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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002549
Recruitment Status : Unknown
Verified December 2009 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : July 19, 2004
Last Update Posted : December 23, 2009
Information provided by:
National Cancer Institute (NCI)

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
Leukemia Biological: filgrastim Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: idarubicin Drug: mesna Drug: mitoxantrone hydrochloride Procedure: allogeneic bone marrow transplantation Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy 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. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1520 participants
Allocation: Randomized
Primary Purpose: Treatment
Study Start Date : November 1993

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002549

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

Publications of Results:
Other Publications:
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.

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00002549     History of Changes
Other Study ID Numbers: CDR0000063311
First Posted: July 19, 2004    Key Record Dates
Last Update Posted: December 23, 2009
Last Verified: December 2009
Keywords provided by National Cancer Institute (NCI):
untreated adult acute myeloid leukemia
adult acute erythroid leukemia (M6)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute megakaryoblastic leukemia (M7)
secondary acute myeloid leukemia
adult acute monocytic leukemia (M5b)
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic