Clinical trial • Phase III • Oncology

APIXABAN for Philadelphia-negative myeloproliferative neoplasms | Polycythemia Vera | Essential thrombocythemia | Primary myelofibrosis | Prefibrotic myelofibrosis

Phase III trial of APIXABAN for Philadelphia-negative myeloproliferative neoplasms | Polycythemia Vera | Essential thrombocythemia | Primary myelofibrosis…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Philadelphia-negative myeloproliferative neoplasms | Polycythemia Vera | Essential thrombocythemia | Primary myelofibrosis | Prefibrotic myelofibrosis
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
04-07-2024
First CTIS Authorization Date
01-08-2024

Trial design

Randomised, low-dose aspirin (low-dose acetylsalicylic acid) — product examples listed: aspirine protect 100 mg (gastro-resistant), resitune 100 mg (gastro-resistant), acide acetylsalicylique viatris 100 mg (gastro-resistant), aspirine arrow 100 mg (gastro-resistant).-controlled Phase III trial in France.

Randomised
Yes
Comparator
Low-dose aspirin (low-dose acetylsalicylic acid) — product examples listed: ASPIRINE PROTECT 100 mg (gastro-resistant), RESITUNE 100 mg (gastro-resistant), ACIDE ACETYLSALICYLIQUE VIATRIS 100 mg (gastro-resistant), ASPIRINE ARROW 100 mg (gastro-resistant).
Target Sample Size
1008
Trial Duration For Participant
730

Eligibility

Recruits 1008 Patients under curatorship/guardianship are excluded; 'Inability to give informed consent' is an exclusion criterion. The trial does not select vulnerable populations and informed consent is required from adult participants (≥18); no paediatric assent procedures are described..

Pregnancy Exclusion
No appropriate contraception (estrogen contraception or no contraception) in women of childbearing age or breastfeeding woman; Planned pregnancy within 24 months
Vulnerable Population
Patients under curatorship/guardianship are excluded; 'Inability to give informed consent' is an exclusion criterion. The trial does not select vulnerable populations and informed consent is required from adult participants (≥18); no paediatric assent procedures are described.

Inclusion criteria

  • {"criterion_text":"- Patients with diagnosis of Polycythemia Vera or Essential Thrombocythemia or Prefibrotic myelofibrosis according to WHO or BSCH criteria (bone marrow biopsy not compulsory)."}
  • {"criterion_text":"- Patients with JAK2V617F mutation (threshold allele burden > 1%)."}
  • {"criterion_text":"- Patients considered as “high-risk” patients: - 1°) based on age (> 60-year-old) - 2°) based on thrombotic history (compatible with antithrombotic randomization) but aged ≥ 18-year-old"}
  • {"criterion_text":"- Length of time from MPN diagnostic to inclusion will not exceed 12 months"}

Exclusion criteria

  • {"criterion_text":"- Contra-indication to aspirin or DOAC due to allergic situation or recent history of major bleeding"}
  • {"criterion_text":"- No appropriate contraception (estrogen contraception or no contraception) in women of childbearing age or breastfeeding woman"}
  • {"criterion_text":"- PS>2 or life expectancy <12 months"}
  • {"criterion_text":"- Formal indication of treatment with LDA or DOAC (thus precluding randomization)"}
  • {"criterion_text":"- Inability to give informed consent"}
  • {"criterion_text":"- Patients under curatorship/guardianship"}
  • {"criterion_text":"- Concomitant use of a strong inhibitor or inducer of CYP3A4 (like Ruxolitinib)"}
  • {"criterion_text":"- Chronic liver disease or chronic hepatitis"}
  • {"criterion_text":"- Renal insufficiency with creatinine <30 ml/mn on Cockcroft and Gault Formula"}
  • {"criterion_text":"- Patient considered at high-risk of bleeding: patients with current or recent major or clinically relevant non major bleeding gastrointestinal or cerebral bleedings"}
  • {"criterion_text":"- Planned pregnancy within 24 months"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Time to occurrence of arterial or venous thromboembolic events","definition_or_measurement_approach":"Time-to-event (time to occurrence of arterial or venous thromboembolic events)"}

