Cytarabine and Daunorubicin With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
Randomised Induction and Post Induction Therapy in Older Patients (≥61 Years of Age) With Acute Myeloid Leukemia (AML) and Refractory Anemia With Excess Blasts (RAEB, RAEB-t)
RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether cytarabine and daunorubicin followed by gemtuzumab ozogamicin is more effective than cytarabine and daunorubicin in treating acute myeloid leukemia or myelodysplastic syndromes.
PURPOSE: This randomized phase III trial is studying cytarabine and two different doses of daunorubicin to see how well they work compared to cytarabine and daunorubicin followed by gemtuzumab ozogamicin in treating older patients with acute myeloid leukemia or myelodysplastic syndromes.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
OBJECTIVES:
Primary
- Compare the event-free and disease-free survival of older patients with acute myeloid leukemia, refractory anemia with excess blasts (RAEB), or RAEB in transformation treated with induction therapy comprising cytarabine in combination with two different doses of daunorubicin followed by cytarabine alone with or without post-induction therapy comprising gemtuzumab ozogamicin.
Secondary
- Compare the complete remission rate in patients treated with these regimens.
- Compare the overall survival of patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Determine the probability of relapse and death during first complete remission in patients treated with post-induction gemtuzumab ozogamicin.
- Correlate prognostic factors (e.g., CD33 positivity, multidrug resistance phenotype, or cytogenetics) with probability of complete remission and overall, event-free, and disease-free survival of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and diagnosis (acute myeloid leukemia [AML] vs myelodysplastic syndromes [MDS]) for induction therapy. Patients are stratified according to participating center, diagnosis (AML vs MDS), induction treatment arm (I vs II), and response to induction therapy (complete remission [CR] vs no CR) for post-induction therapy.
Induction therapy (course 1): Patients are randomized to 1 of 2 induction treatment arms.
- Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 3 hours on days 1-3.
- Arm II: Patients receive cytarabine as in arm I and daunorubicin as in arm I but at a higher dose.
Approximately 28-35 days after the start of course 1 (or sooner if the bone marrow shows evidence of resistant disease), patients in both arms proceed to course 2 of induction therapy.
- Induction therapy (course 2): All patients receive cytarabine IV over 6 hours twice daily on days 1-6.
After completion of course 2, patients undergo assessment of remission status. Patients who do not achieve CR are removed from the study. Patients achieving CR proceed to post-induction therapy and undergo a second randomization.
Post-induction therapy: Patients are randomized to 1 of 2 post-induction treatment arms.
- Arm I: Patients receive no further chemotherapy.
- Arm II: Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1, 29, and 57 in the absence of disease relapse or unacceptable toxicity.
After completion of study treatment, patients are followed monthly for 1 year, every 3 months for 2 years, every 4-6 months for 2 years, and then periodically thereafter.
PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 4-5 years.
