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Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia (AML1310)

3 août 2018 mis à jour par: Gruppo Italiano Malattie EMatologiche dell'Adulto

Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia. GIMEMA Protocol AML1310. EudraCT Number 2010-023809-36

The purpose of this study is to determine whether a risk-adapted, minimal-residual-disease directed therapy for young adults with newly diagnosed acute myeloid leukemia has positive results in terms of overall survival at 24 months.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

The general objective of this study is that of setting up a multicentre, risk-adapted study that relies on pre-treatment cytogenetic/genetic features and post-consolidation assessment of Minimal Residual Disease (MRD) to establish the final risk assignment and treatment of younger (≤ 60 years) patients with Acute Myeloid Leukemia (AML). Aim of this clinical trial is to verify whether the delivery of a post remission therapy whose intensity is risk-driven will improve the outcome in terms of both increased anti-leukemic efficacy and reduced therapy-related toxicity.

All patients will receive induction and consolidation chemotherapy according to the Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) LAM99P protocol. After the first consolidation, patients belonging to the low-risk category (core binding factor positive AML without c-Kit mutations, NPM1 positive FLT3 negative AML) will receive autologous stem cell transplantation, patients with high-risk features (adverse-risk karyotype, FLT3-ITD mutations), will be assigned to allogeneic stem cell transplantation. Patients with FLT3-TKD mutations or c-Kit mutated core binding factor positive AML and those belonging to the intermediate-risk karyotype category will be stratified according to MRD by flow cytometry and will receive risk-adapted treatment (autologous vs. allogeneic stem cell transplantation). All patients who meet the criteria for high-risk definition will be offered the allogeneic transplantation option regardless of the availability of a Human Leukocyte Antigen (HLA) identical sibling. In fact, for those lacking a HLA identical sibling all the other sources of hematopoietic stem cells (matched unrelated donor from international registry, unrelated cord blood, family haploidentical donor) will be considered. Autologous or allogeneic stem cell transplantation will be performed within 3 months from the end of consolidation therapy.

Type d'étude

Interventionnel

Inscription (Anticipé)

