Sirolimus in the Treatment of Refractory/Relapsed wAIHA

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05925023

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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, we plan to explore the efficacy and safety of sirolimus in the treatment of refractory/relapsed wAIHA.

Condition or Disease	Intervention/Treatment	Phase
Warm Autoimmune Hemolytic Anemia	Drug: Sirolimus	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [12 months]
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR).

Secondary Outcome Measures

Complete response rate (CRR [12 months]
CRR defined as the proportion of patients who met the criteria of complete response.
Adverse events [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.
Relapse rate [12 months]
Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years old.
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.
No response to glucocorticoid therapy or recurrence.
Baseline liver (ALT, AST) was less than 2 times the normal value.
No active infection; Not pregnant or breastfeeding.
Agree to sign the consent form.