AML-19Gemtuzumab Ozogamicin (GO) Monotherapy Versus Standard Supportive Care for Previously Untreated AML in Elderly Patients Who Are Not Eligible for Intensive Chemotherapy: A Randomized Phase II/III Trial (AML-19) of the EORTC-LG and GIMEMA-ALWP
Data Collection
Congenital Abnormalities+14
+ Bone Marrow Diseases
+ Leukemia, Erythroblastic, Acute
Treatment Study
Summary
Study start date: June 1, 2004
Actual date on which the first participant was enrolled.OBJECTIVES: * Compare the feasibility, toxicity, and antileukemic activity of two different dosing regimens of gemtuzumab ozogamicin (GO) vs standard supportive care in older patients with previously untreated acute myeloid leukemia who are not candidates for intensive chemotherapy. (phase II) * Compare the efficacy and toxicity of the best dosing regimen of GO selected from phase II vs standard supportive care, in terms of overall survival, in these patients. (phase III) OUTLINE: This is a randomized, open-label, multicenter phase II study followed by a phase III study. Patients are stratified according to age (61 to 75 vs 76 to 80 vs 81 and over), CD33-positivity of bone marrow blasts (< 20% vs 20-80% vs > 80% vs unknown), initial WBC before hydroxyurea administration (< 30,000/mm\^3 vs ≥ 30,000/mm\^3), WHO performance status (0-1 vs 2 vs 3-4), and participating center. * Phase II: Patients are randomized to 1 of 3 treatment arms. * Arm I: Patients receive gemtuzumab ozogamicin (GO) IV over 2 hours on days 1 and 8. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. * Arm II: Patients receive GO IV over 2 hours on days 1, 3, and 5. Patients with stable or responding disease at day 36 receive GO IV over 2 hours every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. * Arm III: Patients receive standard supportive care. * Phase III: Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive the selected treatment (arm I or arm II) from phase II. * Arm II: Patients receive standard supportive care. Patients who receive GO treatment are followed monthly for 1 year and then every 3 months thereafter. Patients who receive standard supportive care are followed at least every 4 weeks. PROJECTED ACCRUAL: A total of 259 patients (75 for phase II \[25 per treatment arm\] and 184 for phase III \[92 per treatment arm\]) will be accrued for this study within 2.5 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.279 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 61 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: * Histologically confirmed acute myeloid leukemia (AML) * At least 20% bone marrow blasts by bone marrow aspiration or biopsy * All subtypes except M3 (acute promyelocytic leukemia) are allowed * Previously untreated primary or secondary disease (including AML after myelodysplastic syndromes) * Ineligible for intensive chemotherapy, as defined by 1 of the following criteria: * 61 to 75 years old AND WHO performance status \> 2 AND/OR unwilling to receive intensive chemotherapy * Over 75 years old * No blast crisis of chronic myeloid leukemia * No AML supervention after other myeloproliferative disease * WBC \< 30,000/mm\^3 and meets 1 of the following criteria: * WBC \< 30,000/mm\^3 at diagnosis AND had no prior treatment with hydroxyurea * WBC ≥ 30,000/mm\^3 at diagnosis AND received mandatory pretreatment with hydroxyurea (up to 14 days duration) until WBC \< 30,000/mm\^3 * No active CNS leukemia PATIENT CHARACTERISTICS: Age * See Disease Characteristics * 61 and over Performance status * See Disease Characteristics Life expectancy * Not specified Hematopoietic * See Disease Characteristics Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) Renal * Creatinine ≤ 1.5 times ULN Cardiovascular * No arrhythmia requiring chronic treatment * No congestive heart failure * No symptomatic ischemic heart disease * No other severe cardiovascular disease Pulmonary * No severe pulmonary dysfunction ≥ grade 3 Other * No alcohol abuse * No severe neurological or psychiatric disease * No active uncontrolled infection or severe systemic infection * No other malignancy * No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up * HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) * No concurrent antiangiogenic drugs Chemotherapy * See Disease Characteristics * Concurrent low-dose cytostatic agents (i.e., thioguanine or mercaptopurine) allowed for palliative care (standard supportive care arm only) Endocrine therapy * Prior corticosteroids (duration ≤ 14 days ) for primary or secondary AML allowed Radiotherapy * Not specified Surgery * Not specified Other * No other concurrent cytotoxic drugs * No other concurrent experimental therapy * No concurrent tyrosine kinase inhibitors
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.Study Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 45 locations
Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli
Naples, ItalyOspedale Maggiore della Carita
Novara, ItalyAzienda Ospedaliera Policlinico Paolo Giaccone
Palermo, Italy