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Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Acute Myelogenous Leukemia

22 décembre 2009 mis à jour par: European Organisation for Research and Treatment of Cancer - EORTC

RANDOMIZED PHASE III STUDY OF INDUCTION (ICE VS MICE VS DCE) AND INTENSIVE CONSOLIDATION (IDIA VS NOVIA VS DIA) FOLLOWED BY BONE MARROW TRANSPLANTATION IN ACUTE MYELOGENOUS LEUKEMIA: AML 10 PROTOCOL

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell or bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy followed by bone marrow or peripheral stem cell transplantation in treating patients with acute myelogenous leukemia.

Aperçu de l'étude

Statut

Inconnue

Les conditions

Leucémie

Intervention / Traitement

Description détaillée

OBJECTIVES: I. Determine the complete remission (CR) rate following 1 or 2 courses of ICE (idarubicin/cytarabine/etoposide) vs. MICE (mitoxantrone/cytarabine/etoposide) vs. DCE (daunorubicin/cytarabine/etoposide) in patients with newly diagnosed acute myeloid leukemia. II. Compare disease-free survival and overall survival achieved with each anthracycline on the above induction regimens and with intermediate-dose cytarabine (IDIA vs. NOVIA vs. DIA) as consolidation therapy. III. Compare disease-free survival, relapse rate, death in first CR, and overall survival in patients who receive peripheral blood stem cells (PBSC) vs. autologous bone marrow transplant (AuBMT) vs. allogeneic bone marrow transplant (AlBMT) as rescue from myeloablative therapy following remission consolidation. IV. Assess the time to recovery of normal or acceptable polymorphonuclear leukocyte and platelet counts following each treatment step. V. Determine the incidence and type of grade 4 toxicity and treatment-related mortality. VI. Evaluate the quality of life during each step of treatment using self-administered questionnaires. VII. Compare stem cell mobilization after IDIA vs. NOVIA vs. DIA, each using granulocyte colony-stimulating factor as the mobilizing growth factor. VIII. Assess the rate of completion of stem cell transplantation using PBSC vs. AlBMT vs. AuBMT as the last step of therapy. IX. Compare the costs of treatment (e.g., antibiotics and transfusion requirements) and hospitalization duration between the AuBMT vs. PBSC.

OUTLINE: Randomized study. All patients are randomized to Arms I, II, and III for Induction/Consolidation. Patients in CR following Consolidation who have an HLA-identical sibling, are less than 45 or 55 years of age (depending on center policy), and have adequate organ function are nonrandomly assigned to AlBMT on Regimen A; those in CR who are without an available sibling donor and who have adequate organ function proceed to Regimen B, then are randomized to Arms IV and V. The following acronyms are used: AlBMT Allogeneic Bone Marrow Transplant ARA-C Cytarabine, NSC-63878 AuBMT Autologous Bone Marrow Transplant BU Busulfan, NSC-750 CTX Cyclophosphamide, NSC-26271 DCE DNR/ARA-C/VP-16 DHAD Mitoxantrone, NSC-301739 DIA DNR/ID ARA-C DNR Daunorubicin, NSC-82151 G-CSF Granulocyte Colony-Stimulating Factor (Rhone-Poulenc-Rorer) ICE IDA/ARA-C/VP-16 IDA Idarubicin, NSC-256439 ID Intermediate Dose IDIA IDA/ID ARA-C Mesna Mercaptoethane sulfonate, NSC-113891 MICE DHAD/ARA-C/VP-16 NOVIA DHAD/ID ARA-C PBSC Peripheral Blood Stem Cells TBI Total-Body Irradiation VP-16 Etoposide, NSC-141540 INDUCTION/CONSOLIDATION: Arm I: 3-Drug Combination Chemotherapy followed by 2-Drug Combination Chemotherapy. ICE; followed by IDIA. Arm II: 3-Drug Combination Chemotherapy followed by 2-Drug Combination Chemotherapy. MICE; followed by NOVIA. Arm III: 3-Drug Combination Chemotherapy followed by 2-Drug Combination Chemotherapy. DCE; followed by DIA. POSTCONSOLIDATION THERAPY: Regimen A: Single-Agent Chemoablation plus Radioablation or 2-Drug Chemoablation followed by Hematopoietic Rescue. CTX; plus TBI (equipment unspecified); or CTX/BU; followed by AlBMT. Entry on EORTC study comparing CI IDA with standard CTX/TBI or CTX/BU encouraged. Regimen B: Stem cell Mobilization and Harvest. G-CSF or CTX/G-CSF. Arm IV: Single-Agent Chemoablation plus Radioablation or 2-Drug Chemoablation followed by Hematopoietic Rescue. CTX/TBI or CTX/BU; followed by PBSC. Arm V: Single-Agent Chemoablation plus Radioablation or 2-Drug Chemoablation followed by Hematopoietic Rescue. CTX/TBI or CTX/BU; followed by AuBMT.

