Clinical Trials Register

Summary
EudraCT Number:	2020-002297-26
Sponsor's Protocol Code Number:	NCT04476199
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-25
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-002297-26

A.3

Full title of the trial

Phase II study on Venetoclax (VEN) plus Decitabine (DEC) (VEN-DEC) for elderly (=60 <75years) patients with newly diagnosed Acute Myeloid Leukemia (AML) elegible for allogeneic Stem Cell Transplantation (allo-SCT)

Studio di Fase II su Venetoclax (VEN) e Decitabine (DEC) (VEN-DEC) per pazienti anziani (=60 - <75 anni) con Leucemia Acuta Mieloide di nuova diagnosi (LAM) eleggibili per Trapianto Allogenico di Cellule Staminali Emopoietiche (allo-SCT)

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

VEN-DEC GITMO Study

A.4.1

Sponsor's protocol code number

NCT04476199

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	GITMO GRUPPO ITALIANO PER IL TRAPIANTO DI MIDOLLO OSSEO, CELLULE STAMINALI EMOPOIETICHE E TERAPIA
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	Abbvie
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Janssen
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	Il GITMO “Gruppo Italiano per il Trapianto di Midollo Osseo, cellule staminali emopoietiche e terapia cellulare
B.5.2	Functional name of contact point	Trial Office
B.5.3	Address:
B.5.3.1	Street Address	Largo R. Benzi 10
B.5.3.2	Town/ city	Genova
B.5.3.3	Post code	16132
B.5.3.4	Country	Italy
B.5.4	Telephone number	0226436293
B.5.5	Fax number	00000000000
B.5.6	E-mail	Segreteria.presidenza@gitmo.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	Yes
D.2.1.1.1	Trade name	Venclyxto
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbvie
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	Venclyxto
D.3.2	Product code	[ABT-199]
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.2	Current sponsor code	ABT-199
D.3.9.3	Other descriptive name	Venetoclax 10 mg
D.3.9.4	EV Substance Code	SUB176260
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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)	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)	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.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	DACOGEN
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	DACOGEN
D.3.2	Product code	[DACOGEN]
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	2353-33-5
D.3.9.2	Current sponsor code	DACOGEN
D.3.9.3	Other descriptive name	DECITABINA
D.3.9.4	EV Substance Code	SUB06932MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
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)	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)	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

allogeneic transplantation in CR / Cri / MLFS condition

trapianto allogenico in condizione di CR/Cri/MLFS

E.1.1.1

Medical condition in easily understood language

allogeneic transplantation in CR / Cri / MLFS condition

trapianto allogenico in condizione di CR/Cri/MLFS

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10000880
E.1.2	Term	Acute myeloid leukaemia
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

Evaluate the number of elderly patients (aged> 60 - <75 years) with LAM, eligible for allo-SCT, treated with the "chemo-free" VEN-DEC combination undergoing
pat.

Valutare il numero di pazienti anziani (età >60 - <75 anni) con LAM, eleggibili ad allo-SCT, trattati con la combinazione “chemo-free” VEN-DEC sottoposti a ologia
pat.

E.2.2

Secondary objectives of the trial

incidence and severity of adverse drug reactions (ADR), classified according to SOC (System Organ Class) and preferred term (PT) from the start of treatment with VEN-DEC to trans Evaluation, of the efficacy of the therapy with VEN-DEC, Evaluation of the outcome of the transplant in terms of: 1) incidence of graft failure per day +30, +100 from the transplant 2) incidence of non-relapse mortality (NRM) per day + 100, 1 year and 2 years after transplantation3) acute GVHD incidence and severity at +100 after transplantation4) chronic GVHD incidence and severity 1 year and 2 years after transplantation5) probability of GRFS (Graft-free relapse free survival) a 1 year and 2 years after transplantation - Relapse incidence (RI) at 1 year and 2 years after trans - Overall survival (OS) at 1 year and 2 years after trans Disease free survival (DFS) at 1 year and 2 years after transpl immunophenotypic, cytogenetic, molecular and genomic profile from NGS with sensitivity (CR / Cri / MLFS)

