Allo-allo Tandem Matched Stem Cell Transplantation (AATT) for the Treatment of Patients With Refractory Acute Leukemia; a Feasibility Phase I/II Study
试验速览
- 阶段
- 1 期
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Transplant-related mortality (TRM) of SCT II.
研究概览
简要总结
Refractory acute leukemia (AL) occurs in a significant percentage of the AL patients and presents a therapeutic challenge. Allogeneic stem cell transplantation (allo-SCT) is the only curative option for these patients. Although many of the patients with refractory AL that undergo myeloablative SCT initially achieve complete remission, most relapse later on, and the long-term disease free survival is poor. In order to achieve better leukemic control, most transplant centers employ post transplant early withdrawal of the anti-GVHD immunosuppression; hence exposing the patients to high risk of GVHD associated morbidity and mortality. This study will try to address this common scenario, namely early and late relapse. The investigators will try to attain better leukemic control by re-inducing the patients, 6 weeks after the 1st transplant with further myeloablative treatment (busulfex and thiotepa) followed by allogeneic stem cell support (transplant II).
详细描述
The effects of feasibility oExperimental design and methods f allo-allo tandem matched stem cell transplantation (AATT) in patients with refractory leukemia will be evaluated in a clinical setting. The current study is limited only for patients with refractory disease that received and failed up to 2 lines of salvage therapy, in good performance status and younger than 50 years old. Only patients that will achieve complete remission after transplant I, will have no major organ dysfunction and with acceptable performance status, will be treated with transplant II. Close monitoring with strict stopping rules including in case of excess transplant related morality, acute or chronic GVHD or graft failure will be employed.
Treatment schedule:
15 patients (divided into 2 cohorts, see below) with matched family member or unrelated donor will be included in single arm open phase I/II trial.
Conditioning protocol:
All patients will be prepared by the same sequential conditioning protocols:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient age 3-50 years old with refractory acute leukemia (primary refractory or refractory relapse I or II) unresponsive to up to 2 salvage lines with a matched donor (related or unrelated, matched defined as 8/8 HLA matching).
- •A donor willing and capable of donating peripheral blood stem cells and preferably also bone marrow cells, and lymphocytes if indicated.
- •Each patient / patient's guardian must sign written informed consent.
- •Patients must have an ECOG PS ≤ 1; Creatinine <1.5 mg/dl; Ejection fraction >45%; DLCO >70% of predicted; Serum bilirubin <2 mg/dl; elevated GPT or GOT < 2 x normal values before transplant I.
排除标准
- •Not fulfilling any of the inclusion criteria.
- •In complete or very good partial remission.
- •Beyond 2nd relapse.
- •Received > 2 lines of salvage therapy.
- •Active CNS involvement of the leukemia
- •Active life-threatening infection.
- •Overt untreated infection.
- •HIV seropositivity, Hepatitis B or C antigen positivity with evidence of active hepatitis.
- •Donor contraindication (HIV seropositive confirmed by Western Blot, Hepatitis B antigenemia, HCV, evidence of bone marrow disease, unable to donate bone marrow or peripheral blood due to concurrent medical condition).
- •Previous autologous or allogeneic stem cell transplantation.
- •Inability to comply with study requirements.
结局指标
主要结局
Transplant-related mortality (TRM) of SCT II.
时间窗: 240d
Transplant-related toxicity (TRT) of SCT II.
时间窗: 240d
次要结局
- GVHD grade following SCT II(240d)
- Day of platelet engraftment >20x109/L at SCT II(240d)
- Day of platelet engraftment >50x109/L at SCT II(240d)
- Acute GVHD occurrence ≥ 2 following SCT II(100d)
- Time to acute GVHD following SCT II(100d)
- Overall survival at 180 days from SCT II(180d)
- Day of neutrophil engraftment at SCT II(240d)
- Disease free survival at 180 days SCT II(180d)
- Infections incidence(240d)
- Immune reconstitution(240d)
研究者
SHAPIRA MICHAEL
Prof shapira
Hadassah Medical Organization