515

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Italie
      • Alessandria, Italie
        • S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
      • Ancona, Italie
        • Azienda Ospedaliera - Nuovo Ospedale "Torrette"
      • Avellino, Italie
        • Az. Ospedaliera S. G. Moscati
      • Bari, Italie, 70010
        • Unità Operativa Ematologia 1 - Università degli Studi di Bari
      • Barletta, Italie
        • UOC Ematologia Ospedale " Monsignor Raffaele Dimiccoli"
      • Bologna, Italie
        • Ist.Ematologia e Oncologia Medica L.e A. Seragnoli
      • Brindisi, Italie
        • Divisione di Ematologia Ospedale A. Perrino
      • Cagliari, Italie
        • Servizio di Ematologia - CTMO - ASL 8 P.O. Binaghi
      • Caserta, Italie
        • Unità Operativa Complessa di Onco-Ematologia - A.O. S.Anna e S.Sebastiano
      • Catania, Italie
        • Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
      • Catanzaro, Italie, 88100
        • Azienda Ospedaliera Pugliese Ciaccio
      • Civitanova, Italie
        • Marche U.O. di Medicina Interna - ASUR Marche 8 - Ospedale Civile
      • Cona, Italie
        • Azienda Ospedaliero Universitaria Arcispedale Sant'Anna Dipartimento di Scienze Mediche Sezione di Ematologia e Fisiopatologia dell'Emostasi
      • Cremona, Italie
        • Sezione di Ematologia C.T.M.O. Istituti Ospitalieri
      • Ferrara, Italie, 44100
        • Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna
      • Foggia, Italie
        • Struttura Complessa di Ematologia Ospedali Riuniti Foggia - Azienda Ospedaliero-Universitaria
      • Genova, Italie
        • Clinica Ematologica - Università degli Studi
      • Latina, Italie
        • Divisione di Ematologia Ospedale "Santa Maria Goretti"
      • Lecce, Italie
        • ASL Le/1 P.O. Vito Fazzi - U.O. di Ematol
      • Meldola, Italie
        • Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST
      • Messina, Italie
        • Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
      • Messina, Italie
        • Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte"
      • Milano, Italie
        • UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico
      • Milano, Italie
        • Ospedale Niguarda " Ca Granda"
      • Modena, Italie
        • Centro Oncologico Modenese - Dipartimento di Oncoematologia
      • Napoli, Italie
        • Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
      • Nocera Inferiore, Italie
        • Pr. Alfonso Maria D'Arco
      • Novara, Italie
        • S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro
      • Orbassano, Italie, 10043
        • Ospedale S. Luigi Gonzaga
      • Padova, Italie
        • Università degli Studi di Padova - Ematologia ed Immunologia Clinica
      • Palermo, Italie
        • Divisione di Ematologia con trapianto di midollo - A.U. Policlinico "Paolo Giaccone"
      • Palermo, Italie, 90146
        • Ospedale Riuniti "Villa-Sofia-Cervello"
      • Parma, Italie
        • Cattedra di Ematologia CTMO Università degli Studi di Parma
      • Perugia, Italie
        • Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia
      • Pesaro, Italie
        • Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore
      • Pescara, Italie, 61100
        • Azienda ASL di Pescara
      • Piacenza, Italie
        • Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza
      • Pisa, Italie
        • Università di Pisa - Azienda Ospedaliera Pisana - Dipartimento di Oncologia, dei Trapianti e delle nuove Tecnologie in Medicina - Divisione di Ematologia
      • Potenza, Italie
        • Ematologia - Ospedale San Carlo
      • Ravenna, Italie, 48100
        • Ospedale S.Maria delle Croci
      • Reggio Calabria, Italie
        • Dipartimento Emato-Oncologia A.O."Bianchi-Melacrino-Morelli"
      • Reggio Emilia, Italie
        • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova
      • Rimini, Italie
        • Ospedale "Infermi"
      • Roma, Italie
        • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
      • Roma, Italie
        • Az. Ospedaliera "Sant' Andrea"-Università la Sapienza Seconda Facoltà di Medicina e Chirurgia
      • Roma, Italie
        • S.C. di Ematologia e Trapianti - I.F.O. Istituto Nazionale Tumori Regina Elena
      • Roma, Italie, 00168
        • Università Cattolica del Sacro Cuore - Policlinico A. Gemelli
      • Roma, Italie, 00128
        • Divisione Ematologia - Università Campus Bio-Medico
      • Rome, Italie
        • U.O.C. Ematologia - Ospedale S.Eugenio
      • Rome, Italie
        • Ospedale S. Camillo
      • Rozzano, Italie
        • Sezione di Ematologia Cancer Center Humanitas
      • San Giovanni Rotondo, Italie
        • Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza
      • Sassari, Italie
        • Serv. di Ematologia Ist. di Ematologia ed Endocrinologia
      • Siena, Italie
        • U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
      • Taormina, Italie
        • UOC di Ematologia Generale P.O. S.Vincenzo
      • Taranto, Italie
        • U.O.C. di Ematolgia - A.O. " SS Annunziata" - P.O. S.G. Moscati
      • Treviso, Italie
        • Azienda U.L.S.S.9 - U.O. di Ematologia
      • Udine, Italie, 33100
        • Policlinico Universitario - Clinica Ematologia
    • (le)
      • Tricase, (le), Italie
        • U.O. di Ematologia - Azienda Ospedaliera - Pia Fondazione di Culto e di Religione Card. G.Panico
    • (rm)
      • Roma, (rm), Italie, 00184
        • Complesso Ospedaliero S. Giovanni Addolorata
      • Rome, (rm), Italie, 00133
        • Policlinico di Tor Vergata

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 60 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Signed written informed consent according to ICH/EU/GCP and national/local laws
  • Patients aged between 18 and 60 years
  • Patients previously untreated for their AML by other chemotherapeutic agents (with the exception of no more than 7 days hydroxyurea (HU)), radiotherapy or more than 7 days corticosteroids
  • Unequivocal diagnosis of untreated de novo AML according to WHO diagnostic criteria (at least 20% blasts in the bone marrow), with FAB classification other than M3 (acute promyelocytic leukemia), documented by bone marrow aspiration (or biopsy in case of dry tap) (not supervening after other myeloproliferative disease or myelodysplastic syndromes of more than 6 months duration)
  • WHO performance status 0-3
  • Adequate renal (serum creatinine < 2 x the institutional Upper Limit of Normal (ULN)) and liver (total serum bilirubin < 2 x ULN; serum ALT and AST ≤ 3 x ULN) function, unless considered due to organ leukemic involvement
  • Left Ventricular Ejection Fraction (LVEF) >50%, as determined by echocardiogram
  • Absence of severe concomitant neurological or psychiatric diseases and congestive heart failure or active uncontrolled infection
  • Absence of any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and the follow-up schedule.

