Liposomal Cytarabine and Daunorubicin (CPX-351) for Adults With Untreated High-Risk MDS and Non-APL AML at High Risk of Treatment-Related Mortality
Laboratory Biomarker Analysis
+ Liposomal Cytarabine-Daunorubicin CPX-351
+ Laboratory Biomarker Analysis
Maladies de la moelle osseuse+12
+ Maladies Hématologiques
+ Maladies hématologiques et lymphatiques
Étude thérapeutique
Résumé
Date de début de l'étude : 7 mai 2013
Date à laquelle le premier participant a commencé l'étude.PRIMARY OBJECTIVES: I. Estimate whether the 32 units/m^2 or the 64 units/m^2 or both dose levels of CPX-351 (liposomal cytarabine-daunorubicin CPX-351) are likely to improve treatment-related mortality (TRM) rate while keeping the complete remission (CR) rate constant in patients with untreated high-risk myelodysplastic syndrome (MDS) or non-acute promyelocytic leukemia (APL) acute myeloid leukemia (AML) at high risk of TRM. SECONDARY OBJECTIVES: I. Describe the CR/CR with incomplete platelet count recovery (CRp) rate after up to 4 cycles of induction/re-induction therapy. II. Describe the event-free survival, disease-free survival, and overall survival of patients who achieve CR/CRp. III. Estimate the frequency and severity of regimen-associated toxicities. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: INDUCTION/RE-INDUCTION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation. CONSOLIDATION: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. ARM II: (closed to accrual effective 4/21/14) INDUCTION/RE-INDUCTION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or CRp continue on to consolidation. CONSOLIDATION: Patients receive higher-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1 and 3. Treatment repeats every 40 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 1 month.
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.48 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 18 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
Inclusion Criteria: Diagnosis of untreated "high-risk" MDS (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available Prior hydroxyurea for AML is permitted but should be discontinued prior to start of CPX-351 treatment Azacitidine, decitabine, lenalidomide, and growth factors are permitted for low-risk MDS (< 10% blasts); all treatments for MDS should be discontinued prior to start of CPX-351 treatment Treatment-related mortality (TRM) score >= 13.1 as calculated with simplified model Bilirubin < 2.0 mg/mL x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 4.0 x upper limit of normal; this requirement reflects the excretion of CPX-351 by the liver Left ventricular ejection fraction (LVEF) >= 40%, assessed within 28 days prior to registration, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) > 100,000/uL can be treated with leukapheresis prior to enrollment Provide signed written informed consent Exclusion Criteria: Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML) Concomitant illness associated with a likely survival of < 1 year Active systemic fungal, bacterial, viral, or other infection, unless under treatment with anti-microbials and controlled/stable, as defined as being afebrile and hemodynamically stable for 24-48 hours
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.2 groupes d'intervention sont désignés dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalGroupe II
ExpérimentalObjectifs 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 2 sites
Fred Hutch/University of Washington Cancer Consortium
Seattle, United States