Clinical Trials Register

Summary
EudraCT Number:	2014-005123-27
Sponsor's Protocol Code Number:	IRST172.04
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2017-12-15
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-005123-27

A.3

Full title of the trial

Complementary vaccination with dendritic cells pulsed with autologous tumor lysate in resected stage III and IV melanoma patients: a phase II randomized trial (ACDC adjuvant Trial)

A.3.1

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

Complementary vaccination with dendritic cells pulsed with autologous tumor lysate in resected stage III and IV melanoma patients: a phase II randomized trial (ACDC adjuvant Trial)

Vaccinazione complementare con cellule
dendritiche autologhe caricate con lisato od omogenato tumorale autologo dopo chirurgia radicale per metastasi da melanoma in
stadio IV o III metacrono: studio randomizzato di fase II.

A.3.2

Name or abbreviated title of the trial where available

ACDC adjuvant Trial

A.4.1

Sponsor's protocol code number

IRST172.04

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	ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI (IRST) S.R.L. IRCCS
B.1.3.4	Country	Italy
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	IRST IRCCS
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	IRST IRCCS
B.5.2	Functional name of contact point	Centro di Coordinamento Studi IRST
B.5.3	Address:
B.5.3.1	Street Address	Dipartimento di Oncologia ed Ematologia, Ospedale Civile S. Maria delle Croci, viale Randi, 5
B.5.3.2	Town/ city	Ravenna
B.5.3.3	Post code	48121
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390544285813
B.5.5	Fax number	+390544285330
B.5.6	E-mail	cc.ubsc@irst.emr.it

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	DC-VACCINE_IRSTIRCCS
D.3.2	Product code	DC-VACCINE_IRSTIRCCS
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DC-VACCINE_IRSTIRCCS
D.3.9.2	Current sponsor code	DC-VACCINE_IRSTIRCCS
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	7000000 to 14000000
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)	Yes
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.IMP: 2
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	Yes
D.2.1.1.1	Trade name	PROLEUKIN - 18.000.000 UI POLVERE PER SOLUZIONE INIETTABILE O PER INFUSIONE 10 FLACONCINI IN VETRO DA 22.000.000 UI
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	IL2_IRSTIRCCS
D.3.2	Product code	IL2_IRSTIRCCS
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALDESLEUKIN
D.3.9.1	CAS number	110942-02-4
D.3.9.2	Current sponsor code	IL2_IRSTIRCCS
D.3.9.4	EV Substance Code	SUB05303MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3000000
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)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
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

resected stage III and IV melanoma

melanoma stadio III e stadio IV resecato

E.1.1.1

Medical condition in easily understood language

stage III and IV melanoma resected after radical surgery for metastases

melanoma stadio III e stadio IV dopo chirurgia radicale
per metastasi

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10025671
E.1.2	Term	Malignant melanoma stage IV
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10025670
E.1.2	Term	Malignant melanoma stage III
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

RFS: relapse free survival is the time from the
date of randomization to the date of first relapse or the date of death from any cause or the date of the last restaging in non relapsed patients.

RFS: sopravvivenza libera da recidiva; intesa come il periodo tra la data di randomizzazione e la data
della prima recidiva o la data di morte per qualsiasi causa o la data dell'ultima ristadiazione in pazienti senza recidiva.

E.2.2

Secondary objectives of the trial

- OS: Overall survival will be measured from the date of randomization until the date of death from any cause or the last date on which it was known that the patient was alive.
-In vivo and in vitro immunomonitoring.
Immunologic efficacy will be measured by best DTH score (reactivity to lysate or KLH) obtained after at least 4 vaccine doses, alone or combined with IFN-g ELISPOT analysis of tumor antigen-specific circulating effectors obtained after a minimum of 4 vaccine doses, both compared with prevaccine samples. In vivo monitoring will focus on functional phenotyping of circulating immune effectors/regulators, functional characterization of circulating tumor antigen-specific immune effectors and regulators, and identification of serum markers that are predictive of response.
-Toxicity
-Prognostic and predictive marker response
-Immunologic response

- OS: la sopravvivenza globale sarà misurata dalla data di randomizzazione fino alla data di morte per
qualsiasi causa o l'ultima data in cui si sapeva che il paziente era vivo.
- Immunomonitoring In vivo ed in vitro .
L'efficacia immunologica sarà misurata mediante il punteggio migliore al DTH (reattività al lisato o al KLH) ottenuto dopo almeno 4 dosi di vaccino, da solo o in combinazione con l'analisi IFN-g ELISPOT di effettori tumorali circolanti antigeni-specifici ottenuti dopo un minimo di 4 dosi di vaccino, entrambi comparati con campioni pre-vaccino. Il monitoraggio in vivo si concentrerà sulla
fenotipizzazione funzionale degli effettori/regolatori immunitari circolanti, sulla loro caratterizzazione funzionale e sull'identificazione di marcatori sierici che predittivi di risposta.
- Tossicità
- Marcatori di risposta prognostici e predittivi
- Risposta immunologica

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Signed Written Informed Consent: patients must be willing and able to give written informed consent, that have to be given before starting of screening procedure.
2.Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the “Product Specification File”.
3.Patients must have histologically or cytologically confirmed melanoma (all type of melanomas);
4.Patients must be disease free after surgical removal of a metastatic lesions (stage IV or metacronouse stage III)
5.ECOG performance status 0-1
6.Negative screening tests for HIV, HBV HCV and syphilis not older than 30 days before performing any of the GMP-regulated activities required (leukapheresis, collection of tumor biopsies to be used for tumor lysate/homogenate preparation);
7.Men and women aged ≥ 18 years.
8.Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up 8 weeks after the study, in order to minimize the risk of pregnancy;
9.Patients must have normal organ and marrow function according to clinical practice.

