Sirolimus in the Treatment of Refractory/Relapsed wAIHA
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Sirolimus.
- Who it may be relevant to
- Registry conditions: Warm Autoimmune Hemolytic Anemia. Basic parameters: 18 years — 90 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- China
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Sirolimus in the Treatment of Refractory/Relapsed Warm Autoimmune Hemolytic Anemia (AIHA)： a Phase 2 Prospective Trial
Overview
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
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.
Interventions
- Drug Sirolimus
Oral administration, 1-3 mg/d, sirolimus plasma concentration: 4-15 ng/mL
Primary outcome measures
- Overall response rate (ORR) and complete response rate (CRR) [Time frame: 3,6,12 months]
Secondary outcome measures (3)
- Number of participants with treatment-related adverse events and the number of relapses [Time frame: 12 months, end of the follow-up]
- Adverse events [Time frame: 3,6,12 months]
- Relapse rate [Time frame: 3,6,12 months]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
China · 1 center
- Peking Union Medical College Hospital — Beijing
Publications
- Jager U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, Jilma B, Kuter DJ, Michel M, Montillo M, Roth A, Zeerleder SS, Berentsen S. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev. 2020 May;41:100648. doi: 10.1016/j.blre.2019.100648. Epub 2019 Dec 5. PMID 31839434
- Bass GF, Tuscano ET, Tuscano JM. Diagnosis and classification of autoimmune hemolytic anemia. Autoimmun Rev. 2014 Apr-May;13(4-5):560-4. doi: 10.1016/j.autrev.2013.11.010. Epub 2014 Jan 11. PMID 24418298
- Hill QA, Stamps R, Massey E, Grainger JD, Provan D, Hill A; British Society for Haematology. The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol. 2017 Feb;176(3):395-411. doi: 10.1111/bjh.14478. Epub 2016 Dec 22. No abstract available. PMID 28005293
- Barcellini W, Fattizzo B. How I treat warm autoimmune hemolytic anemia. Blood. 2021 Mar 11;137(10):1283-1294. doi: 10.1182/blood.2019003808. PMID 33512406
- Birgens H, Frederiksen H, Hasselbalch HC, Rasmussen IH, Nielsen OJ, Kjeldsen L, Larsen H, Mourits-Andersen T, Plesner T, Ronnov-Jessen D, Vestergaard H, Klausen TW, Schollkopf C. A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol. 2013 Nov;163(3):393-9. doi: 10.1111/bjh.12541. Epub 2013 PMID 23981017
- Barcellini W, Fattizzo B, Zaninoni A, Radice T, Nichele I, Di Bona E, Lunghi M, Tassinari C, Alfinito F, Ferrari A, Leporace AP, Niscola P, Carpenedo M, Boschetti C, Revelli N, Villa MA, Consonni D, Scaramucci L, De Fabritiis P, Tagariello G, Gaidano G, Rodeghiero F, Cortelezzi A, Zanella A. Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of PMID 25232059
- Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, Manno CS, Casper J, Grupp SA, Teachey DT. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016 Jan 7;127(1):17-28. doi: 10.1182/blood-2015-07-657981. Epub 2015 Oct 26. PMID 26504182
- Li H, Ji J, Du Y, Huang Y, Gu H, Chen M, Wu R, Han B. Sirolimus is effective for primary relapsed/refractory autoimmune cytopenia: a multicenter study. Exp Hematol. 2020 Sep;89:87-95. doi: 10.1016/j.exphem.2020.08.001. Epub 2020 Aug 6. PMID 32771553
Identifiers
NCT: NCT05925023 · Sirolimus-1