Clinical trial • Phase II • Oncology|Haematology

PONATINIB for BCR/ABL1-like acute lymphoblastic leukemia (Philadelphia chromosome-negative)

Phase II trial of PONATINIB for BCR/ABL1-like acute lymphoblastic leukemia (Philadelphia chromosome-negative). None/Not specified-controlled.

Overview

Trial Therapeutic Area
Oncology|Haematology
Trial Disease
BCR/ABL1-like acute lymphoblastic leukemia (Philadelphia chromosome-negative)
Trial Stage
Phase II
Drug Modality
Small molecule|Peptide/protein/enzyme

Key dates

Initial CTIS Submission Date
27-06-2024
First CTIS Authorization Date
16-07-2024

Trial design

None/Not specified-controlled Phase II trial across 36 sites in Italy.

Comparator
None/Not specified
Biomarker Stratified
True, biomarker: BCR/ABL1-like predictor (BCR/ABL1-like profile)
Target Sample Size
32

Eligibility

Recruits 32 Vulnerable population flag selected in the CTIS record. Participants are adults (Age 18-65). Signed informed consent is required "according to ICH/EU/GCP and national regulation". Subject information and informed consent form documents are listed in the application (multiple L1 documents: L1_SIS study_redacted, L1_ICF Study_redacted, L1_PP study_redacted, etc.). No details on assent or additional consent procedures are provided in the available data..

Pregnancy Exclusion
Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs. prior to administration of Ponatinib). Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ two effective reliable methods of birth control throughout the study and for up to 12 months following discontinuation of study drugs
Vulnerable Population
Vulnerable population flag selected in the CTIS record. Participants are adults (Age 18-65). Signed informed consent is required "according to ICH/EU/GCP and national regulation". Subject information and informed consent form documents are listed in the application (multiple L1 documents: L1_SIS study_redacted, L1_ICF Study_redacted, L1_PP study_redacted, etc.). No details on assent or additional consent procedures are provided in the available data.

Inclusion criteria

  • {"criterion_text":"- Age18-65 years.\n- De novo Ph+-like ALL, as defined by the BCR/ABL1-like predictor (13).\n- WHO score =2\n- Adequate liver function, as defined by the following criteria: total serum bilirubin =1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, alanine aminotransferase (ALT) =2.5 ×ULN or aspartate aminotransferase (AST) =2.5 x ULN or leukemia related.\n- Adequate pancreatic function as defined by serum lipase and amylase =1.5 × ULN or leukemia related\n- No history of dyslipidemia, thrombotic events or cardiac disease.\n- For females of childbearing potential, a negative pregnancy test must be documented. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from enrollment through 12 months after the end of treatment.\n- Signed informed consent, according to ICH/EU/GCP and national regulation."}

Exclusion criteria

  • {"criterion_text":"- WHO performance status >2.\n- Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.\n- Taking medications that are known to be associated with torsades de pointes\n- Gastrointestinal (GI) function impairment, or a GI disease that may significantly alter the absorption of study drugs.\n- Patients who are currently receiving treatment with any of the medications with potential to prolong QT interval (listed in Appendix F) if the medications cannot be either discontinued or switched to a different medication prior to starting study drug\n- Patients who have received any investigational drug = 4 weeks.\n- Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy\n- Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs. prior to administration of Ponatinib). Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ two effective reliable methods of birth control throughout the study and for up to 12 months following discontinuation of study drugs\n- Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention\n- Patients unwilling or unable to comply with the protocol\n- Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.\n- Creatinine levels > 2.5mg/dl or glomerular filtration rate (GFR) < 20 ml/min or proteinuria >3.5 g/day.\n- Active HBV or HCV hepatitis, or AST/ALT > 2.5 x ULN and bilirubin > 1.5 x ULN.\n- History of acute pancreatitis within 1 year of study or history of chronic pancreatitis.\n- History of alcohol abuse\n- Ongoing or active infections\n- Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).\n- Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to: - Any history of myocardial infarction, stroke, or revascularization, unstable angina or transient ischemic attack within 6 months prior to enrollment, - Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards, - History of clinically significant (as determined by the treating physician) atrial arrhythmia, - Any history of ventricular arrhythmia, - Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint of this study is to evaluate clinical response - in terms of MRD negativity rate after 3 cycles (TP2) in patients with BCR/ABL1-like ALL treated with a Ponatinib plus chemotherapy approach.","definition_or_measurement_approach":"MRD negativity rate measured after 3 cycles (timepoint TP2); clinical response defined by MRD negativity at TP2."}

