Sirolimus with or without cyclosporin A for Chinese adults with aplastic anemia who are refractory or intolerant to CsA

Efficacy and Safety of Sirolimus With or Without Cyclosporin A in Chinese Patients With Aplastic Anemia Refractory/Intolerant to Cyclosporin A

This trial will test whether adding cyclosporin A to sirolimus helps Chinese adults with aplastic anemia who did not respond to or could not tolerate cyclosporin A.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06802055 on ClinicalTrials.gov

What this trial studies

This single-center, randomized, open-label phase II trial in Beijing randomizes participants 1:3 to receive sirolimus alone or sirolimus plus cyclosporin A to compare hematologic response and safety. Sirolimus is started at 1–3 mg once daily with a target trough concentration of 4–12 ng/mL, while cyclosporin A is given every 12 hours (typically 25–150 mg) with dose adjustments for renal function and trough levels (≈150 ng/mL for normal renal function). Patients are assessed for hematologic response rates and adverse events at 3 and 6 months after starting treatment. The trial enrolls adults with acquired aplastic anemia who are refractory or intolerant to standard-dose cyclosporin A.

Who should consider this trial

Good fit: Adults (≥18) with acquired aplastic anemia who are refractory to or intolerant of cyclosporin A, meet cytopenia criteria, have ECOG 0–2, no active infection, and can give informed consent.

Not a fit: Patients with pancytopenia from other causes or clonal bone marrow diseases (e.g., MDS or AML), congenital aplastic anemia, active infections, or significant organ dysfunction are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve blood counts and reduce transfusion needs for patients who failed or could not tolerate cyclosporin A.

How similar studies have performed: Small series and nonrandomized reports have shown some benefit of sirolimus or mTOR inhibition in selected aplastic anemia patients, but randomized evidence for combining sirolimus with cyclosporin A is limited.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years;
2. Diagnosed with acquired aplastic anemia (AA), excluding congenital AA;
3. At least one of the following criteria met at enrollment: hemoglobin \< 100 g/L, platelets \< 50 × 10⁹/L, or neutrophils \< 1.0 × 10⁹/L;
4. At enrollment, meeting at least one of the following conditions:

   ① Cyclosporine A (CsA) ineffective: (CsA) used for at least 3 months without achieving partial response (PR), or disease relapse occurred;

   ② CsA intolerant: Unsuitable for standard dose CsA treatment due to adverse events or underlying conditions.
5. No active infections;
6. Not pregnant or breastfeeding;
7. Willing to sign the consent form;
8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

Exclusion Criteria:

1. Pancytopenia caused by other reasons, such as myelodysplastic syndrome (MDS);
2. Evidence of clonal hematopoietic system bone marrow diseases (e.g., MDS or acute myeloid leukemia, AML);
3. Paroxysmal nocturnal hemoglobinuria (PNH) clone ≥ 50%;
4. History of hematopoietic stem cell transplantation (HSCT) before enrollment;
5. Previous use of sirolimus or allergy to sirolimus;
6. Severe adverse events to CsA in the past, making it unsuitable for reuse;
7. Uncontrolled infection or bleeding with standard treatment;
8. Active infections with HIV, HCV, or HBV, liver cirrhosis, portal hypertension;
9. Any concurrent malignancy within the past 5 years, except for localized basal cell carcinoma of the skin;
10. History of thromboembolic events, myocardial infarction, or stroke (including antiphospholipid antibody syndrome), or current use of anticoagulants;
11. Pregnant or breastfeeding women;
12. Participation in other clinical trials within the past 3 months.

Where this trial is running

Beijing, Beijing Municipality

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Ziwei Liu

Conditions Aplastic Anaemia; Sirolimus; Relapsed/refractory aplastic anemia