Clinical trial NCT00006122: Gemtuzumab Ozogamicin With or Without Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia
Official title: Gemtuzumab Ozogamicin (CMA-676) Followed or Not by Intensive Chemotherapy as Initial Treatment for Elderly Patients With Acute Myeloid Leukemia: An EORTC-LG Pilot Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: untreated adult acute myeloid leukemia
adult acute erythroid leukemia (M6)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute megakaryoblastic leukemia (M7)
secondary acute myeloid leukemia
adult acute monocytic leukemia (M5b)
adult acute minimally differentiated myeloid leukemia (M0)
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2004-02-16
Enrollment: 106
Sex: ALL
Minimum age (years): 61
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy uses different ways to stop cancer cells from dividing so they stop growing or die. Combining gemtuzumab ozogamicin with chemotherapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of gemtuzumab ozogamicin with or without chemotherapy in treating older patients who have acute myeloid leukemia.

Detailed description: OBJECTIVES: I. Determine the feasibility, toxicity, and antileukemic activity of gemtuzumab ozogamicin (CMA-676) with or without mitoxantrone, etoposide, cytarabine, and idarubicin in elderly patients with acute myeloid leukemia.

OUTLINE: This is a multicenter study. Patients are stratified according to risk (standard risk, defined as age 61-75 and WHO performance status 0-1 vs poor risk, defined as over 75 years and WHO performance status 0-2 OR under 76 years and WHO performance status 2). Frontline therapy: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15. Stratum I (Standard risk patients): Patients with disease progression at any time during frontline therapy may begin induction therapy immediately. Induction therapy begins 7-10 days after response assessment regardless of response and in the absence of unacceptable toxicity. Stratum II (Poor risk patients): Patients experiencing complete remission with or without platelet recovery will begin consolidation therapy within 4-8 weeks of response assessment in the absence of unacceptable toxicity. Stratum I Induction therapy: 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. Patients experiencing partial response are given a second induction therapy course. Patients experiencing complete remission with or without platelet recovery after 1 or 2 induction courses begin consolidation therapy within 4-8 weeks of response assessment in the absence of unacceptable toxicity. Consolidation therapy: Patients receive 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. Stratum II Consolidation therapy: Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and then 1-3 months later. Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 45-82 (28-49 for stratum I, and 17-33 for stratum II) patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Diagnosis of primary or secondary acute myeloid leukemia (AML) Previously untreated At least 20% marrow blasts AML after myelodysplastic syndrome allowed No leukemia after other myeloproliferative diseases No acute promyelocytic leukemia (M3) or blastic phase chronic myelogenous leukemia No active CNS leukemia

PATIENT CHARACTERISTICS: Age: 61 and over Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics White blood count no greater than 30,000/mm3 unless reducible to less than 30,000/mm3 by a maximum of 7 days of hydroxyurea Hepatic: Bilirubin no greater than 3 times upper limit of normal (ULN) Renal: Creatinine no greater than 3 times ULN Cardiovascular: No severe heart failure that would preclude study Pulmonary: No severe lung failure that would preclude study Other: No other concurrent malignancies No active uncontrolled infection No concurrent severe neurological or psychiatric disease No psychological, familial, sociological or geographical condition that would preclude compliance with study HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior humanized monoclonal antibody therapy Chemotherapy: Up to 7 days of prior hydroxyurea allowed At least 24 hours since prior hydroxyurea No other prior chemotherapy for AML Endocrine therapy: No more than 7 days of prior corticosteroids No other prior endocrine therapy Radiotherapy: No prior radiotherapy Surgery: Not specified

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Innsbruck Universitaetsklinik
city: Brugge
country: Belgium
facility: A.Z. St. Jan
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Liege
country: Belgium
facility: CHU Sart-Tilman
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Paris
country: France
facility: Hotel Dieu de Paris
city: Paris
country: France
facility: Hopital Necker
city: Heidelberg
country: Germany
facility: Medizinische Klinik und Poliklinik
city: Tuebingen
country: Germany
facility: Eberhard Karls Universitaet
city: Bolzano
country: Italy
facility: Ospedale Generale Regionale
city: Reggio Calabria
country: Italy
facility: Ospedali Riuniti
city: Rome
country: Italy
facility: Ospedale San Eugenio
city: Rome
country: Italy
facility: Azienda Policlinico Umberto Primo
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: 's-Hertogenbosch
country: Netherlands
facility: Groot Ziekengasthuis 's-Hertogenbosch
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
Study officials:
affiliation: Ospedale Sant' Eugenio
name: Sergio Amadori, MD
role: STUDY_CHAIR
References:
citation: Seedhouse CH, Grundy M, White P, Li Y, Fisher J, Yakunina D, Moorman AV, Hoy T, Russell N, Burnett A, Pallis M; National Cancer Research Network. Sequential influences of leukemia-specific and genetic factors on p-glycoprotein expression in blasts from 817 patients entered into the National Cancer Research Network acute myeloid leukemia 14 and 15 trials. Clin Cancer Res. 2007 Dec 1;13(23):7059-66. doi: 10.1158/1078-0432.CCR-07-1484.
citation: Amadori S, Suciu S, Willemze R, et al.: Up-front window trial of gemtuzumab ozogamicin (GO) in previously untreated elderly patients with AML: an EORTC leukemia group study. [Abstract] Blood 104 (11): A-877, 2004.
citation: Amadori S, Suciu S, Willemze R, Mandelli F, Selleslag D, Stauder R, Ho A, Denzlinger C, Leone G, Fabris P, Muus P, Vignetti M, Hagemeijer A, Beeldens F, Anak O, De Witte T; EORTC leukemia group; GIMEMA leukemia group. Sequential administration of gemtuzumab ozogamicin and conventional chemotherapy as first line therapy in elderly patients with acute myeloid leukemia: a phase II study (AML-15) of the EORTC and GIMEMA leukemia groups. Haematologica. 2004 Aug;89(8):950-6.