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

NCT ID: NCT00052299

Last Updated: 2012-08-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 472 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-09-30
• Study Completion Date: 2012-02-29

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.

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.

Conditions

Leukemia

Keywords

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARM A

GO + MICE for remission induction followed by GO + mini-ICE for consolidation

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

gemtuzumab ozogamicin

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

ARM B

MICE for remission induction followed by mini-ICE for consolidation

Group Type: ACTIVE_COMPARATOR

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

Interventions

cytarabine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

gemtuzumab ozogamicin

Intervention Type: DRUG

idarubicin

Intervention Type: DRUG

mitoxantrone hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 61 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Amadori, MD

Role: STUDY_CHAIR

Azienda Ospedallera Universitaria - Policlinico Tor Vergata, Roma

Locations

A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung

Linz, , Austria

Allgemeines Krankenhaus - Universitatskliniken

Vienna, , Austria

AZ Sint-Jan

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Centre Hospitalier Universitaire Brugmann

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

CHU Liege - Domaine Universitaire du Sart Tilman

Liège, , Belgium

Centre Hospitalier Peltzer-La Tourelle

Verviers, , Belgium

Hopital Edouard Herriot

Lyon, , France

Centre Antoine Lacassagne

Nice, , France

Hotel Dieu de Paris

Paris, , France

Klinikum der Albert - Ludwigs - Universitaet Freiburg

Freiburg im Breisgau, , Germany

Ruprecht - Karls - Universitaet Heidelberg

Heidelberg, , Germany

Southwest German Cancer Center at Eberhard-Karls-University

Tübingen, , Germany

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

Universita degli Studi di Messina

Messina, , Italy

Azienda Ospedaliera Papardo

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

Ospedale Sant' Eugenio

Rome, , Italy

Libero Istituto Universitario Campus Bio-Medico

Rome, , Italy

Universita Degli Studi "La Sapeinza"

Rome, , Italy

Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore

Rome, , Italy

H. San Giovanni-Addolorata Hospital

Rome, , Italy

Istituto di Ematologia Universita - University di Sassari

Sassari, , Italy

Policlinico G. B. Rossi - Borgo Roma

Verona, , Italy

Ospedale San Bortolo

Vicenza, , Italy

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, , Netherlands

Hospital Escolar San Joao

Porto, , Portugal

Countries

Austria; Belgium; France; Germany; Italy; Netherlands; Portugal

References

Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, De Fabritiis P, Venditti A, Ho AD, Lubbert M, Thomas X, Latagliata R, Halkes CJ, Falzetti F, Magro D, Guimaraes JE, Berneman Z, Specchia G, Karrasch M, Fazi P, Vignetti M, Willemze R, de Witte T, Marie JP. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013 Dec 10;31(35):4424-30. doi: 10.1200/JCO.2013.49.0771. Epub 2013 Oct 14.

Reference Type: DERIVED

PMID: 24127442 (View on PubMed)

Other Identifiers

EORTC-06012

Identifier Type: -

Identifier Source: secondary_id

AML-17

Identifier Type: -

Identifier Source: secondary_id

GIMEMA-AML-17

Identifier Type: -

Identifier Source: secondary_id

EORTC-06012

Identifier Type: -

Identifier Source: org_study_id