Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen

Официальное название

Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen for Patients With Acute B Cell Lymphoblast Leukemia Underwenting Haploidenticl Peripheral Blood Stem Cell Transplantation

Обзор

The purpose of this study is to determine the efficacy and safety of Ruxolitinib and Chidamide intensified conditioning regimen in patients with Acute B cell Lymphoblast leukemia Underwenting Haploidenticl Peripheral blood Stem Cell Transplantation.

Подробное описание

Haploidenticl Peripheral blood Stem Cell Transplantation should be offered to eligible patients with Acute B cell Lymphoblast leukemia whenever feasible. To further improve the outcome of transplantation patients with Acute B cell Lymphoblast leukemia, we developed a modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide. In this study, we tested the efficacy and feasibility of the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide in patients with Acute B cell Lymphoblast leukemia undergoing allogeneic peripheral blood stem cell transplantation.

Вмешательства

• Препарат Ruxolitinib combined with Chidamide.
  Drug: modified By/Cy conditioning regimen intensified by Ruxolitinib and Chidamide . Day -15 # Ruxolitinib 70mg bid, Chidamide 30 mg once; Day -14 # Ruxolitinib 70mg bid; Day -13 # Ruxolitinib 70mg bid; Day -12 # Ruxolitinib 70mg bid, Chidamide 30 mg once; Day -11 # Ruxolitinib 70mg bid; Day-10# Cytarabine 4g/m2/day CI , Ruxolitinib 60mg bid; Day- 9# Cytarabine 4g/m2/day CI, Ruxolitinib 60mg bid; Day- 8 # Busulfan 0.8mg/ kg Q6h iv, Ruxolitinib 50mg bid, Chidamide 30 mg once; Day- 7# Busulfan 0.

Первичные конечные точки

• Proportion of participants relapse as assessed by NCCN (National Comprehensive Cancer Network ) criteria [Срок оценки: 365 days after transplantation]

Вторичные конечные точки (7)

• DFS(disease-free survival ) [Срок оценки: 365 days after transplantation]
• TRM(treatment-related mortality ) [Срок оценки: 365 days after transplantation]
• Proportion of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria) [Срок оценки: 365 days after transplantation]
• Proportion of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria) [Срок оценки: 365 days after transplantation]
• OS(overall survival ) [Срок оценки: 365 days after transplantation]
• Failure-free survival (FFS) [Срок оценки: 365 days after transplantation]
• infection rate [Срок оценки: 365 days after transplantation]

Критерии участия

Критерии включения

• high risk acute B cell lymphoblastic leukemia with the indications for allogeneic transplantation;
• Have matched sibling donors, ≥8/10 HLA matched unrelated donors or haploidentical donors
• All patients should aged 12 to 65 years;
• Liver function: ALT and AST≤2.5 times the upper limit of normal , bilirubin≤2 times the upper limit of normal;
• Renal function: creatinine ≤the upper limit of normal;
• Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
• Have signed informed consent.

Критерии исключения

• pregnant women;
• Patients with mental illness or other states unable to comply with the protocol;
• ALL patients with Ph positive;

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

• Chinese PLA General Hospital — Пекин

Публикации

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• Shi Y, Jia B, Xu W, Li W, Liu T, Liu P, Zhao W, Zhang H, Sun X, Yang H, Zhang X, Jin J, Jin Z, Li Z, Qiu L, Dong M, Huang X, Luo Y, Wang X, Wang X, Wu J, Xu J, Yi P, Zhou J, He H, Liu L, Shen J, Tang X, Wang J, Yang J, Zeng Q, Zhang Z, Cai Z, Chen X, Ding K, Hou M, Huang H, Li X, Liang R, Liu Q, Song Y, Su H, Gao Y, Liu L, Luo J, Su L, Sun Z, Tan H, Wang H, Wang J, Wang S, Zhang H, Zhang X, Zhou D PMID 28298231
• Savino AM, Sarno J, Trentin L, Vieri M, Fazio G, Bardini M, Bugarin C, Fossati G, Davis KL, Gaipa G, Izraeli S, Meyer LH, Nolan GP, Biondi A, Te Kronnie G, Palmi C, Cazzaniga G. The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL. Leukemia. 2017 Nov;31(11):2365-2375. doi: 10.1038/leu.2017.93. Epub 2017 Mar 23. PMID 28331226
• Ding YY, Stern JW, Jubelirer TF, Wertheim GB, Lin F, Chang F, Gu Z, Mullighan CG, Li Y, Harvey RC, Chen IM, Willman CL, Hunger SP, Li MM, Tasian SK. Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure. Haematologica. 2018 Sep;103(9):e427-e431. doi: 10.3324/haematol.2018.192088. Epu PMID 29773603
• Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Kloble P, Oswald F, Borggrefe T. HDAC3 functions as a positive regulator in Notch signal transduction. Nucleic Acids Res. 2020 Apr 17;48(7):3496-3512. doi: 10.1093/nar/gkaa088. PMID 32107550

Идентификаторы

NCT: NCT05088226 · S2020-483-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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