CPX-351 vs Intensive Chemotherapy in Patients With de Novo Intermediate or Adverse Risk AML Stratified by Genomics
NCT ID: NCT05260528
Last Updated: 2024-01-30
Study Results
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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RECRUITING
PHASE2
210 participants
INTERVENTIONAL
2023-05-03
2027-10-31
Brief Summary
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Detailed Description
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Interestingly comparing de novo and stringently defined secondary AMLs occurring after a documented phase of MDS, Lindsley et al. could identify among de novo AMLs a molecular subgroup, termed 'secondary-type AML', defined by mutations in either SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR and/or STAG2 genes. Among de novo AML patients, 33.3% had secondary-type mutations.
It has been shown that patients older than 60 years of age harboring secondary-type AML, as defined by this 8-gene molecular signature, had inferior outcome to those without 'secondary-type' mutations when treated with conventional 7+3 chemotherapy, combining cytarabine and an anthracycline (ALFA 1200 study). This was notably true among patients with 'intermediate-risk' disease per European LeukemiaNet criteria.
The incidence of 'secondary-type' AML mutations increases with age and with cytogenetic risk category. Notably, roughly 50% of de novo AML patients with intermediate risk older than 50 years of age harbor such secondary-type mutations, New therapeutic options are thus necessary in patients older than 50 years with de novo AML classified adverse risk but also intermediate risk and associated to secondary-type mutation
This study will evaluate the rate of MRD negative remissions with CPX-351 used as induction and consolidation therapy according to its marketing authorization (AMM), as compared to intensive chemotherapy in a population of non-MRC AMLs enriched in secondary-like mutations. In addition,P-gp activity will be explore as a putative biomarker.
Duration of the enrollment period: 36 months Duration of treatment: 6 months Duration of the participation for a patient: 18 months (post randomization) (including approximately 6 months treatment, and 12 months of post-treatment follow up) Overall duration of the study: 58 months including the analysis of the results
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Standard arm
Cytarabine and Idarubicin
Induction 1: Cytarabine 200 mg/m2 i.v. (continuously) d1-7 + Idarubicin 12mg/m2 d1, 2, 3 i.v (60 min)
Induction 2: Cytarabine 1500 mg/m2 i.v. q12h d1-3
Consolidation: Cytarabine 1500 mg/m2 i.v. q12h d1-3
Investigational arm
CPX-315
Induction 1:CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine i.v. (90 min) d1,3,5
Induction 2: CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine i.v. (90 min) d1,3
Consolidation therapy:CPX-351 29 mg/m2 daunorubicin / 65 mg/m2 cytarabine i.v. (90 min) d1,3
Interventions
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Cytarabine and Idarubicin
Induction 1: Cytarabine 200 mg/m2 i.v. (continuously) d1-7 + Idarubicin 12mg/m2 d1, 2, 3 i.v (60 min)
Induction 2: Cytarabine 1500 mg/m2 i.v. q12h d1-3
Consolidation: Cytarabine 1500 mg/m2 i.v. q12h d1-3
CPX-315
Induction 1:CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine i.v. (90 min) d1,3,5
Induction 2: CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine i.v. (90 min) d1,3
Consolidation therapy:CPX-351 29 mg/m2 daunorubicin / 65 mg/m2 cytarabine i.v. (90 min) d1,3
Eligibility Criteria
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Inclusion Criteria
2. No MRC-defining cytogenetic lesion
3. No t(15;17), t(8;21), inv(16) or t(16;16)
4. No NPM1 gene mutation
5. No FLT3 mutated AML (FLT3 ITD or TKD)
6. Not previously treated except for short course hydroxyurea in patients presenting with high WBC count and/or tumor symptoms,
7. Age ≥ 50 years,
8. Performance status ≤ 2 (ECOG grading),
9. Patient must have adequate organ function as indicated detailed with laboratory values in the section IV of the protocol
10. Female patient of childbearing potential with a negative serum pregnancy test (β-hCG) within 72 hours prior to receiving the first dose of CPX-351 or 7+3. Female patient who is not actively breastfeeding at the time of study entry.
11. Female patient is either post-menopausal, free from menses for \> 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy, or agrees to not become pregnant throughout the study, starting with study screening
12. Male patient agrees to use an adequate method of contraception for the duration of the study. Men should be advised not to father a child while receiving CPX-351 or 7+3 and for 3 months after the last dose of study treatment .
