Sirolimus in the Treatment of Refractory/Relapsed wAIHA

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Sirolimus
  Oral administration, 1-3 mg/d, sirolimus plasma concentration: 4-15 ng/mL

Первичные конечные точки

• Overall response rate (ORR) and complete response rate (CRR) [Срок оценки: 3,6,12 months]

Вторичные конечные точки (3)

• Number of participants with treatment-related adverse events and the number of relapses [Срок оценки: 12 months, end of the follow-up]
• Adverse events [Срок оценки: 3,6,12 months]
• Relapse rate [Срок оценки: 3,6,12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking Union Medical College Hospital — Пекин

Публикации

• 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

Идентификаторы

NCT: NCT05925023 · Sirolimus-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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