Secondary endpoints

  • {"endpoint_text":"- Time to occurrence of major and clinically relevant non-major bleedings as defined by ISTH","definition_or_measurement_approach":"Time-to-event; bleeding defined as per ISTH criteria"}
  • {"endpoint_text":"- Time to occurrence of arterial thromboembolic events","definition_or_measurement_approach":"Time-to-event for arterial thromboembolic events"}
  • {"endpoint_text":"- Time to occurrence of venous thromboembolic events","definition_or_measurement_approach":"Time-to-event for venous thromboembolic events"}
  • {"endpoint_text":"- Time to occurrence of thromboembolic and bleeding events according to PV or ET or PreMF status","definition_or_measurement_approach":"Time-to-event stratified by MPN subtype (PV, ET, PreMF)"}
  • {"endpoint_text":"- Time to occurrence of thromboembolic and bleeding events according to the cytoreductive associated drugs","definition_or_measurement_approach":"Time-to-event stratified by concomitant cytoreductive drug use"}
  • {"endpoint_text":"- Time to occurrence of serious adverse events others than thromboses and hemorrhages","definition_or_measurement_approach":"Time-to-event for serious adverse events excluding thrombotic and hemorrhagic events"}
  • {"endpoint_text":"- Occurrence of atrial fibrillation episodes (time to occurrence)","definition_or_measurement_approach":"Time-to-event for first occurrence of atrial fibrillation episodes"}
  • {"endpoint_text":"- Overall survival and event free survival (events defined above) at 24 months","definition_or_measurement_approach":"Survival analyses (overall survival and event-free survival) evaluated at 24 months"}
  • {"endpoint_text":"- Adjudicated mortality (non-cardiovascular and cardiovascular), time to occurence","definition_or_measurement_approach":"Time-to-event to adjudicated causes of death (cardiovascular and non-cardiovascular)"}
  • {"endpoint_text":"- Therapeutic adherence will be studied (Girerd auto-questionnaire) during the study treatment period of 24 months","definition_or_measurement_approach":"Adherence assessed using the Girerd self-questionnaire over 24 months"}
  • {"endpoint_text":"- Quality of life will be studied (EQ-5D-5L and MPN-SAF-TSS auto-questionnaire) during the study treatment period of 24 months","definition_or_measurement_approach":"Quality of life measured by EQ-5D-5L and MPN-SAF-TSS patient-reported questionnaires over 24 months"}
  • {"endpoint_text":"- Evaluation of costs and incremental cost utility ratio (cost per QALY) of low-dose DOAC compared to LDA","definition_or_measurement_approach":"Health economic evaluation including cost and incremental cost-utility ratio (cost per QALY) comparing low-dose DOAC vs LDA"}

Recruitment

Planned Sample Size
1008
Recruitment Window Months
84
Consent Approach
Informed consent is required from adult participants; a Subject Information Sheet and Informed Consent Form for adults is provided (document: L1_SIS and ICF adults). 'Inability to give informed consent' is an exclusion. No paediatric consent/assent procedures or languages are specified.

Geography

Total Number Of Sites
40
Total Number Of Participants
1008

France

Earliest CTIS Part Ii Submission Date
09-07-2024
Latest Decision Or Authorization Date
11-07-2025
Processing Time Days
367
Number Of Sites
40
Number Of Participants
1008