13. Patient is available for periodic blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study.
14. Patient has the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study.
15. Patient registered to the French Social Security.
Exclusion Criteria
2. Prior history of radiation therapy or chemotherapy for a solid tumor or lymphoma (exceptions to be considered: local radiotherapy for prostate cancer)
3. Patient has active and uncontrolled infection.
4. Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including but not limited to the following: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, or psychiatric or social conditions that may interfere with patient compliance.
5. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug.
6. Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
7. Patient has clinically active hepatitis B or hepatitis C infection.
8. Patient has a known allergy or hypersensitivity to any component of CPX-351, idarubicin or cytarabine.
9. Patient with a "currently active" second malignancy, other than nonmelanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for \>1 year or are considered by their physician to be at less than 30% risk of relapse.
10. Patients with clinical evidence of CNS leukemia.
11. Cardiac ejection fraction \<50% or considered as abnormal by echocardiography or multi-gated acquisition (MUGA) scan.
12. Patient is pregnant or breastfeeding within the projected duration of the study.
18 Years
ALL
No
Sponsors
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Jazz Pharmaceuticals
INDUSTRY
Acute Leukemia French Association
OTHER
Centre Hospitalier Universitaire de Nice
OTHER
Responsible Party
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Locations
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CHU Amiens Picardie site Sud
Amiens, , France
CH Avignon
Avignon, , France
CHRU Jean Minjoz
Besançon, , France
Centre Hospitalier de Béziers
Béziers, , France
Hôpital Avicenne APHP
Bobigny, , France
Institut d'hématologie de Basse Normandie (IHBN)
Caen, , France
Hôpital d'Instruction des Armée (HIA)
Clamart, , France
CHU Estaing
Clermont-Ferrand, , France
Centre Hospitalier Sud Francilien (CHSF)
Corbeil-Essonnes, , France
CHU Henri Mondor
Créteil, , France
Centre Hospitalier de Versailles, Site André Mignot
Le Chesnay, , France
Hôpital Claude HURIEZ, CHU Lille
Lille, , France
CHU de Limoges
Limoges, , France
Hoptial de la Conception APHM
Marseille, , France
CHR Metz-Thionville Site Mercy
Metz, , France
Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Hôpital Emile Muller
Mulhouse, , France
Centre Antoine Lacassagne
Nice, , France
CHU de Nice
Nice, , France
Institut de cancérologie du Gard
Nîmes, , France
CHR Orléans
Orléans, , France
Hopital Necker
Paris, , France
Hôpital de la Pitié Salpêtrière
Paris, , France
Hôpital Saint-Antoine
Paris, , France
Hôpital Saint-Louis
Paris, , France
Hopital Lyon Sud
Pierre-Bénite, , France
CH de Roubaix
Roubaix, , France
Centre Henri Becquerel
Rouen, , France
CHU de Saint Etienne
Saint-Priest-en-Jarez, , France
Hopital Bretonneau
Tours, , France
Institut Gustave Roussy
Villejuif, , France
Countries
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Central Contacts
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Facility Contacts
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Delphine Lebon
Role: primary
Safia Chebrek
Role: primary
Yohan Desbrosses
Role: primary
Alain Saad
Role: primary
Thorsten Braun
Role: primary
Sylvain Chantepie
Role: primary
Pierre Arnautou
Role: primary
Romain Guieze
Role: primary
Stéphanie Haiat
Role: primary
Cécile Pautas
Role: primary
Juliette Lambert
Role: primary
Celine Berthon
Role: primary
Pascal Turlure
Role: primary
Regis Costello
Role: primary
Houria Debarri
Role: primary
Mario Ojeda-Uribe
Role: primary
Lauris Gastaud
Role: primary
Thomas Cluzeau, MD
Role: primary
Samy Chraibi
Role: primary
Diana Carp
Role: primary
Ambroise Marcais
Role: primary
Madalina Uzunov
Role: primary
Ollivier Legrand
Role: primary
Florence Rabian
Role: primary
Mael Heiblig
Role: primary
Isabelle Plantier
Role: primary
Emilie Lemasle-Hue
Role: primary
Emmanuelle Tavernier
Role: primary
Alban Villate
Role: primary
Sephane De Botton
Role: primary
Other Identifiers
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21-PP-26
Identifier Type: -
Identifier Source: org_study_id
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