Combination Chemotherapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Patients With Acute Myelogenous Leukemia
- Conditions
- Leukemia
- Registration Number
- NCT00002549
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1520
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (75)
Hospitais da Universidade de Coimbra (HUC)
🇵🇹Coimbra, Portugal
Institute of Hematology and Blood Transfusion
🇨🇿Prague, Czech Republic
Algemeen Ziekenhuis Middelheim
🇧🇪Antwerp, Belgium
A.Z. St. Jan
🇧🇪Brugge, Belgium
Institut Jules Bordet
🇧🇪Brussels (Bruxelles), Belgium
Ospedale San Eugenio
🇮🇹Rome, Italy
Ospedale Civile Alessandria
🇮🇹Alessandria, Italy
County Hospital
ðŸ‡ðŸ‡ºKecskemet, Hungary
Ospedale Regionale A. Di Summa
🇮🇹Brindisi, Italy
Ospedale Oncologico A. Businco
🇮🇹Cagliari, Italy
Universita Degli Studi di Firenze - Policlin. di Careggi
🇮🇹Firenze (Florence), Italy
Ospedale Maggiore Lodi
🇮🇹Lodi, Italy
Instituto Scientifico H.S. Raffaele
🇮🇹Milano (Milan), Italy
Universita di Modena
🇮🇹Modena, Italy
Azienda Ospedaliera "A. Cardarelli"
🇮🇹Naples (Napoli), Italy
Federico II University Medical School
🇮🇹Naples (Napoli), Italy
Ospedale Nuovo Pellegrini
🇮🇹Naples (Napoli), Italy
Azienda Ospedale S. Luigi - Universita Di Torino
🇮🇹Orbassano, (Torino), Italy
Policlinico - Cattedra di Ematologia
🇮🇹Palermo, Italy
Ospedale Civile Pescara
🇮🇹Pescara, Italy
Azienda Ospedaliera Ospedale E. Mortelli
🇮🇹Sondalo (so), Italy
Azienda Ospedaliera Di Parma
🇮🇹Parma, Italy
Ospedale San Salvatore
🇮🇹Pesaro, Italy
Ospedale San Carlo
🇮🇹Potenza, Italy
Ospedali Riuniti
🇮🇹Reggio Calabria, Italy
Arcispedale S. Maria Nuova
🇮🇹Reggio Emilia, Italy
Ospedal SS Annunziata
🇮🇹Taranto, Italy
Groot Ziekengasthuis 's-Hertogenbosch
🇳🇱's-Hertogenbosch, Netherlands
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Istituto di Ematologia Universita - University di Sassari
🇮🇹Sassari, Italy
Ospedale Molinette
🇮🇹Turin (Torino), Italy
Hospital Escolar San Joao
🇵🇹Porto, Portugal
Medisch Spectrum Twente
🇳🇱Enschede, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Ibn-i Sina Hospital, Ankara Univeristy
🇹🇷Ankara, Turkey
Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni - Rotondo, Italy
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
University Medical Center Nijmegen
🇳🇱Nijmegen, Netherlands
Sint Joseph Ziekenhuis
🇳🇱Veldhoven, Netherlands
Hotel Dieu de Paris
🇫🇷Paris, France
Universitaetsklinik
🇦🇹Innsbruck, Austria
Hopital Universitaire Erasme
🇧🇪Brussels, Belgium
University Hospital - Olomouc
🇨🇿Olomouc, Czech Republic
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
CHU Sart-Tilman
🇧🇪Liege, Belgium
Medical School/University of Zagreb
ðŸ‡ðŸ‡·Zagreb (Agram), Croatia
University Hospital Rebro
ðŸ‡ðŸ‡·Zagreb, Croatia
Centre Antoine Lacassagne
🇫🇷Nice, France
Hopital Edouard Herriot
🇫🇷Lyon, France
Hopital Necker
🇫🇷Paris, France
Centre Medico-Chirurgical Foch
🇫🇷Suresnes, France
Hopital Cochin
🇫🇷Paris, France
Klinikum Grosshadern
🇩🇪Munich (Muenchen), Germany
Institut Gustave Roussy
🇫🇷Villejuif, France
Staedtische Kliniken Duisburg
🇩🇪Duisburg, Germany
Ospedale Ferrarotto
🇮🇹Catania, Italy
Ospedale Torrette University Ancona
🇮🇹Ancona, Italy
Universita Degli Studi di Bari Policlinico
🇮🇹Bari, Italy
Ospedale Civile Avellino
🇮🇹Avellino, Italy
Ospedale Santa Croce
🇮🇹Cuneo, Italy
Centro Trapianti di Midollo Osseo
🇮🇹Cremona, Italy
Ospedali Riuniti Foggia
🇮🇹Foggia, Italy
Ospedale Regionale A. Pugliese
🇮🇹Catanzaro, Italy
Ospedale S. Antonio Abate
🇮🇹Gallarate Varese, Italy
Ospedale San Martino/Cliniche Universitarie Convenzionale
🇮🇹Genoa (Genova), Italy
Ospedale Gen. Provinciale Santa Maria Goretti
🇮🇹Latina, Italy
Ospedale Maggiore Ca Granda
🇮🇹Milano (Milan), Italy
Ospedale S. Gennora USL 42
🇮🇹Naples (Napoli), Italy
Ospedale Maggiore
🇮🇹Novara, Italy
Ospedale San Francesco
🇮🇹Nuoro, Italy
Ospedale Cervello
🇮🇹Palermo, Italy
Policlinico Monteluce
🇮🇹Perugia, Italy
Policlinico P. Giaccone - Universita Di Palermo
🇮🇹Palermo, Italy
University and I.R.C.C.S. Policlinico San Matteo
🇮🇹Pavia, Italy
Azienda Policlinico Umberto Primo
🇮🇹Rome, Italy