AVAJAK: Apixaban/Rivaroxaban Versus Aspirin for Primary Prevention of Thrombo-embolic Complications in JAK2V617F-positive Myeloproliferative Neoplasms

NCT ID: NCT05198960

Last Updated: 2025-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1308 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-13

Study Completion Date

2027-07-13

Brief Summary

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Philadelphia-negative myeloproliferative neoplasms (MPN) are frequent and chronic myeloid malignancies including Polycythemia Vera (PV), essential thrombocythemia (ET), Primary Myelofibrosis (PMF) and Prefibrotic myelofibrosis (PreMF). These MPNs are caused by the acquisition of mutations affecting activation/proliferation pathways in hematopoietic stem cells. The principal mutations are JAK2V617F, calreticulin (CALR exon 9) and MPL W515. ET or MFP/PreMF patients who do not carry one of these three mutations are declared as triple-negative (3NEG) cases even if they are real MPN cases.

These diseases are at high risk of thrombo-embolic complications and with high morbidity/mortality. This risk varies from 4 to 30% depending on MPN subtype and mutational status.

In terms of therapy, all patients with MPNs should also take daily low-dose aspirin (LDA) as first antithrombotic drug, which is particularly efficient to reduce arterial but not venous events.

Despite the association of a cytoreductive drug and LDA, thromboses still occur in 5-8% patients/year.

All these situations have been explored in biological or clinical assays. All of them could increase the bleeding risk. We should look at different ways to reduce the thrombotic incidence: Direct Oral Anticoagulants (DOAC)? In the general population, in medical or surgical contexts, DOACs have demonstrated their efficiency to prevent or cure most of the venous or arterial thrombotic events.

At the present time, DOAC can be used in cancer populations according to International Society on Thrombosis and Haemostasis (ISTH) recommendations, except in patients with cancer at high bleeding risk (gastro-intestinal or genito-urinary cancers). Unfortunately, in trials evaluating DOAC in cancer patients, most patients have solid rather than hematologic cancers (generally less than 10% of the patients, mostly lymphoma or myeloma).

In cancer patients, DOAC are also highly efficient to reduce the incidence of thrombosis (-30 to 60%), but patients are exposed to a higher hemorrhagic risk, especially in digestive cancer patients.

In the cancer population, pathophysiology of both thrombotic and hemorrhagic events may be quite different between solid cancers and MPN. If MPN patients are also considered to be cancer patients in many countries, the pathophysiology of thrombosis is quite specific (hyperviscosity, platelet abnormalities, clonality, specific cytokines…) and they are exposed to a lower risk of digestive hemorrhages. It is thus difficult to extend findings from the "general cancer population" to MPN patients.

Unfortunately, only scarce, retrospective data regarding the use of DOAC in MPNs are available data.

We were the first to publish a "real-life" study about the use, the impact, and the risks in this population. In this local retrospective study, 25 patients with MPN were treated with DOAC for a median time of 2.1 years. We observed only one thrombosis (4%) and three major hemorrhages (12%, after trauma or unprepared surgery). Furthermore, we have compared the benefit/risk balance compared to patients treated with LDA without difference.

With the increasing evidences of efficacy and tolerance of DOAC in large cohorts of patients including cancer patients, with their proven efficacy on prevention of both arterial and venous thrombotic events and because of the absence of prospective trial using these drugs in MPN patients, we propose to study their potential benefit as primary thrombotic prevention in MPN.

Detailed Description

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Conditions

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Polycythemia Vera Essential Thrombocythemia Prefibrotic/Early Primary Myelofibrosis JAK2 V617F High-risk Patients

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

AVAJAK is an academic multicenter phase 3 prospective, randomized, and open label trial.

\> Randomization of the patients: Patients corresponding to inclusion criteria will be randomized based on a 1:1 distribution.

* Experimental group (Patients allocated to receive low-dose DOAC, at the choice of the investigator)

* Apixaban 2.5 mg BID or
* Rivaroxaban 10 mg OD, at the choice of the investigator.
* Control group (Patients allocated to receive LDA)

\- Aspirin 100 mg OD Dispensation of treatments every 6 months for 24 months
* Stratification:

* First stratification will be done by center
* Second stratification will be done by pathology (PV/ET/ PreMF)
* No stratification will be made based on DOAC drugs.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Experimental group

Patients randomized to receive Direct Oral Anticoagulants, at the choice of the investigator Apixaban 2.5 mg both in day or Rivaroxaban 10 mg one per day, at the choice of the investigator

Group Type EXPERIMENTAL

Direct Oral Anticoagulants

Intervention Type DRUG

Patients randomized to receive DOAC, at the choice of the investigator: Apixaban 2.5 mg both in day or Rivaroxaban 10 mg once daily.

Control group

Patients randomized to receive Low-Dose Aspirin Aspirin 100 mg one per day

Group Type ACTIVE_COMPARATOR

Low-dose aspirin

Intervention Type DRUG

Patients allocated to receive LDA: Aspirin 100 mg OD once daily.

Interventions

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Direct Oral Anticoagulants

Patients randomized to receive DOAC, at the choice of the investigator: Apixaban 2.5 mg both in day or Rivaroxaban 10 mg once daily.

Intervention Type DRUG

Low-dose aspirin

Patients allocated to receive LDA: Aspirin 100 mg OD once daily.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients with diagnosis of PV or ET or PreMF according to WHO or BSCH criteria (bone marrow biopsy not compulsory).
* Patients with JAK2V617F mutation (threshold allele burden \> 1%).
* 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.
* Length of time from MPN diagnostic to inclusion will not exceed 12 months.

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Brest

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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CHU d'Angers

Angers, , France

Site Status RECRUITING

CH d'Annecy

Annecy, , France

Site Status NOT_YET_RECRUITING

CH d'Argenteuil

Argenteuil, , France

Site Status NOT_YET_RECRUITING

CH d'Avignon

Avignon, , France

Site Status RECRUITING

CH de la Côte Basque Bayonne

Bayonne, , France

Site Status NOT_YET_RECRUITING

CH de Béziers

Béziers, , France

Site Status NOT_YET_RECRUITING

CHU Bordeaux

Bordeaux, , France

Site Status RECRUITING

CHU Brest

Brest, , France

Site Status RECRUITING

Hôpital privé Cesson-Sévigné

Cesson-Sévigné, , France

Site Status NOT_YET_RECRUITING

CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status NOT_YET_RECRUITING

Hôpital Henri Mondor (APHP)

Créteil, , France

Site Status RECRUITING

CHU Grenoble Alpes

Grenoble, , France

Site Status RECRUITING

CHD Vendée La Roche Sur Yon

La Roche-sur-Yon, , France

Site Status RECRUITING

CHU Le Havre

Le Havre, , France

Site Status NOT_YET_RECRUITING

CH Le Mans

Le Mans, , France

Site Status NOT_YET_RECRUITING

CH Libourne

Libourne, , France

Site Status NOT_YET_RECRUITING

CHU de Limoges - Hôpital Dupuytren

Limoges, , France

Site Status RECRUITING

Centre Léon Bérard Lyon

Lyon, , France

Site Status NOT_YET_RECRUITING

CHU de Montpellier

Montpellier, , France

Site Status NOT_YET_RECRUITING

CH de Morlaix

Morlaix, , France

Site Status RECRUITING

CHU de Nancy

Nancy, , France

Site Status RECRUITING

CHU de Nantes - Hôtel-Dieu

Nantes, , France

Site Status NOT_YET_RECRUITING

Hôpital Privé du Confluent Nantes

Nantes, , France

Site Status NOT_YET_RECRUITING

CHR d'Orléans

Orléans, , France

Site Status RECRUITING

Hôpital St-Louis (APHP)

Paris, , France

Site Status RECRUITING

Hôpital Cochin (APHP)

