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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00002549
• Other study ID #: CDR0000063311
• Secondary ID: EORTC-06931
• Status: Active, not recruiting
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: December 22, 2009
• Start date: November 1993

Study information

• Verified date: December 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1520
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 60 Years

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• filgrastim

Drug:
• busulfan

• cyclophosphamide

• cytarabine

• daunorubicin hydrochloride

• etoposide

• idarubicin

• mesna

• mitoxantrone hydrochloride

Procedure:
• allogeneic bone marrow transplantation

• autologous bone marrow transplantation

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Austria	Universitaetsklinik	Innsbruck
Belgium	Algemeen Ziekenhuis Middelheim	Antwerp
Belgium	A.Z. St. Jan	Brugge
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels (Bruxelles)
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	CHU Sart-Tilman	Liege
Croatia	University Hospital Rebro	Zagreb
Croatia	Medical School/University of Zagreb	Zagreb (Agram)
Czech Republic	University Hospital - Olomouc	Olomouc
Czech Republic	Institute of Hematology and Blood Transfusion	Prague
France	Hopital Edouard Herriot	Lyon
France	Centre Antoine Lacassagne	Nice
France	Hopital Cochin	Paris
France	Hopital Necker	Paris
France	Hotel Dieu de Paris	Paris
France	Centre Medico-Chirurgical Foch	Suresnes
France	Institut Gustave Roussy	Villejuif
Germany	Staedtische Kliniken Duisburg	Duisburg
Germany	Klinikum Grosshadern	Munich (Muenchen)
Hungary	County Hospital	Kecskemet
Italy	Ospedale Civile Alessandria	Alessandria
Italy	Ospedale Torrette University Ancona	Ancona
Italy	Ospedale Civile Avellino	Avellino
Italy	Universita Degli Studi di Bari Policlinico	Bari
Italy	Ospedale Regionale A. Di Summa	Brindisi
Italy	Ospedale Oncologico A. Businco	Cagliari
Italy	Ospedale Ferrarotto	Catania
Italy	Ospedale Regionale A. Pugliese	Catanzaro
Italy	Centro Trapianti di Midollo Osseo	Cremona
Italy	Ospedale Santa Croce	Cuneo
Italy	Universita Degli Studi di Firenze - Policlin. di Careggi	Firenze (Florence)
Italy	Ospedali Riuniti Foggia	Foggia
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 Lodi	Lodi
Italy	Instituto Scientifico H.S. Raffaele	Milano (Milan)
Italy	Ospedale Maggiore Ca Granda	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	Ospedale S. Gennora USL 42	Naples (Napoli)
Italy	Ospedale Maggiore	Novara
Italy	Ospedale San Francesco	Nuoro
Italy	Azienda Ospedale S. Luigi - Universita Di Torino	Orbassano, (Torino)
Italy	Ospedale Cervello	Palermo
Italy	Policlinico - Cattedra di Ematologia	Palermo
Italy	Policlinico P. Giaccone - Universita Di Palermo	Palermo
Italy	Azienda Ospedaliera Di Parma	Parma
Italy	University and I.R.C.C.S. Policlinico San Matteo	Pavia
Italy	Policlinico Monteluce	Perugia
Italy	Ospedale San Salvatore	Pesaro
Italy	Ospedale Civile Pescara	Pescara
Italy	Ospedale San Carlo	Potenza
Italy	Ospedali Riuniti	Reggio Calabria
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	Azienda Policlinico Umberto Primo	Rome
Italy	Ospedale San Eugenio	Rome
Italy	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni - Rotondo
Italy	Istituto di Ematologia Universita - University di Sassari	Sassari
Italy	Azienda Ospedaliera Ospedale E. Mortelli	Sondalo (so)
Italy	Ospedal SS Annunziata	Taranto
Italy	Ospedale Molinette	Turin (Torino)
Netherlands	Groot Ziekengasthuis 's-Hertogenbosch	's-Hertogenbosch
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Leiden University Medical Center	Leiden
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Sint Joseph Ziekenhuis	Veldhoven
Portugal	Hospitais da Universidade de Coimbra (HUC)	Coimbra
Portugal	Hospital Escolar San Joao	Porto
Turkey	Ibn-i Sina Hospital, Ankara Univeristy	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  Croatia,  Czech Republic,  France,  Germany,  Hungary,  Italy,  Netherlands,  Portugal,  Turkey, 

References & Publications (3)

Mandelli F, Vignetti M, Suciu S, Stasi R, Petti MC, Meloni G, Muus P, Marmont F, Marie JP, Labar B, Thomas X, Di Raimondo F, Willemze R, Liso V, Ferrara F, Baila L, Fazi P, Zittoun R, Amadori S, de Witte T. Daunorubicin versus mitoxantrone versus idarubic — View Citation

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.