NCT05917405招募中2 期
FLUCLORIC: Randomized Multicentric Phase III Study Comparing the Efficacy of 2 Reduced Intensity Conditioning Regimens (Clofarabine/Busulfan vs Fludarabine/Busulfan) in Adults With AML and Eligible to Allogeneic Stem Cell Transplantation
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 302
- 试验地点
- 23
- 主要终点
- To compare 2-year OS between patients with AML in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT.
研究概览
简要总结
Relapse remains the main cause of death in patients with myeloid malignancies, especially after an allotransplant. Using drugs with higher anti-leukemic activity as part of the conditioning regimen is one of the strategies to decrease relapse incidence in this population. Retrospective studies have shown that clofarabine can achieve impressive results compared to the use of fludarabine in acute myeloid leukemia (AML) as part of the conditioning regimen. Confirming such results in a prospective manner would definitely establish the CloB2A2 as a superior reduced-intensity conditioning (RIC) regimen compared to the FB2A2 for AML patients.302 AML patients (151 in each arm) in complete remission at transplant will be included with the main objective to demonstrate a significant better 2-year overall survival for CloB2A2 cases (70% vs 55%). A cost-utility analysis and a cost-effectiveness analysis will be also performed as well as an assessment of the quality of life after transplant. Clofarabine will be furnished to all centers. The duration of the study will be 5 years with 3 years of inclusion and 2 years of follow-up for each patient.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years' old
- •De novo or secondary AML (according to ELN 2022 classification) in complete cytological remission at time of transplant (bone marrow blast count < 5%) or MDS/LAM with bone marrow blast count ≤ 5%
- •Patients in first or second line therapy are allowed
- •Patient eligible to a RIC regimen : patients aged ≥ 60 year old or <60 with co-morbidity(ies).
- •Patient with a related or an unrelated matched donor
- •Graft using only peripheral blood stem cells
- •Performance status ECOG 0 - 2
- •Who provide their written informed consent
- •Previous allograft allowed
- •Affiliated with French social security system or beneficiary from such system
- •Women must meet one of the following criteria at the time of inclusion:
- •use adequate contraceptive measures as recommended by the CTFG (Recommendations related to contraception and pregnancy testing in clinical trials v1.1; includes injectable implants, dual hormone birth control pills, intrauterine devices, abstinence from sex, or a sterilized partner), and have a negative pregnancy test (urine or serum pregnancy test) prior to receiving the first dose of study drug;
- •or be post-menopausal (over 50 years of age with amenorrhea for at least 12 months after discontinuation of all exogenous hormonal therapy)
- •or (if under 50 years of age) have been amenorrheic for at least 12 months after discontinuation of exogenous hormonal therapy and with luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels corresponding to post-menopausal levels
- •or have undergone irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (this operation must be documented).
- •Contraception methods must be prescribed using effective contraceptive methods during treatment and within 6 months for women of childbearing age (WOCB) and 6 months for men in case they have sexual relations with WOCB after the last dose of Fludarabine/Clofarabine.
排除标准
- •Pro-myelocytic leukemia
- •Patient eligible to a myeloablative conditioning regimen
- •Patient with haploidentical, mismatched unrelated donor or umbilical cord blood
- •Pregnant or breastfeeding woman or patient refusing contraceptive mesures
- •HIV positive
- •Active Hepatitis B or C
- •Left ventricular ejection fraction < 50%.
- •DLCOc <40%
- •Uncontrolled infection
- •Uncontrolled haemolytic anaemia
- •Creatinine clearance < 50 ml/min (evaluated by MDRD or CKDEPI).
- •Serum bilirubine > 30 mmol/l, Cytolysis > 5 the upper limit range
- •Previous or concurrent second malignancy except for adequately treated basal cell carcinoma of the skin, curatively treated in situ carcinoma of the cervix, curatively treated solid cancer, with no evidence of disease for at least 2 years
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Participation to another interventional study during the last month or expected participation to another interventional study during participation to the FLUCLORIC study.
