Clinical Trials Register

Summary
EudraCT Number:	2020-006114-20
Sponsor's Protocol Code Number:	AML2420
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:	2021-07-27
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

2020-006114-20

A.3

Full title of the trial

A Phase 2, prospective, multi-center intervention trial in patients with acute myeloid leukemia secondary to myeloproliferative neoplasms unfit for intensive chemotherapy investigating a treatment combination including decitabine and venetoclax.
ENABLE (vENetoclax plus decitAbine treatment in Blastic phase of myeLoproliferative nEoplasms)

Studio interventistico di fase II, prospettico, multicentrico, in pazienti affetti da leucemia mieloide acuta secondaria a neoplasie mieloproliferative non eleggibili per chemioterapia intensiva, per valutare una terapia di combinazione con decitabina e venetoclax.
ENABLE (vENetoclax plus decitAbine treatment in Blastic phase of myeLoproliferative nEoplasms)

A.3.1

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

Study aimed at evaluating the efficacy of a combination treatment (decitabine and venetoclax) in patients with Acute Myeliode Leukemia who are ineligible or unresponsive to intensive chemotherapy.

Studio volto a valutare l'efficacia di un trattamento di associazione (decitabina e venetoclax) in pazienti affetti da Leucemia Mieliode Acuta che non sono idonei o non rispondono alla chemioterapia intensiva.

A.3.2

Name or abbreviated title of the trial where available

ENABLE

A.4.1

Sponsor's protocol code number

AML2420

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	FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
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	Fondazione Gimema Franco Mandelli Onlus
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	AbbVie Srl
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	Fondazione GIMEMA
B.5.2	Functional name of contact point	Centro Dati
B.5.3	Address:
B.5.3.1	Street Address	via Casilina, 5 Roma
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00182
B.5.3.4	Country	Italy
B.5.4	Telephone number	0670390526
B.5.5	Fax number	0670390540
B.5.6	E-mail	gimema@gimema.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	VENCLYXTO 100 MG- COMPRESSA RIVESTITA CON FILM- USO ORALE- BLISTER (PVC/PE/PCTFE-ALU)- 14 (7X2) COMP
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-coated 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.3.8	INN - Proposed INN	N-(5-(3,5-DIFLUOROBENZIL)-1H-INDAZOL-3-IL)-4-(4-METILPIPERAZIN-1-IL)-2-(TETRAIDRO-2H-PIRAN-4-ILAMINO)BENZAMIDE
D.3.9.1	CAS number	1257044-40-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Venetoclax
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	400
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	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	Venclyxto 100 mg compresse rivestite con film
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-coated 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.3.8	INN - Proposed INN	Venetoclax
D.3.9.1	CAS number	1257044-40-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Venetoclax
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	200
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: 3
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	Venclyxto 100 mg compresse rivestite con film
D.3.2	Product code	[NA]
D.3.4	Pharmaceutical form	Film-coated 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.3.8	INN - Proposed INN	Venetoclax
D.3.9.1	CAS number	1257044-40-8
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	Venetoclax
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	100
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

Acute Myeloid Leukemia secondary to myeloproliferative neoplasms

Leucemia Mieloide Acuta secondaria a neoplasie mieloproliferative

E.1.1.1

Medical condition in easily understood language

Secondary acute myeloid leukemia (AML) is an aggressive cancer caused by the uncontrolled multiplication of one of the immature cells (granulocytes) present in the bone marrow.

La leucemia mieloide acuta secondaria (Lma) è un tumore aggressivo causato dalla moltiplicazione incontrollata di una delle cellule immature (granulociti) presenti nel midollo osseo.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

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	10060355
E.1.2	Term	Acute myeloid leukaemia in remission
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	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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the trial is the efficacy of VEN-DEC regimen measured as event-free survival (EFS) in patients with AML secondary to MPN unfit for intensive chemotherapy.

L’obiettivo primario dello studio è valutare l’efficacia del trattamento con venetoclax e decitabina in termini di event-free survival (EFS) in pazienti affetti da leucemia acuta mieloide secondaria a neoplasie mieloproliferative, non eleggibili (unfit) per chemioterapia intensiva.