Secondary endpoints

  • {"endpoint_text":"- The rate of MRD negativity at 2 timepoints TP1, TP3","definition_or_measurement_approach":"MRD negativity assessed at timepoints TP1 and TP3."}
  • {"endpoint_text":"- DFS at 24 months","definition_or_measurement_approach":"Disease-free survival measured at 24 months."}
  • {"endpoint_text":"- EFS at 24 months","definition_or_measurement_approach":"Event-free survival measured at 24 months."}
  • {"endpoint_text":"- CIR estimation from CR achievement at 24 months","definition_or_measurement_approach":"Cumulative incidence of relapse estimated from complete remission achievement, assessed at 24 months."}
  • {"endpoint_text":"- OS at 24 months","definition_or_measurement_approach":"Overall survival measured at 24 months."}
  • {"endpoint_text":"- Treatment-related mortality (TRM)","definition_or_measurement_approach":"Mortality attributed to treatment; measurement approach not further specified in available data."}
  • {"endpoint_text":"- Clinical response","definition_or_measurement_approach":"Clinical response (including CR rates); specific definitions not further detailed in the available CTIS record."}
  • {"endpoint_text":"- Feasibility of a combination approach with Ponatinib and chemotherapy","definition_or_measurement_approach":"Feasibility assessed by ability to administer and complete the combination regimen; detailed criteria not provided in available data."}
  • {"endpoint_text":"- Rate of Adverse Events (AEs) and Seriuos AEs related to Ponatinib","definition_or_measurement_approach":"Rate of AEs and serious AEs related to ponatinib; safety assessed per standard reporting but no additional measurement detail provided in the available CTIS data."}

Recruitment

Planned Sample Size
32
Recruitment Window Months
79
Consent Approach
Signed informed consent required according to ICH/EU/GCP and national regulation (inclusion criterion). Subject information and informed consent form documents are present in the application (multiple L1 documents). Participants are adults (18-65) so consent is provided by the participant. Document language evidence: translations/labels indicate Italian versions (IT). No further details on multi-language materials or remote consent are provided in the available data.

Geography

Total Number Of Sites
36
Total Number Of Participants
32

Italy

Earliest CTIS Part Ii Submission Date
22-12-2023
Latest Decision Or Authorization Date
13-05-2025
Processing Time Days
508
Number Of Sites
36
Number Of Participants
32

Sites

Site Name
Azienda Sanitaria Universitaria Friuli Centrale
Department Name
DIPARTIMENTO DI MEDICINA SPECIALISTICA
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
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Department Name
DIPARTIMENTO DI ONCOLOGIA CLINICA
Principal Investigator Name
Erika Borlenghi
Principal Investigator Email
erika.borlenghi@gmail.com
Contact Person Name
Erika Borlenghi
Contact Person Email
erika.borlenghi@gmail.com
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
DIPARTIMENTO ONCOEMATOLOGICO
Principal Investigator Name
Anna Maria Mianulli
Principal Investigator Email
amianulli@auslrn.net
Contact Person Name
Anna Maria Mianulli
Contact Person Email
amianulli@auslrn.net
Site Name
AORN San Giuseppe Moscati Avellino
Department Name
Onco-Ematologico
Principal Investigator Name
Lidia Santoro
Principal Investigator Email
lidiasantoro63@libero.it
Contact Person Name
Lidia Santoro
Contact Person Email
lidiasantoro63@libero.it
Site Name
Azienda Sanitaria Locale Di Pescara
Department Name
DIPARTIMENTO ONCOLOGICO-EMATOLOGICO
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
Careggi University Hospital
Department Name
DIPARTIMENTO DI MEDICINA SPERIMENTALE E CLINICA
Principal Investigator Name
Matteo Piccini
Principal Investigator Email
matt.piccini@gmail.com
Contact Person Name
Matteo Piccini
Contact Person Email
matt.piccini@gmail.com
Site Name
Azienda Unita Sanitaria Locale Di Piacenza
Department Name
DIPARTIMENTO ONCOLOGIA - EMATOLOGIA
Principal Investigator Name
Daniele Vallisa
Principal Investigator Email
d.vallisa@ausl.pc.it
Contact Person Name
Daniele Vallisa
Contact Person Email
d.vallisa@ausl.pc.it
Site Name
Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
Department Name
DIPARTIMENTO DI CHIRURGIA GENERALE E SPECIALITA' MEDICO CHIRURGICHE
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
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Department Name
DIMECS E DIPARTIMENTO ONCOLOGICO
Principal Investigator Name
Monia Lunghi
Principal Investigator Email
monia.lunghi@med.unipmn.it
Contact Person Name
Monia Lunghi
Contact Person Email
monia.lunghi@med.unipmn.it
Site Name
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Department Name
Dipartimento di Oncologia ed Ematologia
Principal Investigator Name
Alessandro Rambaldi
Principal Investigator Email
arambaldi@asst-pg23.it
Contact Person Name
Alessandro Rambaldi
Contact Person Email
arambaldi@asst-pg23.it
Site Name
Fondazione IRCCS Policlinico San Matteo
Department Name
DIPARTIMENTO ONCOLOGIA
Principal Investigator Name
Patrizia Zappasodi
Principal Investigator Email
p.zappasodi@smatteo.pv.it
Contact Person Name
Patrizia Zappasodi
Contact Person Email
p.zappasodi@smatteo.pv.it
Site Name
Azienda Unita Locale Socio Sanitaria N 8 Berica
Department Name
DIPARTIMENTO STRUTTURALE ONCOLOGIA CLINICA
Principal Investigator Name
Corinna Greco
Principal Investigator Email
corinna.greco@aulss8.veneto.it
Contact Person Name
Corinna Greco
Contact Person Email
corinna.greco@aulss8.veneto.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
Azienda Unita Sanitaria Locale Della Romagna
Department Name
DIPARTIMENTO ONCOEMATOLOGICO
Principal Investigator Name
Francesco Lanza
Principal Investigator Email
francesco.lanza@auslromagna.it
Contact Person Name
Francesco Lanza
Contact Person Email
francesco.lanza@auslromagna.it
Site Name
Ospedale San Raffaele S.r.l.
Department Name
AREA ONCOLOGICA
Principal Investigator Name
Sara Mastaglio
Principal Investigator Email
mastaglio.sara@hsr.it
Contact Person Name
Sara Mastaglio
Contact Person Email
mastaglio.sara@hsr.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)
Principal Investigator Name
Cristina Papayannidis
Principal Investigator Email
cristina.papayannidis@unibo.it
Contact Person Name
Cristina Papayannidis
Contact Person Email
cristina.papayannidis@unibo.it
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
Site Name
ULSS3 SERENISSIMA - Ospedale dell'Angelo di Mestre
Department Name
UO EMATOLOGIA
Principal Investigator Name
Cristina Skert
Principal Investigator Email
cristina.skert@aulss3.veneto.it
Contact Person Name
Cristina Skert
Site Name
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Department Name
DIPARTIMENTO DI EMATOLOGIA
Principal Investigator Name
Mario Annunziata
Principal Investigator Email
annun.mario@gmail.com
Contact Person Name
Mario Annunziata
Contact Person Email
annun.mario@gmail.com
Site Name
Azienda Ospedaliera Universitaria Federico II Di Napoli
Department Name
DIPARTIMENTO DI MEDICINA CLINICA E CHIRURGIA
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
University Hospital Of Ferrara
Department Name
