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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Prinses Maxima Centrum voor Kinderoncologie B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

6 Dec 2023 → ongoing

Decision date (initial)

2024-11-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-517922-24-00

EudraCT number

2018-000698-54

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Dose response, Therapy

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.

Secondary objectives 8

1. Part A: To assess the induction/increase of WT1-specific immunity in vaccinated individuals before vaccination, at 1 month, 6 months and at one year after the first vaccination
2. Part A: To assess overall survival at one year after the first vaccination.
3. Part A: To assess WT1+ AML relapse-free survival at one year after the first vaccination.
4. Part A: Rejection incidence at 1 year.
5. Part B: To assess the induction/increase of WT1-specific immunity in vaccinated individuals before vaccination and during one year of follow-up from the first vaccination.
6. Part B: To assess the safety and tolerability of the vaccination strategy.
7. Part B: To assess the overall survival at one year after the 1st vaccination.
8. Part B: Rejection incidence at 1 year.

Conditions and MedDRA coding

AML: Acute Myeloid Leukemia/ cancer of blood and bone marrow

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 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.
2. Indication for CB-HCT according to the Transplant Center guidelines.
3. 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%.
4. The whole CB unit should contain more than 7.5x10^6 total CD34+ before freeze.
5. Karnofsky/Lansky score ≥70.
6. 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.
7. Signed informed consent.

Exclusion criteria 4

1. Patients who are pregnant or breast-feeding or unwilling to use adequate contraceptive methods.
2. Known allergies to compounds used in the CBDC production process or the local anesthetic “lidocaine-tetracaine (Rapydan®) and EMLA® (lidocaine/ prilocaine) plasters
3. Patients included in other intervention studies influencing the endpoints of this study.
4. No signed informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. Part B: Activity: One-year WT1+ AML relapse-free survival rate from the time of the first vaccination as compared to historic controls.

Secondary endpoints 4

1. Part A + B: One-year cumulative incidence of cGvHD (according to NIH criteria91) from the first vaccination until one year of follow-up.
2. Part A + B: One-year overall survival rate from the time of first vaccination.
3. Part A + B: One-year WT1+AML relapse-free survival rate, from the time of first vaccination.
4. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Prinses Maxima Centrum voor Kinderoncologie B.V.

Sponsor organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Address

Heidelberglaan 25

City

Utrecht

Postcode

3584 CS

Country

Netherlands

Scientific contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

C.A. Lindemans

Public contact point

Organisation

Prinses Maxima Centrum voor Kinderoncologie B.V.

Contact name

TDC Secretary

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications