Upfront Related Donor Transplantation in Patients With Myelodisplatic Syndrome : a Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 55
- 主要终点
- Disease-free survival
研究概览
简要总结
Three recent prospective "transplant/no transplant" studies concluded to an advantage of OS with transplantation in patients with high or intermediate-2 IPSS risk (not significant in Kröger's study). No prospective randomized trial has assessed the pre-transplant therapy in MDS patients yet but some information can be extracted from these 3 recent studies. In the French study (n=162), 72% patients with a donor received HSCT, previously treated by hypomethylating agent (HMA) in 71% of them. There was a trend to a better survival in patients achieving a complete remission with pre-graft therapy (HR: 0.55, p=0.088) and higher risk of death in unresponsiveness patients transformed into AML (HR: 2.36, p=0.008). In Nakamura's study (n=384), 83% of patients with a donor were transplanted, previously treated by HMA in 68%2. The multivariable Cox model for Overall Survival (OS) and Leukemia-free survival showed an excess risk in patients treated by HMA. Moreover, responders still have a higher risk of mortality as compared to patients who did not receive any pre-graft therapy (HR: 2.417, p=0.0054). In the German study, the aim was to initiate azacytidine at inclusion and to transplant patients after 4 cycles if a donor was identified1. Among 170 registered patients, 162 initiated 5-aza but 36% of them were "lost during this pre-graft therapy" before allocation to "donor" or "no-donor" arm, for different reasons including death (n=12). After 4 cycles of 5-aza, 79/81 patients "donor arm" were transplanted. The multivariable analysis showed remission status did not influence OS. Those 3 previous clinical trials thus suggest that a substantial number of patients planned for transplantation are not transplanted nowadays while no evidence of HMA benefit before HSCT has been clearly identified. This phase 2 study aim to assess the feasibility of upfront HSCT in patients with high risk MDS in order to increase the probability to be transplanted and to achieve a subsequent remission and better survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 50 and ≤ 70 years
- •An HLA (Human Leukocyte Antigen) matched sibling donor or familial haplo-identical donor has been identified
- •The disease fulfills at least one of the following criteria:
- •Intermediate-2 or high risk according to classical International Prognostic Scoring System (IPSS)
- •Intermediate-1 risk if marrow fibrosis > grade I or poor risk cytogenetics according to R IPSS or classified high or very high risk according to Revised International Prognostic Scoring System (R IPSS) or if the MDS is therapy-related neoplasm
- •Usual criteria for Hematopoietic Stem Cell Transplantation (HSCT):
- •Eastern Cooperative Oncology Group Score (ECOG) ≤ 2
- •No severe and uncontrolled infection
- •Cardiac function compatible with high dose of cyclophosphamide Left Ventricular Function (LVF) > 50%
- •Adequate organ function: ASAT and ALAT ≤ 2.5N, total bilirubin ≤ 2N, creatinine clearance ≥ 30 ml/min (according to Cockroft formula)
- •In case of transplantation with a haploidentical donor, absence of donor specific antibody (DSA) detected in the patient with a MFI >1000 (antibodies directed towards the distinct haplotype between donor and recipient)
- •Contraception methods must be prescribed for women of childbearing age during all the study. If cyclophosphamide is used, effective contraceptive methods for men during all their participation in the study
- •With health insurance coverage
- •With a written informed consent signed
排除标准
- •Marrow blast > 15% at time of inclusion
- •MDS with excess blast >10% and NPM1 mutation or a recurrent genetic abnormality related to Acute Myeloid Leukemia (AML) (WHO 2022)
- •Chemotherapy (AML like intensive chemotherapy or demethylating agent) to treat MDS at the current stage
- •Disponibility of an unrelated donor 10/10 (MUD) in absence of geno-identical donor
- •Patient with uncontrolled infection
- •Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix
- •Renal failure with creatinine clearance <30ml / min (according to Cockroft formula)
- •With contraindications to treatments used during the research
- •Uncontrolled coronary insufficiency, recent myocardial infarction <6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction <50%
- •With heart failure according to NYHA (II or more)
- •Patient with seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR Hepatitis B Virus or Hepatitis C Virus
- •Yellow fever vaccine or any alive vaccine within 2 months before transplantation
- •Pregnancy (β-HCG positive) or breast-feeding
- •Who have any debilitating medical or psychiatric illness, which would preclude giving well understand informed consent or optimal treatment and follow-up
- •Under protection by law (tutorship or curatorship)
结局指标
主要结局
Disease-free survival
时间窗: 2 years after transplantation
次要结局
- Cumulative incidence of transformation into acute myeloid leukemia from inclusion(2 years after inclusion)
- Percentage of engraftment(3 months after transplantation)
- Overall survival(2 years after transplantation)
- Non-relapse mortality(2 years after transplantation)
- Incidence of acute Graft versus Host Disease (GvHD) and grading(100 days after transplantation)
- Incidence of chronic GvHD and grading(2 years after transplantation)
- Percentage of graft failure(2 years after transplantation)
- Incidence of severe infections(24 months after transplantation)
- Incidence of cardiac events(3 months after transplantation)