DIPARTIMENTO ONCOLOGIA - EMATOLOGIA
Principal Investigator Name
Gian Matteo Rigolin
Principal Investigator Email
rglgmt@unife.it
Contact Person Name
Gian Matteo Rigolin
Contact Person Email
rglgmt@unife.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
DIPARTIMENTO DI DIAGNOSTICA PER IMMAGINI, RADIOTERAPIA ONCOLOGICA ED EMATOLOGIA
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 Ospedaliera Ordine Mauriziano Di Torino
Department Name
DIPARTIMENTO DI SCIENZE CLINICHE E BIOLOGICHE
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 Ospedale Niguarda Ca Granda
Department Name
DIPARTIMENTO DI EMATOLOGIA ED ONCOLOGIA
Principal Investigator Name
Valentina Mancini
Principal Investigator Email
valentina.mancini@ospedaleniguarda.it
Contact Person Name
Valentina Mancini
Site Name
Istituto Europeo di Oncologia - Milano
Department Name
DIVISIONE DI ONCOEMATOLOGIA
Principal Investigator Name
Enrico Derenzini
Principal Investigator Email
enrico.derenzini@ieo.it
Contact Person Name
Enrico Derenzini
Contact Person Email
enrico.derenzini@ieo.it
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
DIPARTIMENTO DI MEDICINA INTERNA
Principal Investigator Name
Nicola Fracchiolla
Principal Investigator Email
ns.fracchiolla@gmail.com
Contact Person Name
Nicola Fracchiolla
Contact Person Email
ns.fracchiolla@gmail.com
Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
DAI MEDICO GENERALE
Principal Investigator Name
Massimiliano Bonifacio
Principal Investigator Email
massimiliano.bonifacio@univr.it
Contact Person Name
Massimiliano Bonifacio
Site Name
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Department Name
DIPARTIMENTO DI MEDICINA TRASLAZIONALE E DI PRECISIONE
Principal Investigator Name
Sabina Chiaretti
Principal Investigator Email
chiaretti@bce.uniroma1.it
Contact Person Name
Sabina Chiaretti
Contact Person Email
chiaretti@bce.uniroma1.it
Site Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Department Name
DIPARTIMENTO DI ONCOLOGIA
Principal Investigator Name
Antonio Mulè
Principal Investigator Email
a.mule@villasofia.it
Contact Person Name
Antonio Mulè
Contact Person Email
a.mule@villasofia.it
Site Name
Azienda Ospedaliero Universitario Sant Andre
Department Name
DIPARTIMENTO SCIENZE ONCOLOGICHE
Principal Investigator Name
Agostino Tafuri
Principal Investigator Email
agostino.tafuri@ospedalesantandrea.it
Contact Person Name
Agostino Tafuri
Site Name
Azienda Ospedaliero Policlinico Universitario Tor Vergata
Department Name
DIPARTIMENTO DI MEDICINA
Principal Investigator Name
Maria Ilaria Del Principe
Principal Investigator Email
del.principe@med.uniroma2.it
Contact Person Name
Maria Ilaria Del Principe
Contact Person Email
del.principe@med.uniroma2.it
Site Name
Ospedale Vito Fazzi Lecce
Department Name
POLO ONCOLOGICO “GIOVANNI PAOLO II”
Principal Investigator Name
Nicola Di Renzo
Principal Investigator Email
direnzo.ematolecce@gmail.com
Contact Person Name
Nicola Di Renzo
Contact Person Email
direnzo.ematolecce@gmail.com
Site Name
Azienda Ospedale-Universita Padova
Department Name
DIPARTIMENTO DI EMATOLOGIA ED IMMUNOLOGIA CLINICA
Principal Investigator Name
Federica Lessi
Principal Investigator Email
lessi.federica@gmail.com
Contact Person Name
Federica Lessi
Contact Person Email
lessi.federica@gmail.com
Site Name
Hospital Santa Maria Della Misericordia
Department Name
DIPARTIMENTO DI MEDICINA E CHIRURGIA
Principal Investigator Name
Roberta La Starza
Principal Investigator Email
roberta.lastarza@unipg.it
Contact Person Name
Roberta La Starza
Contact Person Email
roberta.lastarza@unipg.it
Site Name
Fondazione Policlinico Universitario Campus Bio-Medico
Department Name
Divisione Ematologia
Principal Investigator Name
Daniele Armiento
Principal Investigator Email
d.armiento@unicampus.it
Contact Person Name
Daniele Armiento
Contact Person Email
d.armiento@unicampus.it
Site Name
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Department Name
DIPARTIMENTO DI ONCOLOGIA ED EMATOLOGIA
Principal Investigator Name
Ernesta Audisio
Principal Investigator Email
eaudisio@cittadellasalute.to.it
Contact Person Name
Ernesta Audisio

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 Ematologia, Azienda Policlinico \"Umberto I\", Diapartimento Medicina Traslaz. e di Precis","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Health care"}

Investigational products

Investigational Product Name
Iclusig 15 mg film-coated tablets
Active Substance
PONATINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Marketing authorisation (EU; EU/1/13/839/001 present in product data)
Starting Dose
15 mg
Maximum Dose
30 mg
Combination Treatment
Yes

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