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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2009 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002549
First received: November 1, 1999
Last updated: December 22, 2009
Last verified: December 2009
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 1520
Study Start Date: November 1993
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.

  Eligibility

Ages Eligible for Study:   15 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002549

  Hide Study Locations
Locations
Austria
Universitaetsklinik
Innsbruck, Austria, A-6020
Belgium
Algemeen Ziekenhuis Middelheim
Antwerp, Belgium, 2020
A.Z. St. Jan
Brugge, Belgium, 8000
Hopital Universitaire Erasme
Brussels, Belgium, 1070
Institut Jules Bordet
Brussels (Bruxelles), Belgium, 1000
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
CHU Sart-Tilman
Liege, Belgium, B-4000
Croatia
University Hospital Rebro
Zagreb, Croatia, 41000
Medical School/University of Zagreb
Zagreb (Agram), Croatia, 41000
Czech Republic
University Hospital - Olomouc
Olomouc, Czech Republic, 775 20
Institute of Hematology and Blood Transfusion
Prague, Czech Republic, 128 20
France
Hopital Edouard Herriot
Lyon, France, 69437
Centre Antoine Lacassagne
Nice, France, 06189
Hopital Cochin
Paris, France, 75674
Hotel Dieu de Paris
Paris, France, 75181
Hopital Necker
Paris, France, 75743
Centre Medico-Chirurgical Foch
Suresnes, France, 92151
Institut Gustave Roussy
Villejuif, France, F-94805
Germany
Staedtische Kliniken Duisburg
Duisburg, Germany, D-47055
Klinikum Grosshadern
Munich (Muenchen), Germany, D-81377
Hungary
County Hospital
Kecskemet, Hungary, H-6000
Italy
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
Ospedale Maggiore Ca Granda
Milano (Milan), Italy, 20162
Instituto Scientifico H.S. Raffaele
Milano (Milan), Italy, 20132
Universita di Modena
Modena, Italy, 41100
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
Azienda Ospedaliera "A. Cardarelli"
Naples (Napoli), Italy, 80127
Ospedale Maggiore
Novara, Italy, 28100
Ospedale San Francesco
Nuoro, Italy, 08100
Azienda Ospedale S. Luigi - Universita Di Torino
Orbassano, (Torino), Italy, 10043
Policlinico P. Giaccone - Universita Di Palermo
Palermo, Italy, 90127
Ospedale Cervello
Palermo, Italy, 90146
Policlinico - Cattedra di Ematologia
Palermo, Italy, 90100
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
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, Italy, 00168
Ospedale San Eugenio
Rome, Italy, 00144
Azienda Policlinico Umberto Primo
Rome, Italy, 00161
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
Netherlands
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
Portugal
Hospitais da Universidade de Coimbra (HUC)
Coimbra, Portugal, 3049
Hospital Escolar San Joao
Porto, Portugal, 4200
Turkey
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
  More Information

Additional Information:
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.

ClinicalTrials.gov Identifier: NCT00002549     History of Changes
Other Study ID Numbers: CDR0000063311, EORTC-06931
Study First Received: November 1, 1999
Last Updated: December 22, 2009
Health Authority: United States: Federal Government

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:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Daunorubicin
Mitoxantrone
Alkylating Agents
Analgesics
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014