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Chemotherapy With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia (AML-17)

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ClinicalTrials.gov Identifier: NCT00052299
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : August 27, 2012
Sponsor:
Collaborator:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combining combination chemotherapy with monoclonal antibody therapy will kill more cancer cells.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy with or without gemtuzumab ozogamicin in treating patients who have acute myeloid leukemia.


Condition or disease Intervention/treatment Phase
Leukemia Drug: cytarabine Drug: etoposide Drug: gemtuzumab ozogamicin Drug: idarubicin Drug: mitoxantrone hydrochloride Phase 3

Detailed Description:

OBJECTIVES:

  • Determine the antileukemic activity of standard induction chemotherapy with or without gemtuzumab ozogamicin in elderly patients with previously untreated acute myeloid leukemia.
  • Determine the overall survival of patients treated with these regimens.
  • Determine the rate of response, disease-free survival, event-free survival, incidence of relapse, and incidence of death of patients treated with these regimens.
  • Determine the rate, type, and grade of toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to age (61-69 vs 70-75), CD33 positivity (less than 5% vs 5-19% vs 20-80% vs more than 80% vs unknown), initial WBC before hydroxyurea administration if needed (less than 30,000/mm^3 vs at least 30,000/mm^3), and participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I:

    • Induction (phase I): Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15.
    • Induction (phase II/MICE regimen): Beginning between days 50 and 53, patients receive mitoxantrone IV over 30 minutes on days 1, 3, and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-7. Bone marrow evaluation is performed on day 29. Patients with partial remission (PR) receive a second course of MICE chemotherapy regimen. Patients with complete remission (CR) after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients with progressive disease go off therapy.
    • Consolidation: Beginning within 4 weeks of documentation of CR, patients receive gemtuzumab ozogamicin IV over 2 hours on day 0; idarubicin IV on days 1, 3, and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-5. After at least day 30, patients receive a second consolidation course in the absence of disease progression or unacceptable toxicity.
  • Arm II:

    • Induction (MICE regimen): Patients receive mitoxantrone, etoposide, and cytarabine as in arm I induction. Bone marrow evaluation is performed on day 29. Patients with PR receive a second course of MICE chemotherapy regimen. Patients with CR after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients with progressive disease go off therapy.
    • Consolidation: Patients receive idarubicin, etoposide, and cytarabine as in arm I consolidation.

Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this study within 3.75 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 472 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Gemtuzumab Ozogamicin (GO) Combined With Standard Intensive Chemotherapy Versus Standard Intensive Chemotherapy Alone For Induction/Consolidation In Patients 61-75 Years Old With Previously Untreated AML: A Randomized Phase III Trial (AML-17) Of The EORTC-LG and the GIMEMA-ALWP
Study Start Date : September 2002
Actual Primary Completion Date : January 2008
Actual Study Completion Date : February 2012


Arm Intervention/treatment
Experimental: ARM A
GO + MICE for remission induction followed by GO + mini-ICE for consolidation
Drug: cytarabine
Drug: etoposide
Drug: gemtuzumab ozogamicin
Drug: idarubicin
Drug: mitoxantrone hydrochloride
Active Comparator: ARM B
MICE for remission induction followed by mini-ICE for consolidation
Drug: cytarabine
Drug: etoposide
Drug: idarubicin
Drug: mitoxantrone hydrochloride



Primary Outcome Measures :
  1. Overall survival

Secondary Outcome Measures :
  1. Response (complete remission [CR] or complete remission with incomplete recovery of platelet count [CRp]) rate after induction
  2. Disease-free survival after CR/CRp
  3. Incidence of relapse after CR/CRp
  4. Incidence of death without relapse after CR/CRp
  5. Event-free survival
  6. Toxicity (highest grade) assessed by International Working Group CTC v2.0


Information from the National Library of Medicine

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Ages Eligible for Study:   61 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML)

    • Bone marrow blasts at least 20% by bone marrow aspiration or biopsy
    • FAB subtypes M0-M2 and M4-M7

      • No acute promyelocytic leukemia (FAB subtype M3)
  • Previously untreated primary or secondary AML, including AML after myelodysplastic syndromes

    • Hydroxyurea and/or corticosteroid therapy for no more than 14 days allowed
  • No blast crisis of chronic myelogenous leukemia
  • No AML supervening after other myeloproliferative diseases
  • No active CNS leukemia

PATIENT CHARACTERISTICS:

Age

  • 61 to 75

Performance status

  • WHO 0-2

Life expectancy

  • Not specified

Hematopoietic

  • WBC less than 30,000/mm^3 (pretreatment with hydroxyurea for no more than 14 days allowed)

Hepatic

  • Bilirubin no greater than 3 times upper limit of normal (ULN)

Renal

  • Creatinine no greater than 3 times ULN

Cardiovascular

  • No concurrent severe cardiovascular disease
  • No arrhythmias requiring chronic treatment
  • No congestive heart failure
  • No symptomatic ischemic heart disease

