A phase I/II post-cord blood HCT dendritic cell vaccination trial directed against WT1 for pediatric and young adult acute myeloid leukemia: the U-DANCE-anti-AML trial.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Part A: Safety: Occurrence of DLTs from the first vaccination (t=0) until 84 days after the third CBDC vaccination. The 6 patients receiving dose that is considered safe will also be included in first stage of the 2-stage phase 2 design.
研究概览
简要总结
The primary objective of Part A is to assess the safe dose for CBDC vaccination after CBT, defined by the occurrence of dose limiting toxicities (DLTs). The DLT evaluation period lasts from the first vaccination until 84 days after the third CBDC vaccination. The primary objective of Part B is to demonstrate an increase of 20% ( from 50% to 70%) in the WT1+ AML relapse-free survival rate using a WT1-loaded CBDC vaccine, at one year after the first vaccination. A historic cohort (2010-2015) from patients who received a CBT but not a CBDC vaccination was used as reference data for the Simon-2-stage design.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •AML patients eligible for allo-HCT according to standard-of-care guidelines, with overexpression of WT1 mRNA in an AML sample (>50 copies WT1/10^4 copies ABL for PB, and >250 copies WT1/10^4 copies ABL for BM) 1 taken at diagnosis and/or relapse after (re-)induction chemotherapy.
- •Indication for CB-HCT according to the Transplant Center guidelines.
- •CB selection criteria: the 80% fraction of the unit should contain a minimum total nucleated cell number of 3x10^7 NC/Kg criteria for any match grade (before cryo-preservation). Preferable CD34+/Kg dose: > 1x10e5 in the 80%.
- •The whole CB unit should contain more than 7.5x10^6 total CD34+ before freeze.
- •Karnofsky/Lansky score ≥
- •Age limits for part A ≥12 and ≤30 years of age (first three patients ≥16 years of age) for part B: 0 and ≤30 years of age.
- •Signed informed consent.
排除标准
- •Patients who are pregnant or breast-feeding or unwilling to use adequate contraceptive methods.
- •Known allergies to compounds used in the CBDC production process or the local anesthetic “lidocaine-tetracaine (Rapydan®) and EMLA® (lidocaine/ prilocaine) plasters
- •Patients included in other intervention studies influencing the endpoints of this study.
- •No signed informed consent.
结局指标
主要结局
Part A: Safety: Occurrence of DLTs from the first vaccination (t=0) until 84 days after the third CBDC vaccination. The 6 patients receiving dose that is considered safe will also be included in first stage of the 2-stage phase 2 design.
Part A: Safety: Occurrence of DLTs from the first vaccination (t=0) until 84 days after the third CBDC vaccination. The 6 patients receiving dose that is considered safe will also be included in first stage of the 2-stage phase 2 design.
Part B: Activity: One-year WT1+ AML relapse-free survival rate from the time of the first vaccination as compared to historic controls.
Part B: Activity: One-year WT1+ AML relapse-free survival rate from the time of the first vaccination as compared to historic controls.
次要结局
- Part A + B: One-year cumulative incidence of cGvHD (according to NIH criteria91) from the first vaccination until one year of follow-up.
- Part A + B: One-year overall survival rate from the time of first vaccination.
- Part A + B: One-year WT1+AML relapse-free survival rate, from the time of first vaccination.
- 4. Part A+B: One-year cumulative increase of WT1-specific immunity defined by In vitro T cell reactivity towards MHC class I and II-restricted WT1 epitopes by multiplex-cytokine assay and FACS of CD8/CD137 and CD4/CD154 expression by PBMCs stimulation with WT1 peptivator. Quantitative and qualitative FACS analysis of WT1-specific-positive CD8+ T cells using HLA-A2 multimers against a wide range of possible WT1 peptides.
研究者
C.A. Lindemans
Scientific
Prinses Maxima Centrum voor Kinderoncologie B.V.