Sites

Site Name
Centre Hospitalier De La Cote Basque
Department Name
Hématologie
Contact Person Name
Frédéric BAUDUER
Contact Person Email
frederic.bauduer@u-bordeaux.fr
Site Name
Institut de Cancérologie Lucien Neuwirth
Department Name
Hématologie
Contact Person Name
Emilie CHALAYER
Contact Person Email
emilie.chalayer@icloire.fr
Site Name
Centre Hospitalier De Roubaix
Department Name
Hématologie
Contact Person Name
Mathieu WEMEAU
Contact Person Email
mathieu.wemeau@ch-roubaix.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Hématologie Clinique
Contact Person Name
Mathieu MEUNIER
Contact Person Email
mmeunier2@chu-grenoble.fr
Site Name
Centre Hospitalier D Avignon
Department Name
Onco-Hématologie
Contact Person Name
Borhane SLAMA
Contact Person Email
bslama@ch-avignon.fr
Site Name
CHU Nancy - Hôpital Brabois
Department Name
Service de Médecine Interne et Hématologie
Contact Person Name
Dana RANTA
Contact Person Email
d.ranta@chu-nancy.fr
Site Name
Hopital Cochin Saint Vincent De Paul
Department Name
Hématologie biologique
Contact Person Name
Michaela FONTENAY
Contact Person Email
michaela.fontenay@aphp.fr
Site Name
Centre Hospitalier De Perigueux
Department Name
Oncologie Hématologie
Contact Person Name
Claire CALMETTE
Site Name
Centre Hospitalier De Rochefort
Department Name
Médecine Interne et Hématologie
Contact Person Name
Guillaume DENIS
Site Name
Centre Hospitalier Victor Dupouy
Department Name
Hématologie
Contact Person Name
Annalisa ANDREOLI
Site Name
Clinique Sainte-Anne
Department Name
d'Oncologie-Hématologie
Contact Person Name
Anaïse BLOUET
Contact Person Email
ablouet@solcrr.org
Site Name
Hopital Saint Louis
Department Name
Centre d'Investigation Clinique
Contact Person Name
Jean-Jacques KILADJIAN
Contact Person Email
jean-jacques.kiladjian@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Onco-hématologie
Contact Person Name
Geoffroy VENTON
Contact Person Email
geoffroy.venton@aphm.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Hématologie
Contact Person Name
Marc BERNARD
Contact Person Email
marc.bernard@chu-rennes.fr
Site Name
Centre Hospitalier de Béziers
Department Name
Hématologie
Contact Person Name
Alain Radwan SAAD
Contact Person Email
alain.saad@ch-beziers.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Hématologie Clinique
Contact Person Name
Franciane PAUL
Contact Person Email
f-paul@chu-montpellier.fr
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
Service Maladie du Sang
Contact Person Name
Corentin ORVAIN
Contact Person Email
corentin.orvain@chu-angers.fr
Site Name
Centre Hospitalier Regional Et Universitaire De Brest
Department Name
Hématologie
Contact Person Name
Jean-Christophe IANOTTO
Site Name
Hopital Prive Sevigne
Department Name
Hématologie
Contact Person Name
Benoît BAREAU
Contact Person Email
benoit.bareau@gmail.com
Site Name
Centre Hospitalier Le Mans
Department Name
Hémato-oncologie
Contact Person Name
Kamel LARIBI
Contact Person Email
klaribi@ch-lemans.fr
Site Name
Centre Hospitalier Intercommunal De Mont De Marsan Et Du Pays Des Sources
Department Name
Oncologie
Contact Person Name
Samia MADENE HAROUNE
Contact Person Email
samia.madene@ch-mdm.fr
Site Name
Centre Hospitalier Departemental Vendee
Department Name
Onco-Hématologie
Contact Person Name
Bruno VILLEMAGNE
Contact Person Email
bruno.villemagne@chd-vendee.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Hématologie
Contact Person Name
Clémence MEDIAVILLA
Site Name
Centre Hospitalier Bretagne Atlantique
Department Name
Médecine interne- Hématologie - Maladies infectieuses
Contact Person Name
Mélanie MERCIER
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Hématologie
Contact Person Name
Antoine MACHET
Contact Person Email
a.machet@chu-tours.fr
Site Name
Groupe Hospitalier du Havre
Department Name
Onco-Hématologie
Contact Person Name
Pierre LEBRETON
Contact Person Email
pierre.lebreton@ch-havre.fr
Site Name
Hôpital Privé du Confluent
Department Name
Hématologie
Contact Person Name
Katell LE DU
Contact Person Email
dr.ledu@groupeconfluent.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Hématologie Clinique
Contact Person Name
Amélie PENOT
Contact Person Email
amelie.penot@chu-limoges.fr
Site Name
Centre Hospitalier Universitaire d’Orléans
Department Name
Hématologie clinique thérapie cellulaire
Contact Person Name
Marlène OCHMANN
Contact Person Email
marlene.ochmann@chr-orleans.fr
Site Name
CHU d'Estaing
Department Name
Hématologie Clinique
Contact Person Name
Benoît DE RENZIS
Site Name
Centre Hospitalier Universitaire de la Réunion - Site Sud
Department Name
Hématologie et d'oncologie clinique
Contact Person Name
Raphaëlle DINE
Contact Person Email
raphaelle.dine@chu-reunion.fr
Site Name
Centre Hospitalier Annecy Genevois
Department Name
Hématologie
Contact Person Name
Anne PARRY
Contact Person Email
aparry@ch-annecygenevois.fr
Site Name
Centre Hospitalier Des Pays De Morlaix
Department Name
Hématologie
Contact Person Name
Christophe NICOL
Contact Person Email
cnicol@ch-morlaix.fr
Site Name
Centre Leon Berard
Department Name
Onco-médicale
Contact Person Name
Franck-Emmanuel NICOLINI
Site Name
Centre Hospitalier De Perpignan
Department Name
Hématologie Clinique
Contact Person Name
Virginie ROLAND
Site Name
Centre Hospitalier De Libourne Robert Boulin
Department Name
Hématologie
Contact Person Name
Diane LARA
Contact Person Email
Diane.Lara@ch-libourne.fr
Site Name
Centre Hospitalier De Versailles
Department Name
Hématologie
Contact Person Name
Juliette LAMBERT
Contact Person Email
jlambert@ch-versailles.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Hématologie
Contact Person Name
Viviane DUBRUILLE
Site Name
Hopital Henri Mondor - 1 rue Gustave Eiffel
Department Name
Hématologie Clinique
Contact Person Name
Lydia ROY
Contact Person Email
lydia.roy@aphp.fr
Site Name
Centre Henri Becquerel
Department Name
Centre de lutte contre le cancer
Contact Person Name
Fabrice JARDIN
Site Name
Centre Hospitalier Universitaire De La Reunion
Department Name
Hémato-oncologie
Contact Person Name
Stéphane VANDERBECKEN
Site Name
Centre Hospitalier Intercommunal De Cornouaille
Department Name
Médecine Interne
Contact Person Name
Lénaïg LE CLECH
Contact Person Email
l.leclech@ch-cornouaille.fr
Site Name
Médipôle Hôpital Mutualiste Villeurbanne
Department Name
Hématologie
Contact Person Name
Mathias BREHON
Contact Person Email
m.brehon@resamut.fr
Site Name
Hopital Paul Brousse
Department Name
Hématologie
Contact Person Name
Laurence LEGROS
Contact Person Email
laurence.legros@aphp.fr

