Publication Date:
2017-12-07
Description:
Background: CPX-351 is a liposomal formulation of 5:1 molar combination of cytarabine and daunorubicin (Leukemia research 2010; 34: 1214). Subset analysis in a Phase II study reported improved outcomes in first relapse AML pts with European Prognostic Index defined poor-risk disease (Cancer 2015; 121: 234). In a phase 3 randomized study among fit pts, 60-75 years (yrs) of age with high-risk AML, that compared induction CPX-351 (100 U/m2, days 1, 3, 5) and vs 7+3; CPX-351 significantly improved response, event free and overall survival (Journal of Clinical Oncology 2016; 34(15_suppl): 7000). Observations from the Phase I study of responses occurring at dose levels of one third to one half the MTD (32 to 43 U/m2), suggest that doses of 75 and 50 units/m2 may still be effective and better tolerated among pts at high risk for toxicity. Hypothesis: Reduced dose CPX-351 as induction therapy may improve the outcome of pts with AML at high risk for 60-day mortality and not ordinarily offered induction therapy. Design: We designed an open-label, phase II trial of CPX-351 administered on days 1, 3, and 5 at 50 (arm 1) or 75 (arm 2) units/m2 as induction. Fifteen pts each were to be randomly assigned to these two arms. As these doses are below the original MTD dose of 100 units/m2, a cohort of 15 pts were to be studied at 100 units/m2 provided the first two dose levels were safe. At the end of the study a single dose level was to be chosen based on efficacy and safety i.e. dose limiting toxicity (DLT)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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