Exclusion Criteria:

  • Patients aged less than 18 or more than 60 years
  • Patients already treated for their AML by other chemotherapeutic agents (with the exception of no more than 7 days HU), radiotherapy or more than 7 days corticosteroids
  • Acute promyelocytic leukaemia
  • Blast crisis of chronic myeloid leukaemia
  • AML supervening after other myeloproliferative disease
  • AML supervening after antecedent myelodysplastic syndromes of more than 6 months duration
  • Other progressive malignant diseases. However, secondary AML following previously cured malignancies may be included as well as secondary AML following previous exposure to alkylating agents or radiation for other reason
  • Inadequate renal or liver function (metabolic abnormalities > 3 times the normal upper limit)
  • Severe heart failure requiring diuretics
  • Ejection fraction < 50%
  • Uncontrolled infections
  • WHO performance status = 4
  • Severe concomitant neurological or psychiatric diseases
  • Patients who are pregnant or 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 chemotherapy. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: MRD-directed therapy
Autre: Risk-adapted, MRD-directed therapy
The general objective of this study is that of setting up a multicentre, risk-adapted study that relies on pre-treatment cytogenetic/genetic features and post-consolidation assessment of MRD to establish the final risk assignment and treatment of younger (≤ 60 years) patients with AML. Aim of this clinical trial is to verify whether the delivery of a post remission therapy whose intensity is risk-driven will improve the outcome in terms of both increased anti-leukemic efficacy and reduced therapy-related toxicity.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Treatment strategy in terms of Overall Survival (OS) at 24 months.
Délai: 24 months from study entry.
OS is defined as the time interval between the date of study entry and death for any cause; patients still alive will be censored at the time of the last follow-up.
24 months from study entry.

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Estimation of Disease Free Survival (DFS) from Complete Response (CR) evaluation.
Délai: At 24 months from study entry
DFS is defined as the time interval between the evaluation of CR -after induction phase- and relapse or death in CR; patients still alive, in first CR, will be censored at the time of the last follow-up.
At 24 months from study entry
Estimation of Event Free Survival (EFS) from study entry.
Délai: at 24 months from study entry
EFS is defined as the time interval between the date of study entry dose and failure during induction phase, relapse or death whichever comes first; patients still alive, in first CR, will be censored at the time of the last follow-up.
at 24 months from study entry
Rate of patients in CR after induction therapy
Délai: At 31 days from study entry if pts are in CR or at 69 days from study entry if pts are in PR after 1 induction cycle
At 31 days from study entry if pts are in CR or at 69 days from study entry if pts are in PR after 1 induction cycle
Toxicity according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
Délai: From study entry to study completion (6 months therapy + 18 months follow-up)
From study entry to study completion (6 months therapy + 18 months follow-up)
Estimation of OS, EFS, DFS and Cumulative Incidence of Relapse (CIR) according to risk groups (Low, Intermediate, High)
Délai: At 24 months from study entry
CIR is calculated from the date of achievement of the CR -after induction phase-, using the cumulative incidence method, considering death in CR as a competing risk. Patients still alive, without relapse, will be censored at the time of the last follow-up.
At 24 months from study entry
Estimation of OS, EFS, DFS and CIR according to the Minimal Residual Disease (MRD) level at each evaluation step
Délai: At 24 months from study entry
At 24 months from study entry
Rate of CR patients and estimation OS, EFS, DFS and CIR according to baseline characteristics such as age, performance status, white blood cell (WBC), morphology, cytogenetic and molecular features.
Délai: At 24 months from study entry
At 24 months from study entry
Quality of Life evaluation
Délai: Before treatment starts, after induction, at one year after baseline evaluation.

QoL should be measured at three different time points:

  1. At Baseline (before treatment starts).
  2. At the end of Induction phase (after evaluation of response and before start of consolidation therapy for patients in CR or salvage therapy for patients not achieving a CR).
  3. At one year after baseline evaluation.
Before treatment starts, after induction, at one year after baseline evaluation.

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Gruppo Italiano Malattie EMatologiche dell'Adulto

Les enquêteurs

  • Chercheur principal: Adriano VENDITTI, Pr., Policlinico Tor Vergata di Roma

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 janvier 2012

Achèvement primaire (Réel)

1 juillet 2017

Achèvement de l'étude (Réel)

10 juillet 2018

Dates d'inscription aux études

Première soumission

12 octobre 2011

Première soumission répondant aux critères de contrôle qualité

14 octobre 2011

Première publication (Estimation)

17 octobre 2011

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

6 août 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

3 août 2018

Dernière vérification

1 août 2018

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • AML1310

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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