Etude : PEVONEDISTAT 3001 /

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Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : PEVONEDISTAT 3001

Situation thérapeutique :

Traitement :

Cadre réglementaire : RIPH2

Dernière MÀJ : 13/01/2021
CIM10 - Localisation(s)
Informations principales
Titre : Étude clinique de phase 3 en ouvert, randomisée et contrôlée visant à évaluer le Pevonedistat associé à l’Azacitidine comparé à l'Azacitidine seule comme traitement de première ligne chez les patients présentant des syndromes myélodysplasiques de haut risque, une leucémie myélomonocytaire chronique, ou une leucémie myéloïde aiguë avec faible blastose médullaire

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C92 - Leucémie myéloïde

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C93 - Leucémie monocytaire

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C96 - Tumeurs malignes des tissus lymphoïde, hématopoïétique et apparentés, autres et non précisées
Informations complémentaires
Schéma : The purpose of this study is to determine whether the combination of pevonedistat and azacitidine improves overall response rate (ORR) by Cycle 6 and whether the combination of pevonedistat and azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine.

The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to treat people with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (AML) as a combination treatment with azacitidine. This study will look at the overall survival, event-free survival and response to treatment in people who take pevonedistat and azacitidine when compared to people who take single-agent azacitidine.

The study will enroll approximately 450 patients. Once enrolled, participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups in 28-day treatment cycles:

Pevonedistat 20 mg/m^2 and azacitidine 75 mg/m^2 combination
Single-agent azacitidine 75 mg/m^2
All participants will receive azacitidine via intravenous or subcutaneous route. Participants randomized to the combination arm will also receive pevonedistat intravenous infusion.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 63 months. Participants will attend the end-of-treatment visit 30 days after the last dose of study drug or before the start of subsequent anti-neoplastic therapy if that occurs sooner.

Participants with HR MDS or CMML will have EFS follow-up study visits every month if their disease has not transformed to AML and they have not started subsequent therapy. Participants with low-blast AML will have response follow-up study visits every month until they relapse from CR or meet the criteria for PD. All participants will enter OS follow-up (contacted every 3 months) when they have confirmed transformation to AML (for participants with HR MDS or CMML at enrollment) or experienced PD or relapse from CR (for participants with low-blast AML at study enrollment).

Phase : III

Stade : NA

Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or nonproliferative chronic myelomonocytic leukemia (CMML) (i.e., with white blood cell [WBC] <13,000/μL) or low-blast acute myelogenous leukemia (AML).
- Has MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):
-> Very high (>6 points).
-> High (>4.5-6 points).
-> Intermediate (>3-4.5 points): a patient determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.
- Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
- Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM) score >=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers.

Calculation of TRM score:
- 0 for (age <61 years), +2 for (age 61-70 years), +4 for (age >71 years).
- + 0 for (PS=0), +2 for (PS=1), +4 for (PS >1).
- + 0 for (platelets <50), +1 for (platelets >50).

Critères de non-inclusion : - Has previous treatment for higher-risk myelodysplastic syndromes (HR MDS) or low-blast AML with chemotherapy or other antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug.
- Has acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
- Is eligible for intensive chemotherapy and/or allogeneic stem cell transplantation. The reason a participant is not eligible for intensive chemotherapy and/or allogeneic stem cell transplantation may consist of one or more of the following factors:
-> Age >75.
-> Comorbidities.
-> Inability to tolerate intensive chemotherapy (e.g., patients with AML with 20%-30% blasts and TRM ≥4).
-> Physician decision (e.g., lack of available stem cell donor).
-> The reason a participant is not eligible should be documented in the electronic case report form (eCRF).
- Has either clinical evidence of or history of central nervous system involvement by AML.
- Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
- Is diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease.
- Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
- Has prothrombin time (PT) or aPTT >1.5× upper limit of normal (ULN) or active uncontrolled coagulopathy or bleeding disorder. Participants therapeutically anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors, or heparin are excluded from enrollment.
- Has known human immunodeficiency virus (HIV) seropositive.
- Has known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.
- Has known hepatic cirrhosis or severe preexisting hepatic impairment.
- Has known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), and/or myocardial infarction within 6 months before first dose, or severe pulmonary hypertension.
- Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the first dose of pevonedistat.
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Institut d'Hématologie Bas-Normand (IHBN) - Avenue de la Cote de Nacre - 14000 CAEN

Investigateur :
Stéphane CHEZE

Véronique ABONNET

Statut de l'essai : CLOS

MAJ : 13/01/2021