Safety and Feasibility of Total Marrow and Total Lymphoid Irradiation as Conditioning Regimen in Allogeneic Hematopoietic Stem-cell Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Early mortality rate
研究概览
简要总结
Multiple conditioning regimens have been used for the HSCT, some of which include radiotherapy. Total body irradiation (TBI) has demonstrated to be superior to chemotherapy alone in the phase III FORUM trial. However, concerns for long-term toxicity have made TBI less used. Total marrow and lymphoid irradiation (TMLI) has emerged as a new alternative that can potentially keep the benefits of radiation but reducing toxicity to healthy tissues.
The primary objective of this trial is to evaluate the feasibility and safety of TMLI as part of conditioning schemes with or without etoposide for HSCT in patients between age 16 and 45 years with ALL in first line or relapsed disease. As secondary endpoint the efficacy will be assessed by minimal residual disease at 60 days post-transplant, as well as other outcome measures such as non-relapse mortality (NRM), relapse free survival (RFS) and overall survival (OS).
详细描述
TMLI will be administered as part of the conventional reduced intensity conditioning scheme of our institution:
Fludarabine 25 mg/m2 + cyclophosphamide 350 mg/m2 on days -6 to -3, for patients with positive measurable residual disease TMLI will be added in doses of 12 Gy on days -3 to -1 divided into 6 fractions of 2 Gy every 12 hours for 3 days, which will be administered through a computed tomography tomotherapy system.
Infusion of peripheral blood hematopoietic stem cells will be performed on day 0 and after this, prophylaxis for GVHD with post-transplant cyclophosphamide 50 mg/kg will be administered on days +3 and +4, followed by tacrolimus or cyclosporine A plus mycophenolate mofetil regardless of HLA matching.
The procedure for the donation of hematopoietic cells will be done through a peripheral blood apheresis with previous stimulation with filgrastim at 10 mcg/kg for 4 days according to the standardized procedures of our institution.
The leukocyte and platelet count will be monitored by serial complete blood count, and a bone marrow aspiration (BMA) and minimal residual disease (MRD) will be performed on day 60 after transplantation.
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
- 16 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of ALL confirmed by flow cytometry.
- •Patients between age 16 and 45 years with ALL in first remission, refractory, or relapsing
- •Patients who have an identical or haploidentical allogeneic donor by high resolution HLA
排除标准
- •Patients who do not meet the age previously mentioned.
- •Patient with comorbidities that rule them out for HSCT, with a Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) greater than
- •Poor performance status or Karnofsky less than 70%
- •Transthoracic echocardiogram with alteration in myocardial function with left ventricular ejection fraction (LVEF) less than 50%
- •Patients who previously and for another reason have already received radiotherapy or who refuse to receive it
结局指标
主要结局
Early mortality rate
时间窗: 30 days
Primary outcome of safety will be determined by early mortality rate (before day +30) with an expected rate lower than 15%.
Serious adverse events
时间窗: 30 days
Co-primary outcome will be the appearance of serious adverse effects (grade equal to or higher than 3) according to the common terminology criteria for adverse events of the US National Cancer Institute (NCL-CTCAE v.5).
次要结局
- Measurable residual disease(60 days)
- Non-relapse mortality(12 months)
- Event-free survival(12 months)
- Overall survival(12 months)
- Graft versus host disease incidence(12 months)
研究者
David Gomez Almaguer
Head of hematology
Hospital Universitario Dr. Jose E. Gonzalez