incidenza e severità delle reazioni avverse ai farmaci (ADR), classificati secondo SOC (System Organ Class) and preferred term (PT) dall’inizio del trattamento con VEN-DEC al trapianto
Valutazio, ne dell’efficacia della terapia con VEN-DEC, Valutazione dell’outcome del trapianto in termini di:1) incidenza di graft failure al giorno +30 , +100 dal trapianto2) incidenza di non relapse mortality (NRM) al giorno +100, a 1 anno e a 2 anni dal trapianto3) incidenza e severità di GVHD acuta a +100 dal trapianto4) incidenza e severità di GVHD cronica a 1 anno e 2 anni dal trapianto5) probabilità di GRFS (Graft-free relapse free survival) a 1 anno e 2 anni dal trapianto- Incidenza di ricaduta (RI) a 1 anno e 2 anni dal trapianto- Overall survival (OS) a 1 anno e 2 anni dal trapianto Disease free survival (DFS) a 1 anno e 2 anni dal trapiantoCorrelazione immunofenotipica, citogenetica, molecolare e del profilo genomico da NGS con la sensibilità (CR/Cri/MLFS) .

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age> 60 - <75 years old
Diagnosis of AMS eligible for allogeneic hematopoietic stem cell transplantation from any donor High and intermediate ELN risk
WBC <25x10 ^ 9 / L (hydroxyurea is allowed to meet this criterion)
Adequate liver function (bilirubin =2 UNL; ALT / AST =2.5 UNL)
Adequate renal function (creatinine clearance =50 ml / min)
Status Performance status: ECOG <2
Men enrolled in the study with partners who are potentially fertile women must be willing to use an acceptable barrier method of contraception during the study.
Women of childbearing potential must use a highly effective contraceptive method for at least one month after the last dose of Venetoclax and for the time indicated in the EU SmPC for Decitabine
Availability and compliance with the requirements of the protocol
Signed informed consent

Età >60 - <75 anni
Diagnosi di LAM eleggibili a trapianto di cellule staminali emopoietiche allogeniche da qualsiasi donatore Rischio ELN alto e intermedio
WBC <25x10^9/L (l'idrossiurea è permessa per soddisfare questo criterio)
Adeguata funzionalità epatica (bilirubina =2 UNL; ALT/AST =2,5 UNL)
Adeguata funzionalità renale (clearance della creatinina =50 ml/min)
Performance status: ECOG < 2
Gli uomini arruolati nello studio con partner che sono donne potenzialmente fertili, devono essere disposti a utilizzare un metodo contraccettivo di barriera accettabile durante lo studio.
Le donne in età fertile devono utilizzare un metodo contraccettivo altamente efficace per almeno un mese dopo l’ultima dose di Venetoclax e per il tempo indicato nel EU SmPC per Decitabina
Disponibilità e compliance a quanto richiesto dal protocollo
Consenso informato firmato

E.4

Principal exclusion criteria

Previous therapy for LAM (except hydroxyurea, which is allowed) or for myelodysplatic syndrome
Presence of CNS localization
Absence of informed consent
Patients with AML t (15; 17); t (8; 21); inv (16) Low ELN risk
Adverse events of grade> 2 NCI-CTCAE (v. 5) at the time of enrollment
Important organ dysfunctions: ejection fraction of the left ventricle <40%, FEV1, FVC, DLCO <40% of predicted, LFT> 5 times higher than the normal limit, or creatinine clearance <40ml / min.
Evidence of active HBV or HCV infection (positive test for HBV DNA HCV RNA)
Patients with HIV infection
Active uncontrolled infections
Patients with other potentially life-threatening concomitant diseases
Subjects with known hypersensitivity to any of the medicinal components
Diagnosis of cancer in the 2 years preceding participation in the study, with the exception of:
- In situ carcinoma of the uterine cervix or breast adequately treated;
- Basal cell carcinoma of the skin or localized squamous skin carcinoma;
- Previous neoplasm localized and surgically resected (or treated in other ways)
Participation in another clinical trial within 1 month before the start of this trial

