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

Sponsor
European Organisation for Research and Treatment of Cancer - EORTC (Other)
Overall Status
Unknown status
CT.gov ID
NCT00002549
Collaborator
(none)
1,520
75
20.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

  1. 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 Design

Study Type:
Interventional
Anticipated Enrollment :
1520 participants
Allocation:
Randomized
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Nov 1, 1993

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    15 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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)

    Contacts and Locations

    Locations

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

    Sponsors and Collaborators

    • European Organisation for Research and Treatment of Cancer - EORTC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00002549
    Other Study ID Numbers:
    • CDR0000063311
    • EORTC-06931
    First Posted:
    Jul 19, 2004
    Last Update Posted:
    Dec 23, 2009
    Last Verified:
    Dec 1, 2009

    Study Results

    No Results Posted as of Dec 23, 2009