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

December 22, 2009 updated by: 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

1520

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Robert A. Zittoun, MD, Hotel Dieu de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 1993

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

July 16, 2004

First Posted (Estimate)

July 19, 2004

Study Record Updates

Last Update Posted (Estimate)

December 23, 2009

Last Update Submitted That Met QC Criteria

December 22, 2009

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000063311
  • EORTC-06931

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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