PROJECTED ACCRUAL: 1,520 patients will be randomized for Induction/Consolidation over about 5 years; if excessive deaths are found at interim analyses, the inferior arm will close. It is expected that 744 patients will be randomized for Postconsolidation therapy, with 345 patients followed until relapse/death.

Type d'étude

Interventionnel

Inscription (Anticipé)

1520

Phase

Phase 3

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

Allemagne
- - Duisburg, Allemagne, D-47055
    - Staedtische Kliniken Duisburg
  - Munich (Muenchen), Allemagne, D-81377
    - Klinikum Großhadern
Belgique
- - Antwerp, Belgique, 2020
    - Algemeen Ziekenhuis Middelheim
  - Brugge, Belgique, 8000
    - A.Z. St. Jan
  - Brussels, Belgique, 1070
    - Hopital Universitaire Erasme
  - Brussels (Bruxelles), Belgique, 1000
    - Institut Jules Bordet
  - Edegem, Belgique, B-2650
    - Universitair Ziekenhuis Antwerpen
  - Liege, Belgique, B-4000
    - CHU Sart-Tilman
Croatie
- - Zagreb, Croatie, 41000
    - University Hospital Rebro
  - Zagreb (Agram), Croatie, 41000
    - Medical School/University of Zagreb
France
- - Lyon, France, 69437
    - Hôpital Edouard Herriot
  - Nice, France, 06189
    - Centre Antoine Lacassagne
  - Paris, France, 75674
    - Hôpital Cochin
  - Paris, France, 75743
    - Hopital Necker
  - Paris, France, 75181
    - Hotel Dieu de Paris
  - Suresnes, France, 92151
    - Centre Medico-Chirurgical Foch
  - Villejuif, France, F-94805
    - Institut Gustave Roussy
Hongrie
- - Kecskemet, Hongrie, H-6000
    - County Hospital
Italie
- - Alessandria, Italie, I-15100
    - Ospedale Civile Alessandria
  - Ancona, Italie, 60020
    - Ospedale Torrette University Ancona
  - Avellino, Italie
    - Ospedale Civile Avellino
  - Bari, Italie, 70124
    - Universita Degli Studi di Bari Policlinico
  - Brindisi, Italie, I-72100
    - Ospedale Regionale A. Di Summa
  - Cagliari, Italie, 09124
    - Ospedale Oncologico A. Businco
  - Catania, Italie, 95124
    - Ospedale Ferrarotto
  - Catanzaro, Italie, 88100
    - Ospedale Regionale A. Pugliese
  - Cremona, Italie, 26100
    - Centro Trapianti di Midollo Osseo
  - Cuneo, Italie, 12100
    - Ospedale Santa Croce
  - Firenze (Florence), Italie, 1 (50-134)
    - Universita Degli Studi di Firenze - Policlin. di Careggi
  - Foggia, Italie, 71100
    - Ospedali Riuniti Foggia
  - Gallarate Varese, Italie, 21013
    - Ospedale S. Antonio Abate
  - Genoa (Genova), Italie, 16132
    - Ospedale San Martino/Cliniche Universitarie Convenzionale
  - Latina, Italie, 04100
    - Ospedale Gen. Provinciale Santa Maria Goretti
  - Lodi, Italie, I-20075
    - Ospedale Maggiore Lodi
  - Milano (Milan), Italie, 20132
    - Instituto Scientifico H.S. Raffaele
  - Milano (Milan), Italie, 20162
