Clinical trial NCT00052299: Chemotherapy With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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)
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: Gruppo Italiano Malattie EMatologiche dell'Adulto
First posted: 2003-01-27
Enrollment: 472
Sex: ALL
Minimum age (years): 61
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall survival
Secondary outcomes:
measure: Response (complete remission [CR] or complete remission with incomplete recovery of platelet count [CRp]) rate after induction
measure: Disease-free survival after CR/CRp
measure: Incidence of relapse after CR/CRp
measure: Incidence of death without relapse after CR/CRp
measure: Event-free survival
measure: Toxicity (highest grade) assessed by International Working Group CTC v2.0
Other outcomes:
Locations:
city: Linz
country: Austria
facility: A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus - Universitatskliniken
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Hopital Universitaire Erasme
city: Brussels
country: Belgium
facility: Centre Hospitalier Universitaire Brugmann
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Liege
country: Belgium
facility: CHU Liege - Domaine Universitaire du Sart Tilman
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hotel Dieu de Paris
city: Freiburg
country: Germany
facility: Klinikum der Albert - Ludwigs - Universitaet Freiburg
city: Heidelberg
country: Germany
facility: Ruprecht - Karls - Universitaet Heidelberg
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Bari
country: Italy
facility: Universita Degli Studi di Bari
city: Bologna
country: Italy
facility: Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi
city: Bolzano
country: Italy
facility: Azienda Sanitaria di Bolzano
city: Cagliari
country: Italy
facility: Ospedale Binaghi
city: Cagliari
country: Italy
facility: Ospedale Oncologico A. Businco
city: Catania
country: Italy
facility: Ospedale Ferrarotto
city: Catanzaro
country: Italy
facility: Ospedale Regionale A. Pugliese
city: Cremona
country: Italy
facility: Azienda Istituti Ospitalieri
city: Ferrara
country: Italy
facility: Universita di Ferrara
city: Gallarate Varese
country: Italy
facility: Ospedale S. Antonio Abate
city: Genoa
country: Italy
facility: Ospedale San Martino
city: Messina
country: Italy
facility: Universita degli Studi di Messina
city: Messina
country: Italy
facility: Azienda Ospedaliera Papardo
city: Mestre
country: Italy
facility: Ospedale Civile Umberto I
city: Modena
country: Italy
facility: Azienda Ospedaliera - Universitaria di Modena
city: Naples
country: Italy
facility: Azienda Ospedaliera "A. Cardarelli"
city: Naples
country: Italy
facility: Federico II University Medical School
city: Novara
country: Italy
facility: Azienda Ospedaliera Maggiore Della Carita
city: Orbassano
country: Italy
facility: Azienda Ospedale S. Luigi at University of Torino
city: Palermo
country: Italy
facility: Azienda Ospedaliera Policlinico Paolo Giaccone
city: Palermo
country: Italy
facility: Ospedale Cervello
city: Palermo
country: Italy
facility: Ospedale La Maddalena - Palermo
city: Perugia
country: Italy
facility: Perugia Regional Cancer Center
city: Pesaro
country: Italy
facility: Azienda Ospedale - d "S. Salvatore"
city: Pescara
country: Italy
facility: Ospedale Civile Pescara
city: Rome
country: Italy
facility: Ospedale Sant' Eugenio
city: Rome
country: Italy
facility: Libero Istituto Universitario Campus Bio-Medico
city: Rome
country: Italy
facility: Universita Degli Studi "La Sapeinza"
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Rome
country: Italy
facility: H. San Giovanni-Addolorata Hospital
city: Sassari
country: Italy
facility: Istituto di Ematologia Universita - University di Sassari
city: Verona
country: Italy
facility: Policlinico G. B. Rossi - Borgo Roma
city: Vicenza
country: Italy
facility: Ospedale San Bortolo
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum - Veldhoven
city: Porto
country: Portugal
facility: Hospital Escolar San Joao
Study officials:
affiliation: Azienda Ospedallera Universitaria - Policlinico Tor Vergata, Roma
name: Sergio Amadori, MD
role: STUDY_CHAIR
References:
citation: 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.