Phase II Study Testing Prophylaxis Feasibility of Graft Versus Host Disease With Only High Dose Cyclophosphamide Post-transplantation for Patients Eligible to a Reduced-intensity Conditioning Regiment Prior to Allogenic Transplantation With a Compatible Familial or Non-familial Donor.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Incidence of grade 3 and 4 acute GVHD cortico-resistant
研究概览
简要总结
Acute or chronic graft versus host disease is still the major complication of stem cells transplantation regarding morbidity and mortality.
Recently, high dose cyclophosphamide utilization early after post-transplantation (day+ 3 and +4) not only for patients with HLA- haploidentical donor but also for patients with Human Leukocyte Antigen (HLA)-compatible donor, showed a great control of graft versus host disease after transplantation, allowing to consider stopping immunosuppressive treatment after the transplantation (Neoral=cyclosporine, cell-cept=mycophenolate mofetil). Indeed, this step has already been completed in myeloablative transplantation in adult patients.
This approach could enable to avoid in the end several complications related to long term immunosuppressive drugs administration, while promoting quicker immunity recovery.
详细描述
The BALTIMORE conditioning regiment will be used in this study with peripheral stem cell transplantation and fludarabine will be replaced by clofarabine for myeloid diseases (Acute Myeloide Leukemia, Myelodysplasia , myelofibrosis, Chronic Myeoloid Leukemia..) because of better antitumoral activity in this setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •adults ≤ 70 years old
- •indication to stem cells transplantation with reduced-intensity conditioning regimen
- •with a HLA-compatible familial 10/10 or non-familial donor
- •Written signed informed consent form
- •woman with childbearing potential under efficient control birth method during the trial and up to 12 months after cyclophosphamide stop
- •men under efficient control birth method during the trial and up to 6 months after cyclophosphamide stop
- •Negative serology to B and C hepatitis and to HIV
- •Affiliated to social security
排除标准
- •- Eligible to myeloablative contioning regimen
- •Other progressive malignancy disease or history of prior other malignancy in the last two years, with the exception of: curatively treated basal cell carcinoma or carcinoma in situ of the cervix
- •Progressive mental illness disease
- •Pregnant or Breastfeeding woman
- •woman with childbearing potential without any efficient control birth
- •Serious concomitant infection and not controlled
- •Contra-indications to allogenic transplantation, especially:
- •Cardiac: left ventricular ejection fraction <45% assessed by transthoracic echography or isotopic method (isotopic gamma-angiography)
- •Respiratory: DLCO limiting fludarabine and busulfan use (DLCO< 40% of theorical value)
- •Renal: creatinine clearance < 60ml/min (MDRD method)
- •Hepatic: transaminases >5 Uper Per Normal (UPN) or bilirubin> 2 UPN
- •Contra-indications to cyclophosphamide:
- •Urinary tract infections
- •Acute urothelial toxicity due to cytotoxic chemotherapy or to radiotherapy
- •Obstruction of urines flow
- •Pre-existing hemorrhagic cystitis
- •Yellow fever vaccination
- •Cardiac condition preventing high dose cyclophosphamide utilization :
- •New York Heart Association (NYHA) functional class II, III or IV
- •Rhythmic, valvular or ischemic cardiomyopathy
- •Patient under guardianship or curatorship
- •Patient under judicial protection
- •Known or suspected hypersensitivity to cyclophosphamide
- •Known or suspected hypersensitivity to rabbit proteins
研究组 & 干预措施
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
干预措施: Fludarabine (Drug)
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
干预措施: Full body irradiation (Radiation)
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
干预措施: Cyclophosphamide (Drug)
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
干预措施: stem cell transplantation (Other)
LYMPHOID HEMOPATHY without ATG
patients with lymphoid hemopathy
干预措施: nuclear cells (Other)
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
干预措施: Clofarabine (Drug)
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
干预措施: Full body irradiation (Radiation)
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
干预措施: Cyclophosphamide (Drug)
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
干预措施: stem cell transplantation (Other)
MYELOID HEMOPATHY without ATG
patients with myeloid hemopathy
干预措施: nuclear cells (Other)
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Fludarabine (Drug)
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Full body irradiation (Radiation)
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Cyclophosphamide (Drug)
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: stem cell transplantation (Other)
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: nuclear cells (Other)
LYMPHOID HEMOPATHY witH ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Thymoglobulin Injectable Product (Drug)
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Clofarabine (Drug)
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Full body irradiation (Radiation)
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Cyclophosphamide (Drug)
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: stem cell transplantation (Other)
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: nuclear cells (Other)
MYELOID HEMOPATHY with ATG
patients inclued after 14 dec 2020, received a conditionnement regimen with ATG on Day -2 to reduce GVHD GRADE 1-2 incidence
干预措施: Thymoglobulin Injectable Product (Drug)
结局指标
主要结局
Incidence of grade 3 and 4 acute GVHD cortico-resistant
时间窗: 100 days after transplantation
acute GVHD will be evaluated from International Mount Sinai criteria
次要结局
- disease free survival (DFS)(one year, the last follow-up visit)
- Overall survival (OS)(one year, the last follow-up visit)
- Chimerism(1, 2, 3, 6 and 12 months after transplantation)
- graft and relapse free survival(one year)
- Infections frequency(one year)
- Engraftment(one year)
- Identification of ghost factors associated with GVHD(one year)
- non relapse mortality (NRM)(last follow-up visit)
- Immune reconstitution(3, 6 and 12 months after transplantation)
- Adverse events of grade 3 and 4 after transplantation(one year)
- chronic GVHD(one year)
- compare OS between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare grade 2-4 and 3-4 acute GVHD between patients with ATG and patients without ATG(one year)
- compare chronic GVHD between patients with ATG and patients without ATG(one year)
- compare DFS between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare Relapse between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare NRM between patients with ATG and patients without ATG(one year, last follow-up visit)
- compare Infections frequency between patients with ATG and patients without ATG(one year)