    - Ospedale Maggiore Ca Granda
  - Modena, Italie, 41100
    - Università di Modena
  - Naples (Napoli), Italie, 80127
    - Azienda Ospedaliera "A. Cardarelli"
  - Naples (Napoli), Italie, 80131
    - Federico II University Medical School
  - Naples (Napoli), Italie, 80136
    - Ospedale S. Gennora USL 42
  - Naples (Napoli), Italie, 80144
    - Ospedale Nuovo Pellegrini
  - Novara, Italie, 28100
    - Ospedale Maggiore
  - Nuoro, Italie, 08100
    - Ospedale San Francesco
  - Orbassano, (Torino), Italie, 10043
    - Azienda Ospedale S. Luigi - Universita Di Torino
  - Palermo, Italie, 90146
    - Ospedale Cervello
  - Palermo, Italie, 90100
    - Policlinico - Cattedra di Ematologia
  - Palermo, Italie, 90127
    - Policlinico P. Giaccone - Universita Di Palermo
  - Parma, Italie, 43100
    - Azienda Ospedaliera di Parma
  - Pavia, Italie, 27100
    - University and I.R.C.C.S. Policlinico San Matteo
  - Perugia, Italie, 06122
    - Policlinico Monteluce
  - Pesaro, Italie, I-61100
    - Ospedale San Salvatore
  - Pescara, Italie, 65100
    - Ospedale Civile Pescara
  - Potenza, Italie, 85100
    - Ospedale San Carlo
  - Reggio Calabria, Italie, 89100
    - Ospedali Riuniti
  - Reggio Emilia, Italie, 42100
    - Arcispedale S. Maria Nuova
  - Rome, Italie, 00161
    - Azienda Policlinico Umberto Primo
  - Rome, Italie, 00168
    - Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
  - Rome, Italie, 00144
    - Ospedale San Eugenio
  - San Giovanni - Rotondo, Italie, 71013
    - Ospedale Casa Sollievo della Sofferenza
  - Sassari, Italie, 07100
    - Istituto di Ematologia Universita - University di Sassari
  - Sondalo (so), Italie, 23037
    - Azienda Ospedaliera Ospedale E. Mortelli
  - Taranto, Italie, 74100
    - Ospedal SS Annunziata
  - Turin (Torino), Italie, 10126
    - Ospedale Molinette
L'Autriche
- - Innsbruck, L'Autriche, A-6020
    - Universitaetsklinik
Le Portugal
- - Coimbra, Le Portugal, 3049
    - Hospitais da Universidade de Coimbra (HUC)
  - Porto, Le Portugal, 4200
    - Hospital Escolar San Joao
Pays-Bas
- - 's-Hertogenbosch, Pays-Bas, 5211 NL
    - Groot Ziekengasthuis 's-Hertogenbosch
  - Amsterdam, Pays-Bas, 1091 HA
    - Onze Lieve Vrouwe Gasthuis
  - Enschede, Pays-Bas, 7500 KA
    - Medisch Spectrum Twente
  - Leiden, Pays-Bas, 2300 ZA
    - Leiden University Medical Center
  - Nijmegen, Pays-Bas, NL-6252 HB
    - University Medical Center Nijmegen
  - Veldhoven, Pays-Bas, 5500 MB DB
    - Sint Joseph Ziekenhuis
République tchèque
- - Olomouc, République tchèque, 775 20
    - University Hospital - Olomouc
  - Prague, République tchèque, 128 20
    - Institute of Hematology and Blood Transfusion
Turquie
- - Ankara, Turquie, 06100
    - Ibn-i Sina Hospital, Ankara Univeristy