1. Firma del consenso informato: i pazienti devono essere disposti e capaci a fornire il proprio consenso informato scritto prima di ogni altra procedura di screening prevista per lo studio.
2. Disponibilità di materiale tumorale raccolto e conservato secondo le procedure del Laboratorio di Terapia Cellulare Somatica IRST.
3. Diagnosi istologica o citologica confermata di melanoma.
4. I pazienti dovranno essere liberi da malattia dopo la chirurgia di rimozione della/e lesioni metastatiche (stadi IV o III metacroni)
5. ECOG performance status 0-1
6. Test per HIV, HBV HCV e sifilide negativi, eseguiti entro 30 giorni dell’esecuzione di qualunque procedura GCP.
7. Uomini e donne di età superiore o uguale a 18 anni.
8. Le donne fertili dovranno utilizzare un adeguato metodo contraccettivo per evitare gravidanze durante lo studio e per le successive 8 settimane.
9. Normale funzionalità midollare e d’organo.

E.4

Principal exclusion criteria

1.Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing must be performed within 30 days before any GMP-regulated activity (leukapheresis and collection of tumor biopsies to be used for tumor lysate preparation).
2.Patients who have had prior lines of systemic chemotherapy, immunotherapy or biological therapy for metastatic melanoma.
3.Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
4.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements (on physician’s judgment).
5.Other known malignant neoplastic diseases in the patient’s medical history with a disease-free interval of less than 3 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
6.Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral anticoagulant therapy) or to undergo surgery.

1. I pazienti che hanno test positivi per HCV, HBV, HIV, o sifilide (test su sangue specifico che devono essere effettuati entro 30 giorni prima di qualsiasi attività regolamentata da GMP (leucaferesi e la raccolta di biopsie tumorali da utilizzare per la preparazione del tumore lisato).
2. I pazienti che hanno ricevuto precedenti linee di chemioterapia sistemica, immunoterapia o terapia biologica per il melanoma metastatico.
3. Partecipazione ad un altro studio clinico con eventuali farmaci sperimentali nei 30 giorni precedenti allo screening dello studio.
4. Malattia non controllata intercorrente tra cui, ma non solo, infezione in corso o attiva, insufficienza cardiaca congestizia sintomatica, angina pectoris instabile, aritmia cardiaca o malattia psichiatrica / situazioni sociali che limiterebbero la conformità con i requisiti di studio (a giudizio del medico).
5. Altre note patologie neoplastiche maligne nella storia clinica del paziente, con un intervallo libero da malattia di meno di 3 anni (tranne per il carcinoma a cellule basali trattato in precedenza e carcinoma in situ della cervice uterina);
6. Qualsiasi controindicazione a sottoporsi a leucaferesi valutata dal transfusionista (ad esempio una grave anemia, piastrinopenia, terapia anticoagulante orale) o a sottoporsi ad un intervento chirurgico.

E.5 End points

E.5.1

Primary end point(s)

RFS: relapse free survival is the time from the date of randomization to the date of first relapse or the date of death from any cause or the date of the last restaging in non relapsed patients.

End point "primario": RFS: sopravvivenza libera da recidiva; intesa come il periodo tra la data di randomizzazione e la data della prima recidiva o la data di morte per qualsiasi causa o la data dell'ultima ristadiazione in pazienti senza recidiva.

E.5.1.1

Timepoint(s) of evaluation of this end point

36 months

36 mesi

E.5.2

Secondary end point(s)

-Immunologic response

- Risposta immunologica

E.5.2.1

Timepoint(s) of evaluation of this end point

36 months

36 mesi

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)

E.7.1.1

First administration to humans

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

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

osservazione (follow-up)

observation (follow-up)

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.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

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

Information not present in EudraCT

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

Information not present in EudraCT

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.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

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)

Yes

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

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

120

F.4.2

For a multinational trial

F.4.2.1

In the EEA

120

F.4.2.2

In the whole clinical trial

120

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)

Patients who relapsed will be contacted by telephone call (or site visit) every 3 months to evaluate survival and to obtain information regarding current anti-cancer regimens and AEs (AEs collected up to 90 days after the end of treatment visit for patient in treatment arm, and up to relapse or maximum 9 months for patients in follow-up arm.) until death or patient becomes lost-to-follow-up.

I pazienti che hanno mostrato recidive saranno contattati tramite telefonata (o visita presso il centro sperimentale) ogni 3 mesi per valutare la sopravvivenza ed ottenere l'indicazione sugli attuali regimi anti-cancro e gli eventi avversi seri (AES, raccolti fino a 90 giorni dopo la visita di fine trattamento per i pazienti assegnati al braccio di terapia, e fino alla ricaduta o al massimo 9 mesi per i pazienti nel braccio di follow-up), fino alla morte o alla perdita al follow-up del paziente.

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

2015-08-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-30

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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