Reduced Post-transplant Cyclophosphamide Dose in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation for Hematological Malignancies: a Phase III Randomized Study
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 180
- 试验地点
- 2
- 主要终点
- GVHD-free, relapse-free, event-free survival (GREFS)
研究概览
简要总结
Phase III comparative, open-label, randomized (1:1) trial designed to evaluate the efficacy of reducing the total dose of PTCy to 70 mg/kg on GREFS compared to the standard dose of 100 mg/kg, in patients undergoing haploidentical HSCT for the treatment of a hematological malignancy, two years after HSCT.
详细描述
The primary endpoint is the assessment of the GREFS at 2 years after HSCT, a composite endpoint defined as the probability of survival without severe GVHD, relapse/progression of the hematological malignancy, or PTCy-associated adverse event, whichever comes first from transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Confirmed hematological malignancy with an indication for allogeneic HSCT
- •Presence of a haploidentical donor willing to donate PBSC
- •Patient planned to receive a thiotepa-based conditioning regimen
- •Provision of written informed consent Affiliation to a social security system (excluding "Aide Médicale d'État")
排除标准
- •Karnofsky performance status < 70%
- •Life expectancy < 1 month, as determined by the attending physician
- •Acute or chronic heart failure, defined as left ventricular ejection fraction < 40%
- •Pulmonary dysfunction with diffusion capacity < 50% of predicted values
- •Renal impairment with estimated glomerular filtration rate (eGFR) < 45 mL/min (calculated using the CKD-EPI formula)
- •Decompensated hemolytic anemia
- •Fanconi anemia and other DNA breakage repair disorders
- •Acute urothelial toxicity due to cytotoxic chemotherapy or radiotherapy
- •Obstruction of urinary outflow
- •Concomitant use with yellow fever vaccine and with live virus and bacterial vaccines
- •Combination with products containing Hypericum perforatum
- •Combination with medicines that are substrates for the multidrug efflux transporter P-glycoprotein (P-gp) or the organic anion transporter proteins (OATP) and for which elevated plasma concentrations are associated with serious and/or life-threatening events, e.g., bosentan, dabigatran etexilate and aliskiren
- •Active non-controlled infectious disease
- •Positive HIV status
- •Pregnancy, breast-feeding, or refusal to use effective contraception for the duration of the study and 6 months after the last treatment dose
- •Individuals under legal protection measures or unable to provide consent (e.g., severe neurological or psychiatric disorders, or deprivation of liberty by judicial or administrative decision)
- •Hypersensitivity to the active substance or any of the excipients
- •Concurrent participation in another investigational therapeutic study
- •Inability to comply with study procedures as assessed by the investigator based on objective criteria, including but not limited to:
- •Significant language barrier in the absence of adequate translation support
- •Social or geographic situation preventing follow-up and adherence to visit schedule
- •Ongoing substance abuse likely to interfere with protocol compliance
- •Documented cognitive or functional impairment not otherwise covered under legal protection
研究组 & 干预措施
Reduced dose
cyclophosphamide administered at 35mg/kg/day (Adjusted body weight) on days +3 and +4
干预措施: Cyclophosphamide 35mg/kg/day (Drug)
Standard dose
cyclophosphamide administered at 50mg/kg/day (Adjusted Body Weight) on days +3 and +4
干预措施: Cyclophosphamide 50mg/kg/day (Drug)
结局指标
主要结局
GVHD-free, relapse-free, event-free survival (GREFS)
时间窗: Day 0 to first occurrence of acute grade III-IV GVHD, severe chronic GVHD, relapse, death, grade 3-4 cardiac event, or grade 3-4 BK virus-associated HC (up to 24 months post-transplant); platelet recovery (>50 × 10^9/L) assessed until Day +60
The primary endpoint is the assessment of the GREFS at 2 years after HSCT, a composite endpoint defined as the probability of survival without severe GVHD, relapse/progression of the hematological malignancy, or PTCy-associated adverse event, whichever comes first from transplantation
GVHD-free, relapse-free, event-free survival (GREFS)
时间窗: From Day 0 until the occurrence of any of the following: acute grade III-IV GVHD, severe chronic GVHD, relapse, death, grade 3-4 cardiac event, or grade 3-4 BK virus-associated HC, whichever occurs first, assessed up to 24 months after transplantation, f
The primary endpoint is the assessment of the GREFS at 2 years after HSCT, a composite endpoint defined as the probability of survival without severe GVHD, relapse/progression of the hematological malignancy, or PTCy-associated adverse event, whichever comes first from transplantation
次要结局
- Cumulative incidence and severity of acute and chronic GVHD assessed according to the 2014 NIH criteria(From transplantation until the occurrence of GVHD or death from any cause, or up to 180 days after transplantation for acute GVHD, or up to 24 months for chronic GVHD, whichever occurs first)
- Overall survival (OS)(From transplantation until death from any cause or up to 24 months, whichever occurs first)
- Quality of life FACT-BMT(At 1, 3, 6, 12, and 24 months after HSCT)
- Toxicities, infection and hematogical recovery(From transplantation until the occurrence of the event, day +60 for hematological recovery, or up to 24 months for organ damage toxicities and infections, whichever occurs first)
- Cumulative incidence and severity of acute and chronic GVHD(From transplantation until the occurrence of GVHD or death from any cause, or up to 180 days after transplantation for acute GVHD, or up to 24 months for chronic GVHD, whichever occurs first)
- Non-relapse mortality(From transplantation until death without evidence of relapse or up to 24 months, whichever occurs first Description: NRM refers to death without evidence of disease relapse.)
- Cumulative incidence of relapse(From transplantation until the occurrence of relapse or up to 24 months, whichever occurs first)
- GVHD-free, relapse-free survival (GRFS)(From transplantation until the occurrence of acute grade III-IV GVHD, severe chronic GVHD, relapse, death, or up to 24 months, whichever occurs first)
- Cost-effectiveness(From transplantation until 2 years)
- Gut microbiota(Inclusion, Day 0, Day 15-35, Day 90)
- Cytokine profiles(Inclusion, Day 0, Day 15-35, Day 90, Day 365)
- Quality of life EQ-5D-5L(At 1, 3, 6, 12, and 24 months after HSCT)
- Disease-free survival (DFS)(At two years)