2023-504555-27-00招募中3 期
Phase III study comparing GVHD prophylaxis with ATG-thymoglobulin to ATLG-grafalon in elderly patients with acute myeloid leukemia or myelodysplastic syndrome and receiving an allogeneic hematopoietic stem cell transplantation with a 10/10 HLA matched unrelated donor following a reduced intensity conditioning regimen by fludarabine-treosulfan (OPTISAGE)
Assistance Publique Hopitaux De Paris, Assistance Publique Hopitaux De Paris23 个研究点 分布在 1 个国家目标入组 324 人开始时间: 2023年9月29日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 324
- 试验地点
- 23
- 主要终点
- Incidence of grade II-IV acute GVHD according to the MAGIC classification (Appendix 19.9 section 1) at day 100 post-transplantation.
研究概览
简要总结
To compare the incidence of grade II-IV acute GVHD at day 100 post-transplantation in MDS or AML patients transplanted with a 10/10 matched unrelated donor (MUD) following a reduced intensity conditioning with fludarabine-treosulfan between patients receiving a GVHD prophylaxis with ATG-thymoglobulin versus ATLG-grafalon
研究设计
- 分配方式
- Randomized
- 主要目的
- Optisage
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 50 and ≤ 70 years
- •Patient between 50 and 55 years should be unfit for a myeloblative conditioning
- •AML requiring allogeneic stem cell transplantation (intermediate or high risk AML) in complete cytologic response (CR1 or above) or MDS requiring allogeneic stem cell transplantation (IPSS≥ 1.5 or IPSS-R > 4.5 or IPSS-R > 3-4.5 with risk features [rapid blast increase, life-threatening neutropenia (<0.3 G/L) or thrombopenia (<30G/L) or high transfusion needs (>2/month for 6 months)]
- •Without an HLA matched related donor
- •Having an identified matched HLA 10/10 unrelated donor
- •With usual criteria for HSCT: a) ECOG performans status ≤ 2 ; b) No severe and uncontrolled infection ; c) Cardiac left ventricular ejection fraction ≥50% ; d) Lung DLCO > 40% ; e) Adequate organ function: ASAT and ALAT ≤ 3N, total bilirubin ≤ 2N, creatinine clearance ≥ 50 mL/min (except if those abnormalities are linked to the hematological disease)
- •With health insurance coverage
- •Having signed a written informed consent
- •Contraception methods must be prescribed during all the duration of the research. NB: The authorized contraceptive methods are: For women of childbearing age and in absence of permanent sterilization: oral, intravaginal or transdermal combined hormonal contraception; oral, injectable or implantable progestogen-only hormonal contraception; intrauterine device (IUD); intrauterine hormonal releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence (only if this is the preferred and usual lifestyle of the participants). For men in absence of permanent sterilization: sexual abstinence, condoms
排除标准
- •Carcinoma in the last 5 years (except basal cell carcinoma of the skin or “in situ” carcinoma of the cervix)
- •Yellow fever vaccine and all others live virus vaccines within 2 months before transplantation
- •Heart failure according to NYHA (II or more) or Left ventricular ejection fraction < 50%.
- •Lung DLCO ≤ 40%
- •Preexisting acute hemorrhagic cystitis
- •Renal failure with creatinine clearance < 50ml / min
- •Pregnancy (β-HCG positive) or breast-feeding
- •Any contraindications mentioned in the SmPC of all auxiliary medicinal products planned to be used in the trial: cyclosporine, mycophenolate mofetil, fludarabine, treosulfan
- •Patients with any debilitating medical or psychiatric illness, which would preclude the realization of the SCT or the understanding of the protocol
- •Patient under state medical aid
- •Patient under legal protection (protection of the court, or in curatorship or guardianship)
- •For Grafalon : Any contraindications mentioned in the SmPC of GRAFALON
- •For Thymoglobulin : Hypersensitivity to rabbit proteins or to any of the excipients
- •Participation in other clinical trials on medicinal products for human use or being in the exclusion period at the end of a previous study
- •Uncontrolled infection
- •Seropositivity for HIV or HTLV-1 or active hepatitis B or C
结局指标
主要结局
Incidence of grade II-IV acute GVHD according to the MAGIC classification (Appendix 19.9 section 1) at day 100 post-transplantation.
Incidence of grade II-IV acute GVHD according to the MAGIC classification (Appendix 19.9 section 1) at day 100 post-transplantation.
次要结局
- Number of days of hospitalization for the transplant and after the hospitalization for transplantation related complications until M12
- Incidence and severity of VOD at D+100
- Lymphocyte counts on standard blood counts before conditioning (D-7)
- Late acute GvHD, overlap syndromes and chronic GvHD at D+120.
- Hematopoietic recoveries: at least 7 consecutive days with neutrophils > 0.5 G/L, with platelets > 20 G/L
- Immune reconstitution by analyzing T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood at M1, D+100, M6, M12 and M24 post-transplantation
- Chimerism at M1, D+100, M6, M12
- Grade I acute GVHD incidence (Appendix 19.9 section 1) and acute GvHD treatments: first line treatment, response to steroids, treatment courses for refractory acute GVHD
- Chronic GvHD incidence (date and grading) at M12 and M24 (NIH classification, Appendix 19.9 section 4)
- Relapse incidence at M12 and M24 (relapse will be defined by the reappearance of leukemic cells or MDS features after allo-HSCT in the bonne marrow (cytology +/- cytogenetic analysis from bone marrow aspiration) or extra-medullary sites (proven by a biopsy).
- Progression free survival at M12 and M24
- Severe infections (CTAE grade 3-4) at D+100 and M12 will be fully described
- Incidences of CMV and EBV reactivations at D+100, M6 and M12
- Non-relapse mortality at M6, M12 and M24
- Overall survival at M12 and M24
- GVHD and relapse free survival (GRFS) defined by being alive without disease relapse and without having developed acute grade III-IV or severe chronic GVHD
- Health-related Quality of life, assessed by using theFACT-BMT-v4 questionnaire at inclusion and at D+100, M6, M12 post-transplantation
研究者
Pr Régis PEFFAULT DE LATOUR
Scientific
Assistance Publique Hopitaux De Paris
研究点 (23)
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