Clinical Trials Register

Summary
EudraCT Number:	2018-000698-54
Sponsor's Protocol Code Number:	10002
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-05-18
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2018-000698-54

A.3

Full title of the trial

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

Een fase I/II onderzoek naar dendritische celvaccinatie tegen WT1 na een
navelstrengbloed stamceltransplantatie in kinderen en jongvolwassenen met Acute Myeloide
Leukemie: het U-DANCE-tegen-AMLonderzoek

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

U-DANCE-anti-AML

U-DANCE-tegen-AML

A.3.2

Name or abbreviated title of the trial where available

U-DANCE-anti-AML

U-DANCE-tegen-AML

A.4.1

Sponsor's protocol code number

10002

A.5.4

Other Identifiers

Name:

Dutch Compentent authority

Number:

NL65115.000.18

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Prinses Maxima Centrum voor kinderoncologie
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	NWO (ZonMW), KiKa
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Prinses Maxima Centrum
B.5.2	Functional name of contact point	C.A. Lindemans
B.5.3	Address:
B.5.3.1	Street Address	Heidelberglaan 25
B.5.3.2	Town/ city	Utrecht
B.5.3.3	Post code	3584 CT
B.5.3.4	Country	Netherlands
B.5.6	E-mail	c.a.lindemans@prinsesmaximacentrum.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	WT1-loaded CBDC vaccine
D.3.4	Pharmaceutical form	Concentrate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intradermal use Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	WT1 loaded cord blood-derived dendritic cell (CBDC) vaccine
D.3.9.3	Other descriptive name	Cord blood CD34+ stem cell derived and WT1-peptide pool loaded dendritic cell vaccine
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1 to 5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

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

AML: Acute Myeloide Leukemie/ kanker van het bloed en beenmerg

E.1.1.1

Medical condition in easily understood language

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

AML: Acute Myeloide Leukemie/ kanker van het bloed en beenmerg

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10000886
E.1.2	Term	Acute myeloid leukemia
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

- 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 primary objective:
- To assess the safe dose for CBDC vaccination after CBT defined using the occurrence of dose limiting toxicities (DLTs).
The DLT evaluation period lasts from the first vaccination, until 84 days after
the third CBDC vaccination.
Part B primary objective:
- To demonstrate an increase in the WT1+ AML relapse-free survival rate using a WT1-loaded CBDC vaccine, at one year after
the first vaccination (using a historic cohort not receiving a CBDC vaccination as reference data for the Simon-2-stage design).

E.2.2

Secondary objectives of the trial

Part A secondary objectives:
- To assess the safety and tolerability of the vaccination strategy
- To assess the induction/increase of WT1-specific immunity in vaccinated individuals during one year of follow-up from the first
vaccination
- To assess overall survival at one year after the first vaccination
- To assess WT1+ AML relapse-free survival at one year after the first vaccination
Part B: secondary objectives:
- To assess the safety and tolerability of the vaccination strategy
- To assess the induction/increase of WT1-specific immunity in vaccinated individuals during one year of follow-up from the first
vaccination
- To assess overall survival at one year after the first vaccination

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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) taken at diagnosis and/or relapse (re-)induction chemotherapy.
- indication for CB-HCT according to the Prinses Maxima Centrum / UMC Utrecht guidelines
- CB selection criteria: the 80% fraction of the unit should contain a minimum total nucleatd 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 - ≤30 years of age (first 3 patients ≥16 years of age), part B 0- ≤30 years of age

