Pilot Study of Co-Infusion of Donor Lymphocytes Enriched With Regulatory T Lymphocytes With Ex-vivo CD3-Depleted Hematopoietic Stem Cell Graft for the Prevention of Graft-versus-Host Disease in Children With Hematopoietic and Lymphoid Tissue Neoplasms
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Feasibility- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Two key methods of GVHD prevention in allogeneic HSCT have a number of limitations: ex vivo T depletion is associated with an excess of infectious complications, and pharmacological immunosuppression with insufficient efficacy of GVHD prevention. Modern graft engineering technologies make it possible to create a graft with a balanced cell composition, reducing the risk of adverse events, in particular, severe forms of acute and chronic GVHD, while preserving the immunological function of the graft. In the proposed concept, enrichment of the T graft with regulatory cells will reduce the risk of GVHD and preserve a sufficient number of T lymphocytes in the graft for the formation of protective anti-infective immunity in the early stages after HSCT. The combination of partial T depletion and pharmacological immunosuppression minimized in volume and duration will combine the advantages of T depletion (early engraftment, low risk of GVHD, low risk of organ complications) and pharmacological prophylaxis (restoration of anti-infective immunity).
详细描述
- Infusion of ex-vivo T-depleted peripheral blood hematopoietic stem cells (CD3 depletion product)
- Infusion of donor lymphocytes enriched with T regulatory lymphocytes (CD25 selective product)
- Drug therapy (pharmacological prophylaxis of GVHD)
- Cyclosporine A
- Sirolimus o Ruxolitinib o Abatacept
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Care Provider)
入排标准
- 年龄范围
- 1 Year 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent signed by the patient (age 14 to 25 years) and/or his/her legal representative (age 0 to 18 years).
- •The patient has an indication for allogeneic hematopoietic stem cell transplantation (HSCT) established in accordance with the current regulatory framework
- •Planned HSCT from a haploidentical donor
- •The Karnofsky or Lansky score is more than 70%
- •Life expectancy of at least 8 weeks
- •Heart function: ejection fraction of at least 40%
- •Consent to continue follow-up for 3 years
排除标准
- •Acute viral hepatitis or acute HIV infection
- •Hypoxemia with SaO2 <90%
- •Bilirubin >3 normal
- •Creatinine >3 norms
- •Pregnancy and lactation
- •Life-threatening infection
- •Severe (>?) pathology of the central nervous system (epilepsy, dementia, organic damage to the central nervous system)
- •Karnofsky score or Lansky score <70%
研究组 & 干预措施
Cyclosporine A
Four groups corresponding to the pharmacological prophylaxis of GVHD: 1) Cyclosporine A
干预措施: Cyclosporine A (CsA) (Drug)
Sirolimus
Drug therapy (pharmacological prophylaxis of GVHD) 2) Sirolimus
干预措施: Sirolimus (Drug)
Ruxolitinib
Drug therapy (pharmacological prophylaxis of GVHD) Ruxolitinib
干预措施: Ruxolitinib (JAKAVI®) (Drug)
Abatacept
Drug therapy (pharmacological prophylaxis of GVHD) Abatacept
干预措施: Abatacept (Drug)
结局指标
主要结局
Feasibility- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: day 30
proportion of patients who received an infusion of the planned dose of regulatory T lymphocytes (at least 80%)
Safety- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: 120 days after HSCT
Cumulative risk of GVHD Grade III-IV (target \< 5%)
次要结局
- Cumulative probability of engraftment(up to 100 day)
- Time to engraftment of neutrophils and platelets(100 day after HSCT)
- Cumulative risk of acute GVHD Grade II-IV(up to 100 days after HSCT)
- Cumulative risk of viral(at 120 day after HSCT)
- cumulative risk of developing severe chronic GVHD(at 2 years)
- Cumulative risk of leukemia relapse(at 2 years)
- Cumulative risk of non-relapse mortality(at 100 days and 2 years)
- Overall survival(at 3 years)
- Event-free survival(at 3 years)
- GVHD- and relapse-free survival(at 3 years)