E.2.2

Secondary objectives of the trial

1. Feasibility and safety of VEN-DEC regimen, as assessed by: 1-adverse events rate according to CTCAE criteria; 2-rate of death in aplasia; 3-days to neutrophil recovery and 4-days to platelet recovery after first and second cycle
2. Efficacy of VEN-DEC regimen as assessed by: 1- Rate of Acute leukemia response-complete (ALR-C) at first time-point (T1) after first cycle (ALR-C-T1); 2-Overall response rate after first cycle [Acute leukemia response-complete (ALR-C-T1) + Acute leukemia response-partial (ALR-P-T1)]; 3- Rate of Acute leukemia response-complete at second time-point (T2) after second cycle (ALR-C-T2); 4- Overall response rate after second cycle [Acute leukemia response complete (ALR-C-T2) + Acute leukemia response-partial (ALR-P-T2)]; 5-Disease-free survival (DFS); 6-Overall survival (OS); 7-Cumulative incidence of relapse (CIR); 8- Treatment-related mortality (TRM); 9-Transfusion need (RBC and platelet) at 3 and 6 months of treatment

1. Fattibilità e sicurezza del trattamento con venetoclax e decitabina valutate tramite: 1-tasso di eventi avversi secondo i criteri CTCAE; 2-tasso di morte in aplasia; 3-giorni al recupero dei neutrofili e 4-giorni al recupero delle piastrine dopo il primo e il secondo ciclo.
2. Efficacia del regime VEN-DEC valutata tramite: 1- Tasso di risposta completa (Acute leukemia response-complete ALR-C) al primo time-point (T1) dopo il primo ciclo (ALR-C-T1); 2- Overall response rate (ORR) dopo il primo ciclo [ALR-C-T1 + Acute leukemia response-partial (ALR-P-T1)]; 3- Tasso di risposta completa al secondo time-point (T2) dopo il secondo ciclo (ALR-C-T2); 4- ORR dopo il secondo ciclo [ALR-C-T2 + ALR-P-T2]; 5-Disease-free survival (DFS); 6-Overall survival (OS); 7-Cumulative incidence of relapse (CIR); 8- Treatment-related mortality (TRM); 9- Necessità trasfusionale (globuli rossi e piastrine) a 3 e 6 mesi di trattamento.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacogenomics
Version: 1.0
Date: 24/08/2020
Title: Translational Research
Objectives: 1. To evaluate the prognostic impact of somatic mutations assessed at diagnosis on CR achievement and outcome (EFS, DFS, and OS) 2. To evaluate changes in the somatic mutational pattern from diagnosis to relapse 3. To evaluate the prognostic value of genetic abnormalities assessed by nanopore sequencing at baseline 4. To compare MRD by RT-PCR and MFC on paired BM and PB samples at scheduled time-points and their prognostic impact on outcome. 5. To study clonal dynamics of sAML subclones from diagnosis to relapse by single-cell analysis

Farmacogenomica
Versione: 1.0
Data: 24/08/2020
Titolo: Ricerca Traslazionale
Obiettivi: 1. Valutare l'impatto prognostico delle mutazioni somatiche valutate alla diagnosi sul raggiungimento della CR e risultato (EFS, DFS e OS) 2. Valutare i cambiamenti nel pattern mutazionale somatico dalla diagnosi alla ricaduta 3. Valutare il valore prognostico delle anomalie genetiche valutate mediante sequenziamento dei nanopori a linea di base 4. Per confrontare la MRD mediante RT-PCR e MFC su campioni di BM e PB accoppiati a intervalli temporali programmati e il loro impatto prognostico sui risultati. 5. Studiare la dinamica clonale dei subcloni sAML dalla diagnosi alla recidiva mediante analisi di singole cellule

E.3

Principal inclusion criteria

1. Patients with AML secondary to myeloproliferative neoplasms (sAML), untreated, newly diagnosed, according to WHO 2016 criteria based on conventional cytological, cytogenetic and immunophenotypic disease characterization
2. Patients = 60 years or adult patients unfit for intensive treatment modalities at the discretion of the investigator.
3. ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care.
4. Signed written informed consent according to ICH/EU/GCP and national local laws.
5. Males enrolled in the study with partners who are women of childbearing potential, must be willing to use an acceptable barrier contraceptive method during the trial. Males should use contraception for 3 months after the last dose of decitabine. Females should use contraception for 1 month after the last dose of venetoclax or 6 months after the last dose of decitabine, whichever comes later.

