Pediatric AML patient elegible for allogeneic hematopoietic cell transplantation
Conditions
Interventions
CBDC vaccine.
This advanced therapy medicinal product (ATMP) is a full-length WT1-mRNA electroporated and WT1 peptide pool-loaded CBDC vaccine produced from CD34+ cells isolated from the 20% fraction
Sponsors
University Medical Center Utrecht,
The Netherlands
UMC Utrecht
Eligibility
Inclusion criteria
Inclusion criteria: •Pediatric 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 52 taken at diagnosis and/or relapse after (re-)induction chemotherapy. •Indication for CB-HCT according to the UMC Utrecht 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% fraction •The whole CB unit should contain more than 7.5x10^6 total CD34+ before freeze. •Karnofsky/Lansky score ≥70 •Age limits for part A (safety run) only: ≥12 and ≤17 years of age, and <18 years for part B of the study. •Signed informed consent
Exclusion criteria
Exclusion criteria: •Patients undergoing allo-HCT with stem cells derived from PBMCs or BM •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 anaestetic “lidocaine-tetracaine (Rapydan®) plasters •Patients included in other intervention studies influencing the endpoints of this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoints: Part A, Safety: Occurrence of DLTs including aGvHD (according to Glucksberg criteria1) from the first vaccination (t=0) until 84 days after the third CBDC vaccination. Part B, Activity: One-year WT1+ AML relapse-free survival rate from the time of the first vaccination as compared to historical controls. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints (part A): - One-year cumulative incidence of WT1-specific immunity after the first vaccination. - One-year overall survival rate, from the time of first vaccination - One-year WT1+AML relapse-free survival rate, from the time of first vaccination. - One-year cumulative incidence of cGvHD (according to NIH criteria2) from the first vaccination. Secondary endpoints (part B): - One-year cumulative incidence of WT1-specific immunity after the first vaccination. - One-year cumulative incidence of cGvHD (according to NIH criteria2) from the first vaccination. - One-year overall survival rate from the time of first vaccination. Exploratory endpoints (part B): - Changes in general immune parameters between those samples taken before and those taken after the first vaccination until one year of follow-up. - Expression of inhibitory (immune checkpoint) molecules on the AML in the case of relapse occurring after the first vaccination until one year of follow-up | — |
Contacts
Public ContactJ.J. Boelens
room KC.03.065.2
Outcome results
None listed