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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00052299

Collaborator

Gruppo Italiano Malattie EMatologiche dell'Adulto (Other)

472

Enrollment

Locations

Arms

113

Duration (Months)

8.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

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 :

Sep 1, 2002

Actual Primary Completion Date :

Jan 1, 2008

Actual Study Completion Date :

Feb 1, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall survival []

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

61 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung	Linz	Austria	4010
2	Allgemeines Krankenhaus - Universitatskliniken	Vienna	Austria	A-1090
3	AZ Sint-Jan	Brugge	Belgium	8000
4	Institut Jules Bordet	Brussels	Belgium	1000
5	Hopital Universitaire Erasme	Brussels	Belgium	1070
6	Centre Hospitalier Universitaire Brugmann	Brussels	Belgium	B 1020
7	Universitair Ziekenhuis Antwerpen	Edegem	Belgium	B-2650
8	Hopital de Jolimont	Haine Saint Paul	Belgium	7100
9	CHU Liege - Domaine Universitaire du Sart Tilman	Liege	Belgium	B-4000
10	Centre Hospitalier Peltzer-La Tourelle	Verviers	Belgium	B-4800
11	Hopital Edouard Herriot	Lyon	France	69437
12	Centre Antoine Lacassagne	Nice	France	06189
13	Hotel Dieu de Paris	Paris	France	75181
14	Klinikum der Albert - Ludwigs - Universitaet Freiburg	Freiburg	Germany	D-79106
15	Ruprecht - Karls - Universitaet Heidelberg	Heidelberg	Germany	D-69117
16	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen	Germany	D-72076
17	Universita Degli Studi di Bari	Bari	Italy	70124
18	Azienda Ospedaliera Di Bologna Policlinico S. Orsola - Malpighi	Bologna	Italy	40138
19	Azienda Sanitaria di Bolzano	Bolzano	Italy	39100
20	Ospedale Binaghi	Cagliari	Italy	090100
21	Ospedale Oncologico A. Businco	Cagliari	Italy	09121
22	Ospedale Ferrarotto	Catania	Italy	95124
23	Ospedale Regionale A. Pugliese	Catanzaro	Italy	88100
24	Azienda Istituti Ospitalieri	Cremona	Italy	26100
25	Universita di Ferrara	Ferrara	Italy	44100
26	Ospedale S. Antonio Abate	Gallarate Varese	Italy	21013
27	Ospedale San Martino	Genoa	Italy	16132
28	Universita degli Studi di Messina	Messina	Italy	98122
29	Azienda Ospedaliera Papardo	Messina	Italy
30	Ospedale Civile Umberto I	Mestre	Italy	30174
31	Azienda Ospedaliera - Universitaria di Modena	Modena	Italy	41100
32	Azienda Ospedaliera "A. Cardarelli"	Naples	Italy	80127
33	Federico II University Medical School	Naples	Italy	80131
34	Azienda Ospedaliera Maggiore Della Carita	Novara	Italy	28100
35	Azienda Ospedale S. Luigi at University of Torino	Orbassano	Italy	10043
36	Azienda Ospedaliera Policlinico Paolo Giaccone	Palermo	Italy	90127
37	Ospedale Cervello	Palermo	Italy	90146
38	Ospedale La Maddalena - Palermo	Palermo	Italy
39	Perugia Regional Cancer Center	Perugia	Italy	06122
40	Azienda Ospedale - d "S. Salvatore"	Pesaro	Italy	I-61100
41	Ospedale Civile Pescara	Pescara	Italy	65100
42	Ospedale Sant' Eugenio	Rome	Italy	00144
43	Libero Istituto Universitario Campus Bio-Medico	Rome	Italy	00155
44	Universita Degli Studi "La Sapeinza"	Rome	Italy	00161
45	Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore	Rome	Italy	00168
46	H. San Giovanni-Addolorata Hospital	Rome	Italy	00184
47	Istituto di Ematologia Universita - University di Sassari	Sassari	Italy	07100
48	Policlinico G. B. Rossi - Borgo Roma	Verona	Italy	37134
49	Ospedale San Bortolo	Vicenza	Italy	36100
50	Jeroen Bosch Ziekenhuis	's-Hertogenbosch	Netherlands	5211 NL
51	Onze Lieve Vrouwe Gasthuis	Amsterdam	Netherlands	1091 HA
52	Leiden University Medical Center	Leiden	Netherlands	2300 CA
53	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen	Netherlands	6500 HB
54	Maxima Medisch Centrum - Veldhoven	Veldhoven	Netherlands	5500 MB
55	Hospital Escolar San Joao	Porto	Portugal	4200