Sponsor

Primary sponsor

Full Name
Centre Hospitalier Regional Et Universitaire De Brest
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
Eliquis 2.5 mg film-coated tablets
Active Substance
APIXABAN
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised
Starting Dose
2.5 mg (tablet strength listed)
Maximum Dose
5 mg (maxDailyDoseAmount)
Investigational Product Name
Xarelto 10 mg film-coated tablets
Active Substance
RIVAROXABAN
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised
Starting Dose
10 mg (tablet strength listed)
Maximum Dose
10 mg (maxDailyDoseAmount)
Investigational Product Name
RESITUNE 100 mg, comprimé gastro-résistant
Active Substance
ACETYLSALICYLIC ACID
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised
Starting Dose
100 mg (tablet strength listed)
Maximum Dose
300 mg (maxDailyDoseAmount)
Investigational Product Name
ASPIRINE PROTECT 100 mg, comprimé gastro-resistant
Active Substance
ACETYLSALICYLIC ACID
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised
Starting Dose
100 mg (tablet strength listed)
Maximum Dose
300 mg (maxDailyDoseAmount)
Investigational Product Name
ACIDE ACETYLSALICYLIQUE VIATRIS 100 mg, comprimé gastro-résistant
Active Substance
ACETYLSALICYLIC ACID
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised
Starting Dose
100 mg (tablet strength listed)
Maximum Dose
100 mg (maxDailyDoseAmount)
Investigational Product Name
ASPIRINE ARROW 100 mg, comprimé gastro-résistant
Active Substance
ACETYLSALICYLIC ACID
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL
Authorisation Status
Authorised
Starting Dose
100 mg (tablet strength listed)
Maximum Dose
100 mg (maxDailyDoseAmount)

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