Patienten met AML die in aanmerking komen voor een allogene stamceltransplantatie volgens standaard zorg richtlijnen, met een over-expressie van WT1 mRNA in aan AML monster (>50 kopieen WT1/10^4 kopieen ABL voor perifeer bloed en >250 kopieen WT1/10^4 kopieen ABL voor beenmerg) afgenomen bij de diagnose en/of relapse na inductie of consolidatie chemotherapie
-Indicatie voor navelstreng-allogene stamceltransplantatie volgens UMC Utrecht richtlijnen
-Navelstrengbloed selectiecriteria: de 80% fractie van de unit moet een minimaal aantal kernhoudende cellen bevatten: 3x10^7 NC/Kg Criterium voor iedere match (voor invriezen). Bij voorkeur is de CD34+/kg dosis >1x10e5/Kg in de 80% fractie.
-De totale navelstrengbloed unit moet meer dan 7.5x10^6 total CD34 bevatten + voor invriezen
-Karnofsky/Lansky score ≥70
-Leeftijdsgrenzen voor deel A (veiligheid): ≥12 - ≤30 jaar (eerste drie patiënten 16 jaar en ouder), 0- ≤30 jaar voor deel B

E.4

Principal exclusion criteria

-Patients who are preganant or breast-feeding or unwilling to use adequate contraceptive methods
-Known allergies to compound used in the CBDC production process or the local anesthetic lidocaïne-tetracain (Rapydan®) plasters
-Patients included in other intervention studies influencing the endpoints of this study

Patiënten die zwanger zijn of borstvoeding geven of geen adequate anticonceptie willen gebruiken
- Bekende allergieën voor bestanddelen die gebruikt zijn tijdens het CBDC (uit navelstreng verkregen dendritische cellen) productieproces of voor lokale anaesthesia Lidocaïne-tetracaine (Rapydan®) pleisters
- Patiënten die geïncludeerd zijn in andere interventie studie die de eindpunten van deze studie kunnen beïnvloeden.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoints:

Part A: Safety: Occurrence of DLTs 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.

Deel A: Veiligheid: Frequentie van DLTs vanaf de eerste vaccinatie (t = 0) tot 84 dagen na de derde CBDC vaccinatie
Deel B: Activiteit: Een jaar WT1+ AML recidief-vrije overleving vanaf de 1e vaccinatie, vergeleken met historische controles.

E.5.1.1

Timepoint(s) of evaluation of this end point

part A 84 days after vaccination
part B 1 year after vaccination

deel A 84 dagen na vaccinatie
deel B 1 jaar na vaccinatie

E.5.2

Secondary end point(s)

Secondary endpoints (part A):
- Treatment emergent adverse events (TEAEs), those with initial onset or increasing in severity after the first vaccination.
- 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.
Secondary endpoints (part B):
TEAEs, those with initial onset or increasing in severity after the first vaccination.
- One-year cumulative incidence of WT1-specific immunity after 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

De secundaire eindpunten (deel A)
-Door behandeling ontstane ongewenste voorvallen (TEAEs), vanaf het begin of toegenomen in ernst na de 1e vaccinatie
-Een jaar cumulatieve incidentie van WT1-specifieke immunitiet na de 1e vaccinatie
-Een jaars algehele overleving, vanaf de 1e vaccinatie
-Een jaars WT1 + AML relapse-vrije overleving, vanaf de 1e vaccinatie

De secundaire eindpunten (deel B):
- TEAEs, vanaf het begin of toegenomen in ernst na de 1e vaccinatie
- Een jaar cumulatieve incidentie van WT1-specifieke immunitiet na de 1e vaccinatie
- Een jaar algehele overleving van de eerste vaccinatie
De verkennende eindpunten (deel B):
- Wijzigingen van de algemene immuun parameters tussen de monsters die genomen zijn vóór en degenen die genomen zijn na
de eerste vaccinatie zijn tot één jaar follow-up.
- Expressie van remmende (immuun checkpoint) moleculen op de AML in het geval van recidief die zich voordoet na de eerste
vaccinatie tot één jaar follow-up

E.5.2.1

Timepoint(s) of evaluation of this end point

one year after vaccination

1 jaar na vaccinatie

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

historic cohort of 17 AML patients (transplanted between 2010-2015)

historisch cohort van 17 AML patienten (getransplanteerd tussen 2010-

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

laatste patiënt laatste visite

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard of care according to HCT procedure

standaard zorg volgens de HCT procedure

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-11-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-11-28

P. End of Trial
P.	End of Trial Status	Ongoing

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