Type d'étude
Inscription (Anticipé)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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England
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Basingstoke, England, Royaume-Uni, RG24 9NA
- North Hampshire Hospital
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Canterbury, England, Royaume-Uni, CT2 7NR
- Kent and Canterbury Hospital
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Gillingham Kent, England, Royaume-Uni, ME7 5NY
- Medway Maritime Hospital
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Maidstone, England, Royaume-Uni, ME16 9QQ
- Maidstone Hospital
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Truro, Cornwall, England, Royaume-Uni, TR1 3LJ
- Royal Cornwall Hospital
-
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Wales
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Cardiff, Wales, Royaume-Uni, CF14 4XW
- University Hospital of Wales
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed diagnosis of 1 of the following:
Acute myeloid leukemia (AML)
M0-M2 or M4-M7 FAB subtype
- No AML with cytogenetic abnormality t(15;17) (M3)
- Patients with secondary AML progressing from prior myelodysplasia* or biphenotypic leukemia are eligible
Refractory anemia with excess blasts (RAEB) or RAEB in transformation
- International Prognostic Scoring System score ≥ 1.5 NOTE: *Any prior hematological disease of ≥ 4 months duration
- No chronic myelogenous leukemia in blastic crisis
- No prior polycythemia rubra vera
- No primary myelofibrosis
PATIENT CHARACTERISTICS:
Age
- 61 and over
Performance status
- WHO 0-2
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- ALT and/or AST ≤ 2.5 times upper limit of normal (ULN)*
- Bilirubin ≤ 2 times ULN* NOTE: *Unless elevation is caused by organ infiltration by AML
Renal
- Creatinine ≤ 2 times ULN* NOTE: *Unless elevation is caused by organ infiltration by AML
Cardiovascular
- No myocardial infarction within the past 6 months
- LVEF > 50% by MUGA, echocardiogram, or other methods
- No unstable angina
- No unstable cardiac arrhythmia
- No severe and/or uncontrolled hypertension
Other
- No uncontrolled diabetes
- No severe and/or uncontrolled infection
- No other severe and/or uncontrolled medical condition
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 6 months since prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- No prior induction therapy for AML or myelodysplastic syndromes
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Comparateur actif: Arm A low dose Dauno
Induction 45 mg Dauno
|
|
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Expérimental: ARM B high dose Dauno
Induction 90 mg Dauno
|
|
|
Aucune intervention: Arm 1 no further treatment
|
|
|
Expérimental: Arm 2 Mylotarg
Post induction treatment with Mylotarg
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
|---|
|
Event-free survival after induction therapy
|
|
Disease-free survival after maintenance therapy
|
Mesures de résultats secondaires
Mesure des résultats |
|---|
|
Complete remission (CR) rate after induction therapy
|
|
Overall survival after induction therapy
|
|
Toxicity after induction therapy
|
|
Toxicity after maintenance therapy
|
|
Probability of relapse and death in first CR after maintenance therapy
|
|
Overall survival after maintenance therapy
|
Collaborateurs et enquêteurs
Les enquêteurs
- Chaise d'étude: Jonathan Kell, MRCPath, University Hospital of Wales
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
- anémie réfractaire avec excès de blastes
- anémie réfractaire avec excès de blastes en transformation
- syndromes myélodysplasiques de novo
- syndromes myélodysplasiques secondaires
- leucémie myéloïde aiguë de l'adulte avec anomalies 11q23 (MLL)
- leucémie myéloïde aiguë de l'adulte avec inv(16)(p13;q22)
- leucémie myéloïde aiguë de l'adulte avec t(16;16)(p13;q22)
- leucémie myéloïde aiguë de l'adulte avec t(8;21)(q22;q22)
- leucémie myéloïde aiguë secondaire
- leucémie myéloïde aiguë de l'adulte non traitée
- leucémie aiguë mégacaryoblastique de l'adulte (M7)
- leucémie myéloïde aiguë peu différenciée de l'adulte (M0)
- leucémie aiguë monoblastique de l'adulte (M5a)
- leucémie monocytaire aiguë de l'adulte (M5b)
- leucémie aiguë myéloblastique de l'adulte avec maturation (M2)
- leucémie aiguë myéloblastique de l'adulte sans maturation (M1)
- leucémie aiguë myélomonocytaire de l'adulte (M4)
- érythroleucémie adulte (M6a)
- leucémie érythroïde pure de l'adulte (M6b)
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Tumeurs par type histologique
- Tumeurs
- Maladie
- Maladies de la moelle osseuse
- Maladies hématologiques
- Anémie
- Conditions précancéreuses
- Anémie réfractaire
- Syndrome
- Syndromes myélodysplasiques
- Leucémie
- Leucémie myéloïde
- Leucémie, myéloïde, aiguë
- Préleucémie
- Anémie, réfractaire, avec excès de blastes
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Agents antinéoplasiques immunologiques
- Antibiotiques, Antinéoplasiques
- Cytarabine
- Daunorubicine
- Gemtuzumab
Autres numéros d'identification d'étude
- CDR0000433422
- SAKK-AML-43
- EU-20514
- HOVON-AML-43
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