1. Pazienti con LMA secondaria a neoplasie mieloproliferative (sAML), non trattata, di nuova diagnosi, in accordo ai criteri dell'OMS 2016 basati sulla caratterizzazione citologica, citogenetica e immunofenotipica della malattia.
2. Pazienti di età = 60 anni o pazienti adulti unfit per modalità di trattamento intensive, a discrezione dello sperimentatore.
3. Performance status ECOG 0-2 o punteggio malattia-correlato ECOG 3 reversibile a seguito di una cura di supporto adeguata.
4. Consenso informato scritto firmato in accordo a ICH / EU / GCP e le leggi locali nazionali.
5. I pazienti uomini arruolati nello studio con partner donne potenzialmente fertili, devono essere disposti ad utilizzare un metodo contraccettivo di barriera accettabile durante lo studio. I pazienti uomini devono usare metodi contraccettivi per 3 mesi dopo l'ultima dose di decitabina. Le pazienti donne devono usare metodi contraccettivi per 1 mese dopo l'ultima dose di venetoclax o 6 mesi dopo l'ultima dose di decitabina, a seconda dell'evento che si verifica dopo.

E.4

Principal exclusion criteria

1. Diagnosis of de novo AML
2. Pre-existing, uncontrolled pathology such as heart failure (congestive/ischaemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), sever liver disease with total bilirubin >2,5 x ULN and/or ALT>3 ULN (unless attributable to AML), acute or chronic pancreatitis, kidney function impairment with Creatinine Clearance (CrCl) level <30ml/min (calculated by Cockcroft Gault formula)(unless attributable to AML) and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent or to cope with the intended treatment plan. For altered liver, pancreas and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures.
3. Pre-existing HIV positive serology (i.e. already known before enrolment). The participation to the study will require serology testing for HIV positivity at baseline: in case of HIV positivity or refusal to perform HIV testing, the patient will be considered not eligible.
4. Uncontrolled bacterial or fungal infections
5. QTc >470 msec on screening ECG (Fridericia's formula)
6. A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 6 months.

1. Diagnosi di LMA de novo
2. Patologia preesistente ed incontrollata come insufficienza cardiaca (congestizia/ischemica, infarto del miocardio acuto entro i 3 mesi precedenti, aritmie non trattabili, classi NYHA III e IV), grave malattia epatica con bilirubina totale > 2,5 x ULN e/o ALT> 3 ULN (a meno che non sia attribuibile alla LMA), pancreatite acuta o cronica, funzionalità renale compromessa con livello di clearance della creatinina (CrCl) < 30 ml/min (calcolato dalla formula di Cockcroft Gault) (a meno che non sia attribuibile alla LMA) e grave disturbo neuropsichiatrico che altera la capacità del paziente di comprendere e firmare il consenso informato o far fronte al piano di trattamento previsto. Per test di funzionalità epatica, pancreatica e renale alterata, i criteri di eleggibilità possono essere rivalutati a 24-96 ore, a seguito della istituzione di adeguate misure di supporto.
3. Sierologia HIV positiva preesistente (ovvero già nota prima dell'arruolamento). La partecipazione allo studio richiederà un test sierologico per HIV al baseline: in caso di positività all'HIV o rifiuto ad eseguire il test HIV, il paziente sarà considerato non idoneo.
4. Infezioni batteriche o fungine incontrollate
5. QTc> 470 msec all'ECG di screening (formula di Fridericia)
6. Storia di cancro non in fase di remissione a seguito di intervento chirurgico e/o chemioterapia e/o radioterapia, con aspettativa di vita <6 mesi.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is to evaluate the event free survival (EFS) at 1 year of an experimental VEN-DEC combination arm in patients with AML secondary to MPN and unfit for intensive therapeutic strategy. EFS is defined as the time between the date of treatment start and the date of either primary refractory disease (no achievement of at least ALR-C after 2 courses of treatment), first relapse (in patients who
reached ALR-C) or death (whatever the cause), whichever occurs first.