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

15 ans à 60 ans (Enfant, Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

DISEASE CHARACTERISTICS: Newly diagnosed acute myeloid leukemia (AML) of any FAB histology (M1-M7) except M3 At least 30% blast cells in bone marrow smears Secondary leukemias eligible, as follows: Following cured malignancies, including Hodgkin's disease Following exposure to alkylating agents or radiotherapy for other reasons The following leukemias are excluded: Blast crisis of chronic myeloid leukemia Leukemia secondary to other myeloproliferative disease Leukemia secondary to myelodysplastic syndrome of more than 6 months' duration No other progressive malignant disease

PATIENT CHARACTERISTICS: Age: 15 to 60 Performance status: Not specified Hematopoietic: Not applicable Hepatic: Bilirubin no greater than 1.5 x ULN Renal: Creatinine no greater than 1.5 x ULN Cardiovascular: No severe heart failure requiring diuretics or with an LVEF less than 50% Other: No severe concomitant neurologic disease No severe concomitant psychologic disease

PRIOR CONCURRENT THERAPY: No prior therapy for AML (chemotherapy, radiotherapy, or more than 7 days of corticosteroids)

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: Randomisé

Collaborateurs et enquêteurs

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

Parrainer

European Organisation for Research and Treatment of Cancer - EORTC

Les enquêteurs

Chaise d'étude: Robert A. Zittoun, MD, Hotel Dieu de Paris

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

Maurillo L, Buccisano F, Spagnoli A, et al.: In acute myeloid leukemia, the use in induction of standard dose arac is associated with a better quality of response as compared to an induction regimen containing high dose arac. [Abstract] Blood 114 (22): A-1584, 2009.
Oosterveld, M, Suciu S, Muus P, et al.: A new prognostic disease specific model to predict survival after intensive antileukemic treatment for young patients with poor-risk MDS and AML: results of the CRIANT and AML-10 studies conducted by the EORTC/GIMEMA/SAKK/HOVON/EBMT groups. [Abstract] Blood 104 (11): A-2020, 2004.
Mandelli F, Vignetti M, Suciu S, Stasi R, Petti MC, Meloni G, Muus P, Marmont F, Marie JP, Labar B, Thomas X, Di Raimondo F, Willemze R, Liso V, Ferrara F, Baila L, Fazi P, Zittoun R, Amadori S, de Witte T. Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA Groups Study AML-10. J Clin Oncol. 2009 Nov 10;27(32):5397-403. doi: 10.1200/JCO.2008.20.6490. Epub 2009 Oct 13. Erratum In: J Clin Oncol. 2010 Mar 10;28(8):1438.
Baron F, Stevens-Kroef M, Kicinski M, Meloni G, Muus P, Marie JP, Halkes CJM, Thomas X, Vrhovac R, Albano F, Lefrere F Sr, Sica S, Mancini M, Venditti A, Hagemeijer A, Jansen JH, Amadori S, de Witte T, Willemze R, Suciu S. Impact of induction regimen and allogeneic hematopoietic cell transplantation on outcome in younger adults with acute myeloid leukemia with a monosomal karyotype. Haematologica. 2019 Jun;104(6):1168-1175. doi: 10.3324/haematol.2018.204826. Epub 2018 Dec 6.
Baron F, Stevens-Kroef M, Kicinski M, Meloni G, Muus P, Marie JP, Halkes CJM, Thomas X, Vrhovac R, Specchia G, Lefrere F Sr, Sica S, Mancini M, Venditti A, Hagemeijer A, Becker H, Jansen JH, Amadori S, de Witte T, Willemze R, Suciu S. Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15-60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials. Ann Hematol. 2018 Oct;97(10):1785-1795. doi: 10.1007/s00277-018-3396-4. Epub 2018 Jun 20.

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

1 novembre 1993

Dates d'inscription aux études

Première soumission

1 novembre 1999

Première soumission répondant aux critères de contrôle qualité

16 juillet 2004

Première publication (Estimation)

19 juillet 2004

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

23 décembre 2009

Dernière mise à jour soumise répondant aux critères de contrôle qualité

22 décembre 2009

Dernière vérification

1 décembre 2009

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

CDR0000063311
EORTC-06931

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 .