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
Collecte de données
Anomalies Congénitales+14
+ Maladies de la moelle osseuse
+ Leucémie érythroblastique aiguë
Étude thérapeutique
Résumé
Date de début de l'étude : 1 juin 2004
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.279 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 61 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Objectifs de l'étude
Objectifs principaux
Objectifs secondaires
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 45 sites
Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli
Naples, ItalyOspedale Maggiore della Carita
Novara, ItalyAzienda Ospedaliera Policlinico Paolo Giaccone
Palermo, Italy