Paris, , France

Site Status NOT_YET_RECRUITING

CH de Perpignan

Perpignan, , France

Site Status NOT_YET_RECRUITING

CH de Périgueux

Périgueux, , France

Site Status RECRUITING

CHIC de Quimper

Quimper, , France

Site Status RECRUITING

CHU de Rennes

Rennes, , France

Site Status NOT_YET_RECRUITING

CH de Rochefort

Rochefort, , France

Site Status NOT_YET_RECRUITING

CH de Roubaix

Roubaix, , France

Site Status RECRUITING

Centre Henri Becquerel de Rouen

Rouen, , France

Site Status RECRUITING

CHU La Réunion - Site Nord Félix GUYON

Saint-Denis, , France

Site Status NOT_YET_RECRUITING

CHU La Réunion - Site Sud

Saint-Pierre, , France

Site Status NOT_YET_RECRUITING

Institut de Cancérologie Lucien Neuwirth St-Priest-en-Jarez

Saint-Priest-en-Jarez, , France

Site Status RECRUITING

Clinique Sainte Anne Strasbourg

Strasbourg, , France

Site Status NOT_YET_RECRUITING

CHU de Tours

Tours, , France

Site Status RECRUITING

CH Bretagne Atlantique Vannes

Vannes, , France

Site Status RECRUITING

CH de Versailles

Versailles, , France

Site Status NOT_YET_RECRUITING

CH Paul-Brousse (APHP)

Villejuif, , France

Site Status NOT_YET_RECRUITING

Médipôle Hôpital Mutualiste Villeurbanne

Villeurbanne, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Jean-Christophe IANOTTO, Pr

Role: CONTACT

+33298223421

Facility Contacts

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Corentin ORVAIN, PH

Role: primary

+33615270461

Anne PARRY, PH

Role: primary

+33450635101

Annalisa ANDREOLI, PH

Role: primary

Borhane SLAMA, PH

Role: primary

Frédéric BAUDUER, PH

Role: primary

Alain Radwan SAAD, PH

Role: primary

Clémence MEDIAVILLA, PH

Role: primary

Jean-Christophe Ianotto, PUPH

Role: primary

Benoît BAREAU, PH

Role: primary

Benoît DE RENZIS, PH

Role: primary

Lydia ROY, PH

Role: primary

Mathieu MEUNIER, PH

Role: primary

Bruno VILLEMAGNE, PH

Role: primary

Pierre LEBRETON, PH

Role: primary

Kamel LARIBI, PH

Role: primary

Diane LARA, PH

Role: primary

Amélie PENOT, PH

Role: primary

Franck-Emmanuel NICOLINI, PH

Role: primary

Franciane PAUL, PH

Role: primary

Christophe NICOL, PH

Role: primary

Dana RANTA, PH

Role: primary

Viviane DUBRUILLE, PH

Role: primary

Katell LE DU, PH

Role: primary

Marlène OCHMANN, PH

Role: primary

Jean-Jacques KILADJIAN, PUPH

Role: primary

Michaela FONTENAY, PH

Role: primary

Virginie ROLAND, PH

Role: primary

Claire CALMETTE, PH

Role: primary

Lénaïg LE CLECH, PH

Role: primary

Marc BERNARD, PH

Role: primary

Guillaume DENIS, PH

Role: primary

Mathieu WEMEAU, PH

Role: primary

Fabrice JARDIN, PH

Role: primary

Stéphane VANDERBECKEN, PH

Role: primary

Raphaëlle DINE, PH

Role: primary

Emilie CHALAYER, PH

Role: primary

Anaïse BLOUET, PH

Role: primary

Antoine MACHET, PH

Role: primary

Mélanie MERCIER, PH

Role: primary

Juliette LAMBERT, PH

Role: primary

Laurence LE GROS, PH

Role: primary

Mathias BREHON, PH

Role: primary

Other Identifiers

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29BRC20.0263 (AVAJAK)

Identifier Type: -

Identifier Source: org_study_id

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