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

May 29, 2025 updated by: Peking Union Medical College Hospital
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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sirolimus + cyclosporin A
Drug: Sirolimus (Rapamune®)
Sirolimus 1-3 mg once daily orally, with a target trough blood concentration of 4-12 ng/ml.
Drug: Cyclosporin A (CsA)
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.
Placebo Comparator: Sirolimus
Drug: Sirolimus (Rapamune®)
Sirolimus 1-3 mg once daily orally, with a target trough blood concentration of 4-12 ng/ml.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR) at 3 months
Time Frame: Week 12
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of hematologic response
Time Frame: by 6 months (all patients), at 12 months (responders only)
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
by 6 months (all patients), at 12 months (responders only)
Percentage of patients with clonal evolution to myelodysplasia, PNH, and acute leukemia
Time Frame: 12 months
Clonal evolution to myelodysplasia is defined as a new marrow cytogenic abnormality with or without characteristic dysplastic marrow findings. Evolution to leukemia is defined as greater than 20% peripheral blood and/or marrow blasts. Evolution to paroxysmal nocturnal hemoglobinuria (PNH) is defined as a clone at baseline < 10% that rose to greater than 50% on study.
12 months
Overall response rate (ORR) at 6 months
Time Frame: Week 24
ORR will be evaluated after 6 months of treatment by measuring platelet, reticulocyte, hemoglobin, neutrophil and transfusion independence.
Week 24
Changes in Hemoglobin in the Absence of Red Blood Cells Transfusion
Time Frame: Week 12
The change in hematology values (hemoglobin) were evaluated
Week 12
Changes in Platelet in the Absence of Platelet Transfusion
Time Frame: Week 12
The change in hematology values (platelet) were evaluated
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking Union Medical College Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 25, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 25, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 25, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 30, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • I-25PJ0215

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data would be accepted upon request

IPD Sharing Time Frame

10 years

IPD Sharing Access Criteria

Email request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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