and trough concentration. For patients with normal renal function, the target trough concentration is approximately 150 ng/ml. For patients with impaired renal function, the cyclosporine A dose is reduced to 25-50 mg every 12 hours, aiming for recovery or stabilization of renal function. The hematological response rate and safety will be recorded and compared at 3 and 6 months after starting the study treatment (Week 13 and 25).
Age ≥ 18 years;
Diagnosed with acquired aplastic anemia (AA), excluding congenital AA;
At least one of the following criteria met at enrollment: hemoglobin < 100 g/L, platelets < 50 × 10⁹/L, or neutrophils < 1.0 × 10⁹/L;
No active infections;
Pancytopenia caused by other reasons, such as myelodysplastic syndrome (MDS);
Evidence of clonal hematopoietic system bone marrow diseases (e.g., MDS or acute myeloid leukemia, AML);
Paroxysmal nocturnal hemoglobinuria (PNH) clone ≥ 50%;
History of hematopoietic stem cell transplantation (HSCT) before enrollment;
Parallel
Sirolimus (Rapamune®)
DrugSirolimus 1-3 mg once daily orally, with a target trough blood concentration of 4-12 ng/ml.
Cyclosporin A (CsA)
DrugCyclosporine A 25-150 mg orally every 12 hours, with the dose adjusted based on renal function and trough concentration. For patients with normal renal function, the target trough concentration is approximately 150 ng/ml. For patients with impaired renal function, the cyclosporine A dose is reduced to 25-50 mg every 12 hours, aiming for recovery or stabilization of renal function.
Overall response rate (ORR) at 3 months
Overall Response Rate (ORR) is defined as the number of participants who meet the criteria of either complete response (CR) or partial response (PR)
Overall response rate (ORR) at 6 months
ORR will be evaluated after 6 months of treatment by measuring platelet, reticulocyte, hemoglobin, neutrophil and transfusion independence.
Changes in Hemoglobin in the Absence of Red Blood Cells Transfusion
The change in hematology values (hemoglobin) were evaluated
Changes in Platelet in the Absence of Platelet Transfusion
The change in hematology values (platelet) were evaluated
Duration of hematologic response
Time from the date of the start of the first response to the date of first relapse defined as again meeting criteria for aplastic anemia
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