Sirolimus in the Treatment of Refractory/Relapsed wAIHA

August 16, 2023 updated by: Chen Miao, Peking Union Medical College Hospital

Sirolimus in the Treatment of Refractory/Relapsed Warm Autoimmune Hemolytic Anemia (AIHA)： a Phase 2 Prospective Trial

Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by the destruction of red blood cells through warm or cold antibodies. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. Our previous study of sirolimus in refractory/relapsed AIHA and ES found an effective rate of 80%. Therefore, the investigators plan to explore the efficacy and safety of sirolimus in the treatment of refractory/relapsed wAIHA.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Based on the optimal autoantibody-RBC reactivity temperatures, AIHA is classified into warm type, cold type, and mixed type. AIHA can be further classified into primary or secondary in nature. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. The refractory/relapsed wAIHA patients have increased cardiovascular events, increased opportunities for infections, decreased quality of life, and even death. A prospective multi-institutional trial in autoimmune cytopenia found that 8 of 10 patients with AIHA and Evans syndrome respond to sirolimus. Our previous study of sirolimus in refractory/relapsed AIHA and ES also found an effective rate of approximately 80%. Since sirolimus is cheap and accessible, our findings may reduce the economic burden of patients and be a guide on the selection of second-line treatment drugs in refractory/relapsed wAIHA and Evans syndrome.

Study Type

Interventional

Enrollment (Estimated)

22

Phase

  • 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 Locations

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years old.
  2. Diagnosed as primary warm autoimmune hemolytic anemia or Evans syndrome (primary or secondary). There is no treatment indication of other systemic involvement in the original disease if secondary.
  3. No response to glucocorticoid therapy or recurrence.
  4. Baseline liver (ALT, AST) was less than 2 times the normal value.
  5. No active infection; Not pregnant or breastfeeding.
  6. Agree to sign the consent form.

Exclusion Criteria:

  1. Patients with connective tissue disease or other organs involvement
  2. Infection or bleeding that cannot be controlled by standard treatment.
  3. Active HIV, HCV or HBV infection or cirrhosis or portal hypertension.
  4. Progressed uncontrolled malignant tumors and lymphoma
  5. Cirrhosis or portal hypertension.
  6. Pregnant or breastfeeding.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sirolimus on refractory/relapsed wAIHA
A prospective research of the sirolimus efficiency on refractory/relapsed primary wAIHA patients. Sirolimus dosage: 1-3 mg/d with plasma concentration 4-15ng/mL. Medication time should last at least 6 months. After reaching the optimal response, responders continue to use sirolimus for 1 year, and then gradually reduce the dosage.
Drug: Sirolimus
Oral administration, 1-3 mg/d, sirolimus plasma concentration: 4-15 ng/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: 12 months
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR).
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete response rate (CRR
Time Frame: 12 months
CRR defined as the proportion of patients who met the criteria of complete response.
12 months
Adverse events
Time Frame: 12 months
Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.
12 months
Relapse rate
Time Frame: 12 months
Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR).
12 months

Collaborators and Investigators

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

Sponsor

Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

June 24, 2023

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

June 21, 2023

First Submitted That Met QC Criteria

June 21, 2023

First Posted (Actual)

June 29, 2023

Study Record Updates

Last Update Posted (Actual)

August 21, 2023

Last Update Submitted That Met QC Criteria

August 16, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Sirolimus-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Clinical Trials on Warm Autoimmune Hemolytic Anemia

Clinical Trials on Sirolimus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Vietnam

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe