Clinical trial • Phase II • Haematology

Venetoclax for Acute myeloid leukemia secondary to myeloproliferative neoplasms

Phase II trial of Venetoclax for Acute myeloid leukemia secondary to myeloproliferative neoplasms. None/Not specified-controlled. 101 participants.

Overview

Trial Therapeutic Area
Haematology
Trial Disease
Acute myeloid leukemia secondary to myeloproliferative neoplasms
Trial Stage
Phase II
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
07-06-2024
First CTIS Authorization Date
08-07-2024

Trial design

None/Not specified-controlled Phase II trial in Italy.

Comparator
None/Not specified
Target Sample Size
101
Trial Duration For Participant
365

Eligibility

Recruits 101 The record indicates isVulnerablePopulationSelected = true. Consent requirement: "Signed written informed consent according to ICH/EU/GCP and national local laws." Subject information and informed consent forms are listed in documents. No explicit mention of assent procedures or age-specific consent documents for minors..

Vulnerable Population
The record indicates isVulnerablePopulationSelected = true. Consent requirement: "Signed written informed consent according to ICH/EU/GCP and national local laws." Subject information and informed consent forms are listed in documents. No explicit mention of assent procedures or age-specific consent documents for minors.

Inclusion criteria

  • {"criterion_text":"- 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\n- Patients = 60 years or adult patients unfit for intensive treatment modalities at the discretion of the investigator.\n- ECOG performance status 0-2 or disease-related reversible ECOG 3 score following adequate supportive care.\n- Signed written informed consent according to ICH/EU/GCP and national local laws.\n- 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."}

Exclusion criteria

  • {"criterion_text":"- Diagnosis of de novo AML\n- 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.\n- 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.\n- Uncontrolled bacterial or fungal infections\n- QTc >470 msec on screening ECG (Fridericia's formula)\n- A history of cancer that is not in remission phase following surgery and/or chemotherapy and/or radiotherapy with life expectancy < 6 months."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"EFS defined as time from treatment start to primary refractory disease (no achievement of at least ALR-C after 2 courses), first relapse (if reached ALR-C) or death, whichever occurs first; measured at 1 year."}

Secondary endpoints

  • {"endpoint_text":"- 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","definition_or_measurement_approach":"Safety assessed by adverse events rate per CTCAE v5.0; rate of deaths in aplasia per ELN 2017; days to neutrophil and platelet recovery after cycles in responders."}
  • {"endpoint_text":"- 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)","definition_or_measurement_approach":"Responses categorized using ALR-C and ALR-P per post-MPN AML consortium definitions at specified time-points after cycles 1 and 2."}
  • {"endpoint_text":"- Efficacy of VEN-DEC regimen, as assessed by: 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)","definition_or_measurement_approach":"ORR after cycle 2 per post-MPN AML consortium; DFS and OS per ELN 2017 definitions; CIR measured as cumulative incidence of relapse."}
  • {"endpoint_text":"- Efficacy of VEN-DEC regimen, as assessed by: 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.","definition_or_measurement_approach":"TRM assessed as treatment-related mortality; transfusion need measured as number of RBC and platelet units transfused over 3 and 6 months according to institutional thresholds."}

Recruitment

Planned Sample Size
101
Recruitment Window Months
54
Consent Approach
Signed written informed consent according to ICH/EU/GCP and national local laws. Subject information and informed consent forms are listed in the trial documents (L1_SIS and ICF files). No explicit mention of assent procedures or multiple language versions in the available record.

Geography

Total Number Of Sites
31
Total Number Of Participants
101

Italy

Earliest CTIS Part Ii Submission Date
17-06-2024
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
679
Number Of Sites
31
Number Of Participants
101

Sites

Site Name
Careggi University Hospital
Department Name
DIPARTIMENTO DI MEDICINA SPERIMENTALE E CLINICA - SOD EMATOLOGIA
Principal Investigator Name
aLESSANDRO Vannucchi
Principal Investigator Email
amvannucchi@unifi.it
Contact Person Name
aLESSANDRO Vannucchi
Contact Person Email
amvannucchi@unifi.it
Site Name
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Department Name
DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE (DIMES) - UOC EMATOLOGIA
Principal Investigator Name
Antonio Curti
Principal Investigator Email
antonio.curti2@unibo.it
Contact Person Name
Antonio Curti
Contact Person Email
antonio.curti2@unibo.it
Site Name
Azienda Socio Sanitaria Territoriale Dei Sette Laghi
Department Name
DIPARTIMENTO DI MEDICINA SPECIALISTICA
Principal Investigator Name
Claudia Maria Basilico
Principal Investigator Email
claudiamaria.basilico@asst-settelaghi.it
Contact Person Name
Claudia Maria Basilico
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
DIPARTIMENTO DI MEDICINA CLINICA E CHIRURGIA - UOC EMATOLOGIA
Principal Investigator Name
Fabrizio Pane
Principal Investigator Email
fabrizio.pane@unina.it
Contact Person Name
Fabrizio Pane
Contact Person Email
fabrizio.pane@unina.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
DIPARTIMENTO DI ONCOLOGIA - SC EMATOLOGIA
Principal Investigator Name
Eloise Beggiato
Principal Investigator Email
ebeggiato@cittadellasalute.to.it
Contact Person Name
Eloise Beggiato
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
DIPARTIMENTO DI MEDICINA TRASLAZIONALE E DI PRECISIONE - UOC EMATOLOGIA
Principal Investigator Name
Massimo Breccia
Principal Investigator Email
breccia@bce.uniroma1.it
Contact Person Name
Massimo Breccia
Contact Person Email
breccia@bce.uniroma1.it
Site Name
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G Salesi
Department Name
DIPARTIMENTO DI EMATOLOGIA
Principal Investigator Name
Lorenzo Brunetti
Principal Investigator Email
lorenzo.brunetti@staff.univpm.it
Contact Person Name
Lorenzo Brunetti
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
DIPARTIMENTO ONCOEMATOLOGICO - UO EMATOLOGIA
Principal Investigator Name
Michela Rondoni
Principal Investigator Email
michela.rondoni@auslromagna.it
Contact Person Name
Michela Rondoni
Contact Person Email
michela.rondoni@auslromagna.it
Site Name
Azienda Ospedaliero-Universitaria Sant Andre
Department Name
DIPARTIMENTO SCIENZE ONCOLOGICHE - UOC EMATOLOgia
Principal Investigator Name
Agostino Tafuri
Principal Investigator Email
agostino.tafuri@ospedalesantandrea.it
Contact Person Name
Agostino Tafuri
Site Name
University Hospital Of Ferrara
Department Name
DIPARTIMENTO ONCOLOGICO MEDICO SPECIALISTICO - UOC EMATOLOGIA E FISIOPATOLOGIA DELLA COAGULAZIONE
Principal Investigator Name
Antonio Cuneo
Principal Investigator Email
cut@unife.it
Contact Person Name
Antonio Cuneo
Contact Person Email
cut@unife.it
Site Name
Azienda Ospedaliera Santa Croce E Carle
Department Name
SC EMATOLOGIA
Principal Investigator Name
Daniele Mattei
Principal Investigator Email
mattei.d@ospedale.cuneo.it
Contact Person Name
Daniele Mattei
Contact Person Email
mattei.d@ospedale.cuneo.it
Site Name
Azienda Ospedaliero Universitaria Di Modena
Department Name
DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, MATERNO-INFANTILI DELL'ADULTO - SC EMATOLOGIA
Principal Investigator Name
Mario Luppi
Principal Investigator Email
mario.luppi@unimore.it
Contact Person Name
Mario Luppi
Contact Person Email
mario.luppi@unimore.it
Site Name
IRCCS Ospedale Policlinico San Martino
Department Name
DIPARTIMENTO TERAPIE ONCOLOGICHE INTEGRATE - UO EMATOLOGIA E TRAPIANTI
Principal Investigator Name
Elisa Coviello
Principal Investigator Email
elisa.coviello@hsanmartino.it
Contact Person Name
Elisa Coviello
Contact Person Email
elisa.coviello@hsanmartino.it
Site Name
Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
Department Name
DIPARTIMENTO BIOMEDICO DI MEDICINA INTERNA E SPECIALISTICA - UO EMATOLOGIA
Principal Investigator Name
Sergio Siragusa
Principal Investigator Email
sergio.siragusa@unipa.it
Contact Person Name
Sergio Siragusa
Contact Person Email
sergio.siragusa@unipa.it
Site Name
Hospital Santa Maria Della Misericordia
Department Name
EMATOLOGIA E TRAPIANTO MIDOLLO OSSEO
Principal Investigator Name
Valeria Cardinali
Principal Investigator Email
valy984@yahoo.it
Contact Person Name
Valeria Cardinali
Contact Person Email
valy984@yahoo.it
Site Name
Azienda Sanitaria Locale Di Pescara
Department Name
DIPARTIMENTO ONCOLOGICO-EMATOLOGICO - UOC EMATOLOGIA CLINICA
Principal Investigator Name
Prassede Salutari
Principal Investigator Email
prassede.salutari@ausl.pe.it
Contact Person Name
Prassede Salutari
Contact Person Email
prassede.salutari@ausl.pe.it
Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Department Name
DIPARTIMENTO DI ONCOLOGIA ED EMATOLOGIA - SC EMATOLOGIA
Principal Investigator Name
Federico Lussana
Principal Investigator Email
flussana@asst-pg23.it
Contact Person Name
Federico Lussana
Contact Person Email
flussana@asst-pg23.it
Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Department Name
DIPARTIMENTO DI MEDICINA SPECIALISTICA - CLINICA EMATOLOGICA
Principal Investigator Name
Mario Tiribelli
Principal Investigator Email
mario.tiribelli@uniud.it
Contact Person Name
Mario Tiribelli
Contact Person Email
mario.tiribelli@uniud.it
Site Name
Belcolle Hospital
Department Name
DIPARTIMENTO ONCO-EMATOLOGICO - UOC EMATOLOGIA
Principal Investigator Name
Ambra Di Veroli
Principal Investigator Email
ambra.diveroli@asl.vt.it
Contact Person Name
Ambra Di Veroli
Contact Person Email
ambra.diveroli@asl.vt.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
DIPARTIMENTO DI ONCOLOGIA ED EMATOLOGIA - SC EMATOLOGIA 2
Principal Investigator Name
Ernesta Audisio
Principal Investigator Email
eaudisio@cittadellasalute.to.it
Contact Person Name
Ernesta Audisio
Site Name
Azienda Ospedaliera Ordine Mauriziano Di Torino
Department Name
DIPARTIMENTO DI SCIENZE CLINICHE E BIOLOGICHE - SCDU EMATOLOGIA
Principal Investigator Name
Daniela Cilloni
Principal Investigator Email
daniela.cilloni@unito.it
Contact Person Name
Daniela Cilloni
Contact Person Email
daniela.cilloni@unito.it
Site Name
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Department Name
DIPARTIMENTO ONCO-EMATOLOGICO E PNEUMOEMATOLOGICO
Principal Investigator Name
Mario Annunziata
Principal Investigator Email
mario.annunziata@aocardarelli.it
Contact Person Name
Mario Annunziata
Site Name
University Hospital Consorziale Policlinico
Department Name
DIPARTIMENTO DELL'EMERGENZA E DEI TRAPIANTI DI ORGANI (D.E.T.O.) UO EMATOLOGIA CON TRAPIANTO
Principal Investigator Name
Pellegrino Musto
Principal Investigator Email
pellegrino.musto@uniba.it
Contact Person Name
Pellegrino Musto
Contact Person Email
pellegrino.musto@uniba.it
Site Name
ARNAS G. Brotzu
Department Name
SC EMATOLOGIA E CTMO
Principal Investigator Name
Giovanni Caocci
Principal Investigator Email
giovanni.caocci@unica.it
Contact Person Name
Giovanni Caocci
Contact Person Email
giovanni.caocci@unica.it
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
DIPARTIMENTO DI MEDICINA - EMATOLOGIA TOR VERGATA
Principal Investigator Name
Adriano Venditti
Principal Investigator Email
adriano.venditti@uniroma2.it
Contact Person Name
Adriano Venditti
Contact Person Email
adriano.venditti@uniroma2.it
Site Name
Azienda Ospedaliera Nazionale Ss Antonio E Biagio E C Arrigo Alessandria
Department Name
DIPARTIMENTO INTERNISTICO E DI EMERGENZA-URGENZA E ACCETTAZIONE STRUTTURALE - SCDU EMATOLOGIA
Principal Investigator Name
Monia Marchetti
Principal Investigator Email
monia.marchetti@ospedale.al.it
Contact Person Name
Monia Marchetti
Contact Person Email
monia.marchetti@ospedale.al.it
Site Name
Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
Department Name
DIPARTIMENTO CHIR. GENERALE E SPECIALITA' MEDICO CHIRURGICHE - EMATOLOGIA CON TRAPIANTO DI MIDOLLO
Principal Investigator Name
Francesco Di Raimondo
Principal Investigator Email
diraimon@unict.it
Contact Person Name
Francesco Di Raimondo
Contact Person Email
diraimon@unict.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
DIPARTIMENTO DI DIAGNOSTICA PER IMMAGINI, RADIOTERAPIA ONCOLOGICA ED EMATOLOGIA - AREA EMATOLOGICA
Principal Investigator Name
Patrizia Chiusolo
Principal Investigator Email
patrizia.chiusolo@Unicatt.it
Contact Person Name
Patrizia Chiusolo
Contact Person Email
patrizia.chiusolo@Unicatt.it
Site Name
Azienda Sanitaria Locale Di Salerno
Department Name
EMATOLOGIA
Principal Investigator Name
Catello Califano
Principal Investigator Email
c.califano@aslsalerno.it
Contact Person Name
Catello Califano
Contact Person Email
c.califano@aslsalerno.it
Site Name
Istituto Oncologico Veneto
Department Name
DIPARTIMENTO DI MEDICINA CLINICA 1 - UOC ONCOEMATOLOGIA
Principal Investigator Name
Alessandra Sperotto
Principal Investigator Email
alessandra.sperotto@iov.veneto.it
Contact Person Name
Alessandra Sperotto
Site Name
Azienda Ospedaliera Universitaria Senese
Department Name
DIPARTIMENTO DI SCIENZE MEDICHE, CHIRURGICHE E NEUROSCIENZE
Principal Investigator Name
Monica Bocchia
Principal Investigator Email
bocchia@unisi.it
Contact Person Name
Monica Bocchia
Contact Person Email
bocchia@unisi.it

Sponsor

Primary sponsor

Full Name
Fondazione Gimema Franco Mandelli Onlus
Organisation Type
Health care
Country Of Registered Address
Italy

Third parties

  • {"country":"Italy","full_name":"Laboratorio CRIMM - Centro di Ricerca e Innovazione delle Malattie Mieloproliferative","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Health care"}

Investigational products

Investigational Product Name
Venclyxto 100 mg film-coated tablets
Active Substance
Venetoclax
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation (marketingAuthNumber EU/1/16/1138/005 present)
Maximum Dose
maxDailyDoseAmount 400 mg
Investigational Product Name
Venclyxto 50 mg film-coated tablets
Active Substance
Venetoclax
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation (marketingAuthNumber EU/1/16/1138/003 present)
Maximum Dose
maxDailyDoseAmount 200 mg
Investigational Product Name
Venclyxto 10 mg film-coated tablets
Active Substance
Venetoclax
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
Marketing authorisation (marketingAuthNumber EU/1/16/1138/001 present)
Maximum Dose
maxDailyDoseAmount 100 mg
Investigational Product Name
Dacogen 50 mg powder for concentrate for solution for infusion.
Active Substance
Decitabine
Modality
Small molecule
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
Marketing authorisation (marketingAuthNumber EU/1/12/792/001 present)
Orphan Designation
Yes
Maximum Dose
maxDailyDoseAmount 20 mg/m2; maxTotalDoseAmount 600 mg/m2
Combination Treatment
Yes

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