研究组 & 干预措施
Experimental: CloB2 arm
Experimental
- 30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)
- 3.2mg/kg/day IV busulfan once daily for 2 days (day -5 and -4)
- ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1) Corticosteroids may be used in profilaxis
干预措施: Busulfan (Drug)
Experimental: CloB2 arm
Experimental
- 30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)
- 3.2mg/kg/day IV busulfan once daily for 2 days (day -5 and -4)
- ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1) Corticosteroids may be used in profilaxis
干预措施: ATG (Drug)
Experimental: CloB2 arm
Experimental
- 30 mg/m2/day IV clofarabine for 5 days (day-6 to day-2)
- 3.2mg/kg/day IV busulfan once daily for 2 days (day -5 and -4)
- ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1) Corticosteroids may be used in profilaxis
干预措施: Clofarabine (Drug)
Comparator: FB2A2 arm
Active Comparator
- 30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)
- 3.2 mg/kg/day IV busulfan once daily for 2 days (day -5 and -4)
- ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)
干预措施: Fludarabine (Drug)
Comparator: FB2A2 arm
Active Comparator
- 30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)
- 3.2 mg/kg/day IV busulfan once daily for 2 days (day -5 and -4)
- ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)
干预措施: Busulfan (Drug)
Comparator: FB2A2 arm
Active Comparator
- 30 mg/m2/day IV fludarabine for 5 days (day-6 to day-2)
- 3.2 mg/kg/day IV busulfan once daily for 2 days (day -5 and -4)
- ATG (Thymoglobuline®) 2.5 mg/Kg/day IV for 2 consecutive days (day -2 and -1)
干预措施: ATG (Drug)
结局指标
主要结局
To compare 2-year OS between patients with AML in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT.
时间窗: 2 years
OS is defined as the time from day 1 of conditioning to death or last follow-up for survivors.
次要结局
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: Engraftment, primary and secondary graft failure(day +30/42 and 2 years)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT:2-year NRM(2 years)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo- SCT: Minimal residual disease (MRD)(days +30 and +90)
- Comparison of infections after FB2A2 vs CloB2A2: bacterial, viral, parasitic and fungal(day+90)
- health benefit measurement in both treatment arms(Days -7, +30, +90, +180, +360 and +720.)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: Neutrophils and platelet recoveries(2 years)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT:-2-year relapse incidence(2 years)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT:Incidence of GVHD free relapse free survival (GRFS)(2 years)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo SCT:Chimerism(days +30, +60, +90)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT: 2-year DFS(2 years)
- Quality of life using the and FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant))(Days -7, +30, +90, +180 and +360)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo-SCT:Incidence of acute and chronic graft versus host disease (GVHD)(Day 90 and 2 years)
- Evaluation of economic efficiency of a CloB2A2 compared to a FB2A2 RIC regimen for allo-SCT, from a collective perspective (considering costs to the National Health Insurance system, hospital and patients)with a 24-month time horizon.(2 years)
- Comparison of Overall survival (OS) between patients in first vs second line therapy and impact of clofarabine vs fludarabine in each sub-group.(2 years)
- Comparison of occurence of Veno-occlusive disease between patients receiving clofarabine vs fludarabine.n day 0 and day+90/100(day+90)
- Safety assessment(2 years)
- Comparison of DFS between patients in first vs second line therapy and impact of clofarabine vs fludarabine in each sub-group.(2 years)
- Comparison of Overall survival (OS) between patients receiving a first vs a second allograft and impact of clofarabine vs fludarabine in each sub-group.(2 years)
- Comparison of DFS between patients receiving a first vs a second allograft and impact of clofarabine vs fludarabine in each sub-group.(2 years)
- comparison of the cost of graft hospitalization between the 2 arms(2 years)
- To compare between AML patients in complete remission receiving either a CloB2A2 or a FB2A2 RIC regimen for allo- SCT:Immune reconstitution(3, 6 and 12 months)
- Quality of life using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30)(Days -7, +30, +90, +180, +360 and +720)
研究者
研究点 (23)
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