Chemotherapy With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia

Leukemia Clinical Trial

— AML-17  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00052299
• Other study ID #: EORTC-06012
• Secondary ID: EORTC-06012AML-1
• Status: Completed
• Phase: Phase 3
• First received: January 24, 2003
• Last updated: August 24, 2012
• Start date: September 2002
• Est. completion date: February 2012

Study information

• Verified date: August 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 472
• Est. completion date: February 2012
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 61 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• cytarabine

• etoposide

• gemtuzumab ozogamicin

• idarubicin

• mitoxantrone hydrochloride

Locations

Country	Name	City	State
Austria	A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung	Linz
Austria	Allgemeines Krankenhaus - Universitatskliniken	Vienna
Belgium	AZ Sint-Jan	Brugge
Belgium	Centre Hospitalier Universitaire Brugmann	Brussels
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Hopital de Jolimont	Haine Saint Paul
Belgium	CHU Liege - Domaine Universitaire du Sart Tilman	Liege
Belgium	Centre Hospitalier Peltzer-La Tourelle	Verviers
France	Hopital Edouard Herriot	Lyon
France	Centre Antoine Lacassagne	Nice
France	Hotel Dieu de Paris	Paris
Germany	Klinikum der Albert - Ludwigs - Universitaet Freiburg	Freiburg
Germany	Ruprecht - Karls - Universitaet Heidelberg	Heidelberg
Germany	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen
Italy	Universita Degli Studi di Bari	Bari
Italy	Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi	Bologna
Italy	Azienda Sanitaria di Bolzano	Bolzano
Italy	Ospedale Binaghi	Cagliari
Italy	Ospedale Oncologico A. Businco	Cagliari
Italy	Ospedale Ferrarotto	Catania
Italy	Ospedale Regionale A. Pugliese	Catanzaro
Italy	Azienda Istituti Ospitalieri	Cremona
Italy	Universita di Ferrara	Ferrara
Italy	Ospedale S. Antonio Abate	Gallarate Varese
Italy	Ospedale San Martino	Genoa
Italy	Azienda Ospedaliera Papardo	Messina
Italy	Universita degli Studi di Messina	Messina
Italy	Ospedale Civile Umberto I	Mestre
Italy	Azienda Ospedaliera - Universitaria di Modena	Modena
Italy	Azienda Ospedaliera "A. Cardarelli"	Naples
Italy	Federico II University Medical School	Naples
Italy	Azienda Ospedaliera Maggiore Della Carita	Novara
Italy	Azienda Ospedale S. Luigi at University of Torino	Orbassano
Italy	Azienda Ospedaliera Policlinico Paolo Giaccone	Palermo
Italy	Ospedale Cervello	Palermo
Italy	Ospedale La Maddalena - Palermo	Palermo
Italy	Perugia Regional Cancer Center	Perugia
Italy	Azienda Ospedale - d "S. Salvatore"	Pesaro
Italy	Ospedale Civile Pescara	Pescara
Italy	H. San Giovanni-Addolorata Hospital	Rome
Italy	Libero Istituto Universitario Campus Bio-Medico	Rome
Italy	Ospedale Sant' Eugenio	Rome
Italy	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome
Italy	Universita Degli Studi "La Sapeinza"	Rome
Italy	Istituto di Ematologia Universita - University di Sassari	Sassari
Italy	Policlinico G. B. Rossi - Borgo Roma	Verona
Italy	Ospedale San Bortolo	Vicenza
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	Maxima Medisch Centrum - Veldhoven	Veldhoven
Portugal	Hospital Escolar San Joao	Porto

Sponsors (2)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Gruppo Italiano Malattie EMatologiche dell'Adulto

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Italy,  Netherlands,  Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival			No
Secondary	Response (complete remission [CR] or complete remission with incomplete recovery of platelet count [CRp]) rate after induction			No
Secondary	Disease-free survival after CR/CRp			No
Secondary	Incidence of relapse after CR/CRp			No
Secondary	Incidence of death without relapse after CR/CRp			No
Secondary	Event-free survival			No
Secondary	Toxicity (highest grade) assessed by International Working Group CTC v2.0			Yes