Precedente terapia per LAM (eccetto idrossiurea, che è permessa) o per Sindrome mielodisplatica
Presenza di localizzazione SNC
Assenza di consenso Informato
Pazienti con AML t(15;17); t(8;21); inv(16)Rischio ELN basso
Eventi avversi di grado >2 NCI-CTCAE (v. 5) al momento dell’arruolamento
Importanti disfunzioni d’organo: frazione di eiezione del ventricolo sinistro <40%, FEV1, FVC, DLCO <40% of predicted, LFT >5 volte superiore al limite di normalità, o clearance della creatinina <40ml/min.
Evidenza di infezione attiva da HBV o HCV (test positivo per HBV DNA HCV RNA)
Pazienti con infezione da HIV
Infezioni attive non controllate
Pazienti con altre malattie concomitanti potenzialmente letali
Soggetti con ipersensibilità nota a uno qualsiasi dei componenti medicinali
Diagnosi di neoplasia nei 2 anni precedenti la partecipazione allo studio, con l’eccezione di:
-Carcinoma in situ della cervice uterina o mammella adeguatamente trattati;
-Carcinoma basocellulare della cute o carcinoma squamoso cutaneo localizzato;
-Precedente neoplasia localizzata e resecata chirurgicamente (o trattata con altre modalità)
Partecipazione a un'altra sperimentazione clinica entro 1 mese prima dell'inizio di questa sperimentazione.

E.5 End points

E.5.1

Primary end point(s)

Number of elderly patients (aged> 60 - <75 years) with LAM, eligible for allo-SCT, treated with the "chemo-free" combination VEN-DEC who undergo allogeneic transplantation in the condition of CR / CRi / MLFS

Numero di pazienti anziani (età >60 - <75 anni) con LAM, eleggibili ad allo-SCT, trattati con la combinazione “chemo-free” VEN-DEC che vengono sottoposti a trapianto allogenico in condizione di CR/CRi/MLFS

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year and 2 years after transplanting

1 anno e a 2 anni dal trapianto

E.5.2

Secondary end point(s)

- Evaluation of the effectiveness of therapy with VEN-DEC
- Cumulative incidence of graft failure per day +30, +100 after transplantation - Outcome in terms of NRM per day +100, 1 year and 2 years after transplantation
- Cumulative incidence and severity of acute GVHD per day +100 after transplantation
- Cumulative incidence and severity of chronic GVHD 1 year and 2 years after transplantation
- RI 1 year and 2 years after transplantation
- OS 1 year and 2 years after transplantation
- DFS 1 year and 2 years after transplantation
- 1 year and 2 year probability of GRFS from transplantation
- Immunophenotypic, cytogenetic, molecular and genomic profile correlation from NGS with sensitivity (CR / Cri / MLFS) or resistance (PR / NR) to the "chemo-free" combination VEN-DEC
- Immunophenotypic, cytogenetic, molecular and genomic profile correlation from NGS with the outcome of the transplant in terms of NRM, RI, DFS and OS

- Valutazione dell’efficacia della terapia con VEN-DEC
- Incidenza cumulativa di graft failure al giorno +30, +100 dal trapianto- Outcome in termini di NRM al giorno +100, a 1 anno e a 2 anni dal trapianto
- Incidenza cumulativa e severità di GVHD acuta al giorno +100 dal trapianto
- Incidenza cumulativa e severità della GVHD cronica 1 anno e a 2 anni dal trapianto
- RI a 1 anno e 2 anni dal trapianto
- OS a 1 anno e 2 anni dal trapianto
- DFS a 1 anno e 2 anni dal trapianto
- Probabilità a 1 anno e 2 anni di GRFS dal trapianto
- Correlazione immunofenotipica, citogenetica, molecolare e del profilo genomico da NGS con la sensibilità (CR/Cri/MLFS) o resistenza (PR/NR) alla combinazione “chemo-free” VEN-DEC
- Correlazione immunofenotipica, citogenetica, molecolare e del profilo genomico da NGS con l’outcome del trapianto in termini di NRM, RI, DFS e OS

E.5.2.1

Timepoint(s) of evaluation of this end point

1 year and 2 years after transplanting

1 anno e a 2 anni dal trapianto

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

E.6.4

Safety

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

E.8.1.1

Randomised

E.8.1.2

Open

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

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.8.6 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

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

The study is considered completed upon enrollment of patient no. 100

Lo studio si ritiene completato all’arruolamento del paziente n. 100

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.1.1.1

In Utero

F.1.1.2

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

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

100

F.4.2.2

In the whole clinical trial

100

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)

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

2020-11-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-07

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials