Sirolimus in the Treatment of Refractory/Relapsed wAIHA

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Warm Autoimmune Hemolytic Anemia

Intervention / Treatment
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* Drug: Sirolimus


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: Patients with connective tissue disease or other organs involvement Infection or bleeding that cannot be controlled by standard treatment. Active HIV, HCV or HBV infection or cirrhosis or portal hypertension. Progressed uncontrolled malignant tumors and lymphoma Cirrhosis or portal hypertension. Pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sirolimus on refractory/relapsed wAIHA<br>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<br>* Oral administration, 1-3 mg/d, sirolimus plasma concentration: 4-15 ng/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | 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 | CRR defined as the proportion of patients who met the criteria of complete response. | 12 months | 
| Adverse events | 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 | Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR). | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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warm autoimmune hemolytic anemia, Evans syndrome, refractory/relapsed, sirolimus, efficacy