Phase III Study Comparing GVHD Prophylaxis With ATG-thymoglobulin to ATLG-grafalon in Elderly Patients With Acute Myeloid Leukemia or Myelodysplasic 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
概览
- 阶段
- 3 期
- 干预措施
- Grafalon
- 疾病 / 适应症
- GVHD
- 发起方
- Assistance Publique - Hôpitaux de Paris
- 入组人数
- 324
- 试验地点
- 28
- 主要终点
- Incidence of grade II-IV acute Graft Versus Host Disease (GVHD) according to the Mount Sinai Acute GVHD International Consortium (MAGIC) classification
- 状态
- 招募中
- 最后更新
- 5天前
概览
简要总结
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative therapy in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Most of the patients requiring an allo-HSCT are above 50 years of age and are transplanted with a reduced intensity conditioning (RIC) regimen. The optimal RIC and Graft Versus Host Disease (GVHD) prophylaxis regimen allowing a good control of the disease while preventing GVHD remains to be determined for elderly patients. A phase III trial comparing the conventional RIC fludarabine-busulfan 2 days to fludarabine-treosulfan demonstrated an advantage for the flu-treosulfan arm in terms of event free survival (EFS), that should therefore be considered as the new standard of RIC regimen for AML and MDS. GVHD prevention has a crucial role in post-transplant outcomes by potentially interfering with the graft-versus-leukemia (GVL) effect and immune reconstitution. Anti-thymocyte globulins (ATG) are recommended to reduce the risk of acute and chronic GVHD in transplants performed with matched unrelated donors. However, the optimal type of ATG between the 2 approved brands (ATG-thymoglobulin and ATLG-grafalon) displaying distinct characteristics and the optimal dose of ATG are still unknown. In a retrospective study of patients transplanted mainly with RIC with matched related and unrelated donors for haematological malignancies, Anti-T lymphocyte globulin (ATLG) was associated with a reduction of grade II-IV acute GVHD in comparison to ATG without increasing the incidence of relapse.
This phase III randomised study propose to compare GVHD prevention with ATG versus ATLG in AML and MDS patients above 50 years of age transplanted with a matched unrelated donor following a fludarabine-treosulfan RIC, with the hypothesis that ATLG would better control GVHD in this population of patients thus limiting the risk of morbidity and mortality of the procedure.
研究者
入排标准
入选标准
- •Age ≥ 50 and ≤ 70 years
- •Patient between 50 and 55 years should be unfit for a myeloblative conditioning (SORROR score ≥2)
- •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 \[rapide blast increase, life-threatening neutropenia (\<0.3 G/L) or thrombopenia (\<30G/L) or high transfusion needs (\>2/month for 6 months)\]
- •Without an HLA matched related donor
- •Having an identified matched HLA 10/10 unrelated donor
- •With usual criteria for HSCT:
- •ECOG performans status ≤ 2
- •No severe and uncontrolled infection
- •Cardiac left ventricular ejection fraction ≥50%
- •Lung DLCO \> 40%
排除标准
- •Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix)
- •Uncontrolled infection
- •Seropositivity for HIV or HTLV-1 or active hepatitis B or C
- •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
- •Patients with any debilitating medical or psychiatric illness, which would preclude the realization of the SCT or the understanding of the protocol
研究组 & 干预措施
Anti-T lymphocyte globulin (ATLG)
干预措施: Grafalon
Anti Thymocyte Globulins (ATG)
干预措施: Thymoglobulin
结局指标
主要结局
Incidence of grade II-IV acute Graft Versus Host Disease (GVHD) according to the Mount Sinai Acute GVHD International Consortium (MAGIC) classification
时间窗: At day 100 post-transplantation
Acute GVHD MAGIC classification permit to diagnose and score the severity of acute GVHD. MAGIC score varies from Grade 0 to Grade 4. The higher the score the more severe the damage.
次要结局
- T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood(24 months after transplantation)
- Number of patients with at least 3 consecutive days with neutrophils > 0.5 G/L and platelets > 20 G/L(Up to 24 months)
- Percentage of chimerism(12 months after transplantation)
- Incidence of chronic GVHD(24 months after transplantation)
- Progression free survival(24 months after transplantation)
- Health-related Quality of life(12 months after transplantation)
- Number of severe infections(12 months after transplantation)
- Incidence of CytoMegaloVirus (CMV) reactivation(12 months after transplantation)
- Overall survival(24 months after transplantation)
- Incidence and severity of veino-occlusive disease (VOD)(100 days after transplantation)
- Incidence of grade I acute GVHD(Up to 24 months)
- Incidence of relapse(24 months after transplantation)
- Incidence of Ebstein Barr Virus (EBV) reactivation(12 months after transplantation)
- Non-relapse mortality(24 months after transplantation)
- GVHD and relapse free survival (GRFS)(Up to 24 months after transplantation)
- Lymphocyte counts on standard blood counts before conditioning(7 days before transplantation)
- Number of days of hospitalization for the transplant and after the hospitalization for transplantation related complications(Up to 12 months after transplantation)
- Number of late acute GvHD, overlap syndromes and chronic GvHD(from day 100 to day 120 after transplantation)
- Incidence of Ebstein Barr Virus (EBV) reactivation(100 days after transplantation)
- T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood(1 month after transplantation)
- Incidence of Ebstein Barr Virus (EBV) reactivation(6 months after transplantation)
- Non-relapse mortality(6 months after transplantation)
- Non-relapse mortality(12 months after transplantation)
- Overall survival(12 months after transplantation)
- T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood(100 days after transplantation)
- T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood(6 months after transplantation)
- T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood(12 months after transplantation)
- Percentage of chimerism(1 month after transplantation)
- Percentage of chimerism(100 days after transplantation)
- Percentage of chimerism(6 months after transplantation)
- Incidence of chronic GVHD(12 months after transplantation)
- Incidence of relapse(12 months after transplantation)
- Progression free survival(12 months after transplantation)
- Number of severe infections(100 days after transplantation)
- Incidence of CytoMegaloVirus (CMV) reactivation(100 days after transplantation)
- Incidence of CytoMegaloVirus (CMV) reactivation(6 months after transplantation)
- Health-related Quality of life(At inclusion)
- Health-related Quality of life(100 days after transplantation)
- Health-related Quality of life(6 months after transplantation)