L'endpoint primario è valutare la sopravvivenza libera da eventi (EFS) a 1 anno dal trattamento VEN-DEC combinato nel braccio sperimentale in pazienti con LMA secondaria a MPN e non idonei per una strategia terapeutica intensiva. EFS è definito come il tempo tra la data di inizio del trattamento e la data di uno dei refrattari primari della malattia (nessun raggiungimento di almeno ALR-C dopo 2 cicli di trattamento), prima ricaduta (in pazienti che raggiunto ALR-C) o morte (qualunque sia la causa), a seconda di quale si verifica per prima.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 year after the start of treatment

A 1 anno dall'inizio del trattamento

E.5.2

Secondary end point(s)

1. Feasibility and safety of VEN-DEC regimen, as assessed by:
1. Adverse events rate as per v5.0 CTCAE criteria
2. Rate of deaths in aplasia as per ELN 2017 definition
3. Days to neutrophils recovery after first and second cycle in responding patients
4. Days to platelets recovery after first and second cycle in responding patients
2. Efficacy of VEN-DEC regimen, as assessed by:
1. Response rate categorized as at least Acute leukemia response-complete at first time-point after first cycle (ALR-C-T1)
2. Overall response rate at first time-point after first cycle categorized as ALR-C-T1 + ALR-P-T1 as per post-MPN AML consortium definition
3. Response rate categorized as at least ALR-C at secondo time-point after second cycle (ALR-C-T2)
4. Overall response rate after second cycle categorized as ALR-C-T2 + ALR-P-T2 as per post-MPN AML consortium definition
5. Disease-free survival (DFS) as per ELN 2017 definition
6. Overall survival (OS) as per ELN 2017 definition
7. Cumulative incidence of relapse (CIR)
8. Treatment-related mortality (TRM)
9. Transfusion need as defined as number of RBC and platelet units transfused over a period of 3 and 6 months of treatment as per institutional thresholds for transfusion support in hematological neoplasms.

1. Fattibilità e sicurezza del regime VEN-DEC, valutate da:
1. Tasso di eventi avversi secondo i criteri CTCAE v5.0
2. Tasso di decessi per aplasia secondo la definizione ELN 2017
3. Giorni al recupero dei neutrofili dopo il primo e il secondo ciclo nei pazienti che rispondono
4. Giorni al recupero delle piastrine dopo il primo e il secondo ciclo nei pazienti che hanno risposto
2. Efficacia del regime VEN-DEC, valutata da:
1. Tasso di risposta classificato come almeno risposta della leucemia acuta completa al primo punto temporale dopo il primo ciclo (ALR-C-T1)
2. Tasso di risposta globale al primo punto temporale dopo il primo ciclo classificato come ALR-C-T1 + ALR-P-T1 secondo la definizione del consorzio AML post-MPN
3. Tasso di risposta classificato come almeno ALR-C al secondo punto temporale dopo il secondo ciclo (ALR-C-T2)
4. Tasso di risposta globale dopo il secondo ciclo classificato come ALR-C-T2 + ALR-P-T2 secondo la definizione del consorzio AML post-MPN
5. Sopravvivenza libera da malattia (DFS) come da definizione ELN 2017
6. Sopravvivenza globale (OS) come da definizione ELN 2017
7. Incidenza cumulativa di recidiva (CIR)
8. Mortalità correlata al trattamento (TRM)
9. Necessità trasfusionale definita come numero di globuli rossi e unità piastriniche trasfuse in un periodo di 3 e 6 mesi di trattamento secondo le soglie istituzionali per il supporto trasfusionale nelle neoplasie ematologiche.

E.5.2.1

Timepoint(s) of evaluation of this end point

After the first and after the second course of treatment.

Dopo il primo e dopo il secondo ciclo di trattamento.

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

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)

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

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

Last visit of the last enrolled patient.

Ultima visita dell'ultimo paziente arruolato.

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)

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

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

101

F.4.2

For a multinational trial

F.4.2.1

In the EEA

101

F.4.2.2

In the whole clinical trial

101

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 will continue to be followed according to the normal care activity provided by good clinical practice.

I pazienti continueranno ad essere seguiti secondo la normale attività assistenziale prevista dalla buona pratica clinica.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Fondazione GIMEMA
G.4.3.4	Network Country	Italy

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-09-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-28

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

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Orphan Designation Number:
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