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

NCT06802055 | Recruiting Phase 2 DMC

• 1 other identifier: I-25PJ0215
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Aplastic Anaemia

Keywords

Sirolimus; Relapsed/refractory aplastic anemia

Outcome Measures

Primary Outcomes (1)

• 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)

  Week 12

Secondary Outcomes (5)

• Overall response rate (ORR) at 6 months

  Week 24

• Changes in Hemoglobin in the Absence of Red Blood Cells Transfusion

  Week 12

• Changes in Platelet in the Absence of Platelet Transfusion

  Week 12

• Duration of hematologic response

  by 6 months (all patients), at 12 months (responders only)

• Percentage of patients with clonal evolution to myelodysplasia, PNH, and acute leukemia

  12 months

Study Arms (2)

Sirolimus + cyclosporin A

EXPERIMENTAL

Drug: Sirolimus (Rapamune®); Drug: Cyclosporin A (CsA)

Sirolimus

PLACEBO COMPARATOR

Drug: Sirolimus (Rapamune®)

Interventions

Sirolimus (Rapamune®) DRUG

Sirolimus 1-3 mg once daily orally, with a target trough blood concentration of 4-12 ng/ml.

Sirolimus; Sirolimus + cyclosporin A

Cyclosporin A (CsA) DRUG

Cyclosporine 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.

Sirolimus + cyclosporin A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.
• No active infections;
• Not pregnant or breastfeeding;
• Willing to sign the consent form;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

You may not qualify if:

• 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;
• Previous use of sirolimus or allergy to sirolimus;
• Severe adverse events to CsA in the past, making it unsuitable for reuse;
• Uncontrolled infection or bleeding with standard treatment;
• Active infections with HIV, HCV, or HBV, liver cirrhosis, portal hypertension;
• Any concurrent malignancy within the past 5 years, except for localized basal cell carcinoma of the skin;
• History of thromboembolic events, myocardial infarction, or stroke (including antiphospholipid antibody syndrome), or current use of anticoagulants;
• Pregnant or breastfeeding women;
• Participation in other clinical trials within the past 3 months.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Sirolimus; Cyclosporine

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Ziwei Liu

CONTACT

+8613811615392; liuzw10@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2025
• First Posted: January 30, 2025
• Study Start: January 25, 2025
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 10 years
• Access Criteria: Email request

Locations

CN (1)