Cladribine Dose Escalation in Conditioning Regimen Prior to Allo-HSCT for Refractory Acute Leukemia and Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- estimation of the maximal tolerable dose,if any,and recommended phase II dose of cladribine administered as in combination with fludarabine and PK-guided IV busulfan prior Allo-HSCT for refractory acute leukemia and myelodysplastic syndrome (MDS)
研究概览
简要总结
The investigators focused on patients with refractory acute leukemia or MDS and designed a phase 1 trial of escalated cladribine doses in the Cla-Flu-Bu RTC regimen using PK-guided myeloablative busulfan doses. This scheme allows combining different optimization of RTC experienced over years (Flu-Bu RTC, PK-guided myeloablative busulfan doses, a second purine analog cladribine) to approach a specific platform to treat refractory diseases.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-70
- •ECOG 0 or 1
- •Acute leukemia (AML or ALL) without criteria for CR or high risk MDS without criteria for CR
- •Availability of a donor among following oHLA identical sibling oHaploidentical donor o10/10 or 9/10 allele-level HLA matched unrelated donor
- •Signed informed consent
- •Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen
排除标准
- •Contraindication for Allo-HSCT
- •Cord blood Allo-HSCT
- •Current active disease or positive serology for HIV, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen.
- •Renal failure with creatinine clearance < 30 ml/ min
- •Decompensated haemolytic anaemia
- •Hypersensitivity to an active substance or to any of the excipients
- •Acute urinary infection
- •Pre-existing haemorrhagic cystitis
- •Woman of childbearing potential not using an effective contraception .
- •Pregnant or lactating women
- •Any serious concurrent uncontrolled medical disorder
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
研究组 & 干预措施
Fludarabine-Cladribine-Busulfan conditioning regimen
干预措施: Fludarabine-Cladribine-Busulfan conditioning regimen (Drug)
结局指标
主要结局
estimation of the maximal tolerable dose,if any,and recommended phase II dose of cladribine administered as in combination with fludarabine and PK-guided IV busulfan prior Allo-HSCT for refractory acute leukemia and myelodysplastic syndrome (MDS)
时间窗: 30 days after Allo-HSCT
Occurrence ratio of dose-limiting toxicity defined as any grade ≥ 3 toxicity according to CTCAE (version 4.03 ) attributable to conditioning regimen (extra-medullary toxicity), considered to be related or probably related to the Cla-Fu-Bu RTC by the investigator.
次要结局
- Cumulative incidence of acute Graft versus host disease(100 days)
- Cumulative incidence of chronic Graft versus host disease(1 year)
- Cumulative incidence of relapse(1 year)
- Cumulative incidence of Non Relapse Mortality(100 days, 1 year)