Feasibility and Efficacy of Modified Donor Lymphocytes Infusion (CD45RA Negative Selected) After Haploidentical Transplantation With Post-transplantation Cyclophosphamide in Patients With Hematological Malignancies (ONC-2016-002).
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- to evaluate the efficacy of CD45RA-depleted haplo-DLIs (mDLIs) in the setting of patients receiving haplo-HSCT and PT-Cy, in terms of incidence of viral infections in the post-transplant period
研究概览
简要总结
Interventional non-randomized trial. The duration of study will be 47 months.
After haploidentical transplantation, patients without complications, mainly a GVHD ≥ grade 2, will receive mDLI. mDLI consists of donor lymphocytes infusion, harvested by apheresis the day before the day planned for infusion (or up to -7 days) as outpatient basis in the Day Hospital using a cell separator.
The mDLIs preparation will be performed using a CliniMACS® (Miltenyi). A CD45RA-depletion Product LineTM from Miltenyi, including disposable reagents and devices, will be used.
The planned number of mDLI is 3.
- Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.
- 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.
- 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient. Day +50 was chosen as the starting time-point because at that time over two thirds of all acute GvHD episodes have already occurred in the absence of DLI (internal data, median +49 after bone marrow, +27 after peripheral stem cells); acute GvHD will thus be less likely a confounding factor. The choice of a maximum number of 3 mDLIs is based on the relatively narrow time interval where outcome improvement is expected, that is mainly in the first 6 months after haplo-HSCT. The planned doses are those mainly used in conventional DLIs during haplo-HSCT setting.
Stopping infusion rules:
If GvHD ≥ Grade 2 or relapse occurs, mDLIs will not be administered at any time and patient will be permanently discontinued from treatment.
If any severe adverse event (SAE) occurs after the first mDLI, the administration of mDLI will be interrupted for a maximum of 6 weeks until event resolution. If the SAE does not resolve after 6 weeks from last mDLI infusion, patient will be permanently discontinued. At any time, the experimental treatment may be stopped according to clinical judgement or patient's willing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written, signed informed consent;
- •Adult patients aged ≥18 years;
- •Patients who underwent haploidentical transplantation with PT-Cy for haematological diseases since no more than 56 days;
- •Patient who received myeloablative conditioning regimen, reduced intensity conditioning regimens, or non-myeloablative conditioning regimens;
- •Availability of haploidentical donor (defined as those with ≥ 2 differences within one HLA haplotype) who agree to donate peripheral blood cells by leukapheresis and able to donate the day before the day planned for infusion (or up to - 7 days);
- •GVHD/HVG prophylaxis consists in Cyclophosphamide: 50 mg/kg/day, day +3 and +4, Cyclosporine A: 3 mg/kg/day from day +5 to day +100, with tapering in 2 months Mycophenolate mofetil: 45 mg/kg/day, from day +5 to day +35.
排除标准
- •Presence of grade 2-4 acute GVHD;
- •Uncontrolled bacterial, viral or fungal infection;
- •Aplasia defined as ANC less than 500/L;
- •Evidence of disease progression after transplantation;
- •Current participation in another clinical study.
结局指标
主要结局
to evaluate the efficacy of CD45RA-depleted haplo-DLIs (mDLIs) in the setting of patients receiving haplo-HSCT and PT-Cy, in terms of incidence of viral infections in the post-transplant period
时间窗: 100 days
The primary endpoint is the rate of viral infections at day +100 after haplo-BMT.
to evaluate the impact of the modified DLIs on relapse (graft-versus-tumor effect)
时间窗: 1 year
relapse rate
to evaluate the impact of the modified DLIs on the occurrence of GvHD
时间窗: 1 year
acute and chronic GvHD incidence
to evaluate the impact of the modified DLIs on other types of infections;
时间窗: 100 days
100-day cumulative incidence of other type of infections
次要结局
未报告次要终点