Pulmonary

  • No severe pulmonary dysfunction (CTC grade 3-4)

Other

  • HIV negative
  • No other uncontrolled infection
  • No other concurrent malignant disease
  • No severe concurrent neurological or psychiatric disease
  • No prior alcohol abuse
  • No psychological, familial, sociological, or geographical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent hematopoietic growth factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) except for life-threatening infection due to neutropenia

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • See Disease Characteristics

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No prior enrollment in this trial

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 ClinicalTrials.gov identifier (NCT number): NCT00052299


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Locations
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Austria
A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung
Linz, Austria, 4010
Allgemeines Krankenhaus - Universitatskliniken
Vienna, Austria, A-1090
Belgium
AZ Sint-Jan
Brugge, Belgium, 8000
Institut Jules Bordet
Brussels, Belgium, 1000
Hopital Universitaire Erasme
Brussels, Belgium, 1070
Centre Hospitalier Universitaire Brugmann
Brussels, Belgium, B 1020
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Hopital de Jolimont
Haine Saint Paul, Belgium, 7100
CHU Liege - Domaine Universitaire du Sart Tilman
Liege, Belgium, B-4000
Centre Hospitalier Peltzer-La Tourelle
Verviers, Belgium, B-4800
France
Hopital Edouard Herriot
Lyon, France, 69437
Centre Antoine Lacassagne
Nice, France, 06189
Hotel Dieu de Paris
Paris, France, 75181
Germany
Klinikum der Albert - Ludwigs - Universitaet Freiburg
Freiburg, Germany, D-79106
Ruprecht - Karls - Universitaet Heidelberg
Heidelberg, Germany, D-69117
Southwest German Cancer Center at Eberhard-Karls-University
Tuebingen, Germany, D-72076
Italy
Universita Degli Studi di Bari
Bari, Italy, 70124
Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
Bologna, Italy, 40138
Azienda Sanitaria di Bolzano
Bolzano, Italy, 39100
Ospedale Binaghi
Cagliari, Italy, 090100
Ospedale Oncologico A. Businco
Cagliari, Italy, 09121
Ospedale Ferrarotto
Catania, Italy, 95124
Ospedale Regionale A. Pugliese
Catanzaro, Italy, 88100
Azienda Istituti Ospitalieri
Cremona, Italy, 26100
Universita di Ferrara
Ferrara, Italy, 44100
Ospedale S. Antonio Abate
Gallarate Varese, Italy, 21013
Ospedale San Martino
Genoa, Italy, 16132
Universita degli Studi di Messina
Messina, Italy, 98122
Azienda Ospedaliera Papardo
Messina, Italy
Ospedale Civile Umberto I
Mestre, Italy, 30174
Azienda Ospedaliera - Universitaria di Modena
Modena, Italy, 41100
Azienda Ospedaliera "A. Cardarelli"
Naples, Italy, 80127
Federico II University Medical School
Naples, Italy, 80131
Azienda Ospedaliera Maggiore Della Carita
Novara, Italy, 28100
Azienda Ospedale S. Luigi at University of Torino
Orbassano, Italy, 10043
Azienda Ospedaliera Policlinico Paolo Giaccone
Palermo, Italy, 90127
Ospedale Cervello
Palermo, Italy, 90146
Ospedale La Maddalena - Palermo
Palermo, Italy
Perugia Regional Cancer Center
Perugia, Italy, 06122
Azienda Ospedale - d "S. Salvatore"
Pesaro, Italy, I-61100
Ospedale Civile Pescara
Pescara, Italy, 65100
Ospedale Sant' Eugenio
Rome, Italy, 00144
Libero Istituto Universitario Campus Bio-Medico
Rome, Italy, 00155
Universita Degli Studi "La Sapeinza"
Rome, Italy, 00161
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, Italy, 00168
H. San Giovanni-Addolorata Hospital
Rome, Italy, 00184
Istituto di Ematologia Universita - University di Sassari
Sassari, Italy, 07100
Policlinico G. B. Rossi - Borgo Roma
Verona, Italy, 37134
Ospedale San Bortolo
Vicenza, Italy, 36100
Netherlands
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, Netherlands, 5211 NL
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 HA
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands, 6500 HB
Maxima Medisch Centrum - Veldhoven
Veldhoven, Netherlands, 5500 MB
Portugal
Hospital Escolar San Joao
Porto, Portugal, 4200
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
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Study Chair: Sergio Amadori, MD Azienda Ospedallera Universitaria - Policlinico Tor Vergata, Roma

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00052299     History of Changes
Other Study ID Numbers: EORTC-06012
EORTC-06012
AML-17
GIMEMA-AML-17
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: August 27, 2012
Last Verified: August 2012
Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adult acute monocytic leukemia (M5b)
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
Additional relevant MeSH terms:
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Gemtuzumab
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Etoposide
Mitoxantrone
Idarubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antibiotics, Antineoplastic
Antineoplastic Agents, Immunological