A phase I/II post-cord blood HCT dendritic cell vaccination trial directed against WT1 for pediatric acute myeloid leukemia: the U-DANCE-anti-AML trial

Study design:
This is a single-arm open-label phase I/II intervention study in pediatric AML patients using an ATMP: cord blood-derived dendritic cell (CBDC) vaccine. Data from our historic cohort of pediatric patients with a WT1+ AML and receiving CBT will be used as control group for the primary objective in part B.



Study population:

All pediatric patients with an WT1+ AML and eligible for a CBT as ‘standard of care’ can be included in the current study, taking into account the age limits of the part A of the study (≥12 and ≤17 year of age) . Younger patients will only be included when safe dose has been determined in part A (≥0 - ≤17 year).



Intervention:

CBDC-vaccination (day 0, day 14 and day 28):
Patients will receive three “Full length WT1 encoding” mRNA-electroporated and WT1 15-mer-peptide pool loaded CBDC-vaccinations starting at 8 weeks post-CBT every 2 weeks (hence week 8, 10 and 12). The CBDC vaccine will be split into two equal doses that will be administered intradermally and intravenously.

Cord Derived Dendritic Cell Vaccination directed against WT1 will prevent patients from relapse

In this study, all planned visits (see table 5 for details) are aligned with the “standard of care” SOP-follow-up visits with regard to CBT. As such, no additional visits are needed unless medically required.

Most parameters will be obtained by physical examination or assessed as part of “standard of care” SOP diagnostics. When extra blood is collected for study specific assessments (WT1-specific immunity and WT1 MRD levels) this blood will always be collected in combination with the “standard of care” blood collection. As such, no extra vein punctures will need to be performed.

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 of the CB graft under GMP conditions and cryopreserved in the “Cell Therapy Facility” of the UMC Utrecht.



All pediatric AML patients eligible for allo-HCT according to the international NOPHO AML protocol and the national (DCOG) guidelines, and undergoing a CBT at the pediatric blood and marrow transplantation program of the UMC Utrecht, are eligible for part A and B this study.



Although DC vaccinations have been used in allo-HCT settings, no previous studies have been performed using a CBDC vaccine after CBT. This study will therefore be subdivided into 2 parts: Part A to determine a safe dose of the vaccination and Part B to study its activity measured as the one-year relapse-free survival rate, based on an expansion cohort.



Part A: Safety: Occurrence of DLTs including aGvHD (according to Glucksberg criteria 1) 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 historic controls.



Patients will be vaccinated three times biweekly by combined intradermal and intravenous administration of the WT1 loaded-CBDC vaccine, starting at 8 weeks after CBT.