Haplo-HSCT for Myelofibrosis

Официальное название

Haploidentical Hematopoietic Stem Cell Transplantation for the Treatment of Myelofibrosis: A Prospective, Single-center Study

Обзор

Myelofibrosis (MF) is a myeloproliferative neoplasm causing bone marrow failure and high risk of leukemia transformation. JAK2 inhibitors improve symptoms but do not cure MF. Allogeneic stem cell transplantation (allo-HSCT) is the only potential cure, though limited donor availability restricts access. Haploidentical transplantation shows promise but associated with higher graft failure and treatment related mortality. We recently developed a novel regimen of haplo-SCT for MF. This study aims to investigate this novel protocol in a prospective trial to improve MF outcomes.

Подробное описание

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells, reactive hyperplasia of bone marrow stromal cells, and secondary inflammation and fibrosis, leading to progressive bone marrow failure and a high risk of acute myeloid leukemia transformation, with a median survival of about 6 years. While JAK2 inhibitors like ruxolitinib have been approved to improve symptoms and survival in MF patients, they do not provide a cure. Allogeneic stem cell transplantation (allo-HSCT) remains the only potential cure, but limited availability of matched sibling and unrelated donors often prevents patients from receiving this treatment. Haploidentical stem cell transplantation has shown good efficacy in leukemia but is less studied in MF, possibly due to concerns about graft failure, complications, and high transplant-related mortality. Our team has applied a novel haploidentical transplantation protocol for treating MF, which has shown promising results in preliminary observations. This study aims to further validate the effectiveness of this protocol through a prospective clinical trial, potentially establishing an effective approach for HSCT in MF and improving overall transplant outcomes.

Вмешательства

• Процедура Haploidentical hematopoietic stem cell transplantation
  This is a single-arm study in which all patients will undergo haploidentical hematopoietic stem cell transplantation for the treatment of myelofibrosis. Pre-transplant Evaluation: Evaluation includes status of primary Disease, donor specific antibodies (DSA), organ function (assessments for heart, liver, lungs, kidneys, and the nervous system), and Spleen size. Transplantation Protocol: Conditioning Regimen: Dac/TT/Bu/Flu/ATG regimen: Decitabine 100 mg/m², on day -12. Thiotepa (TT) 5 mg/kg

Первичные конечные точки

• Cumulative incidence of Good graft function at day 60 [Срок оценки: Assessment at 60 days post-transplantation]

Вторичные конечные точки (11)

• Transplant-related mortality [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.]
• overall survival [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.]
• Cumulative Incidence of Relapse [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.]
• Incidence of GVHD [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.]
• Disease-free survival [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 36 months post-treatment.]
• Neutrophil Engraftment [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.]
• Platelet Engraftment [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 60 days post-treatment.]
• Graft failure [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 28 days post-treatment.]
• Toxicity of conditioning [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 30 days post-treatment.]
• Grade of Bone Fibrosis [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.]
• Spleen Response [Срок оценки: From baseline assessment at enrollment to the follow-up assessment at 12 months post-treatment.]

Критерии участия

Критерии включения

• Primary disease type: Myelofibrosis (including primary myelofibrosis and myelofibrosis secondary to polycythemia vera or essential thrombocythemia).
• No matched sibling donor or unrelated donor, with the availability of a haploidentical donor.
• Signed informed consent.

Критерии исключения

• Active infection
• Very poor performance status (ECOG score > 2)
• Estimated survival time < 30 days
• Patient or family unable to cooperate
• Considered unsuitable after discussion

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 University People's Hospital — Пекин

Публикации

• Polverelli N, Hernandez-Boluda JC, Czerw T, Barbui T, D'Adda M, Deeg HJ, Ditschkowski M, Harrison C, Kroger NM, Mesa R, Passamonti F, Palandri F, Pemmaraju N, Popat U, Rondelli D, Vannucchi AM, Verstovsek S, Robin M, Colecchia A, Grazioli L, Damiani E, Russo D, Brady J, Patch D, Blamek S, Damaj GL, Hayden P, McLornan DP, Yakoub-Agha I. Splenomegaly in patients with primary or secondary myelofibros PMID 36493799
• Cervantes F, Dupriez B, Passamonti F, Vannucchi AM, Morra E, Reilly JT, Demory JL, Rumi E, Guglielmelli P, Roncoroni E, Tefferi A, Pereira A. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol. 2012 Aug 20;30(24):2981-7. doi: 10.1200/JCO.2012.42.0240. Epub 2012 Jul 23. PMID 22826273
• Gangat N, Tefferi A. Myelofibrosis biology and contemporary management. Br J Haematol. 2020 Oct;191(2):152-170. doi: 10.1111/bjh.16576. Epub 2020 Mar 20. PMID 32196650

Идентификаторы

NCT: NCT06674382 · 2024PHB400-001 · Peking University

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