Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/ daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML Journal Article
| Authors: | Lancet, J. E.; Cortes, J. E.; Hogge, D. E.; Tallman, M. S.; Kovacsovics, T. J.; Damon, L. E.; Komrokji, R.; Solomon, S. R.; Kolitz, J. E.; Cooper, M.; Yeager, A. M.; Louie, A. C.; Feldman, E. J. |
| Article Title: | Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/ daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML |
| Abstract: | CPX-351 is a liposomal formulation of cytarabine:daunorubicin designed to deliver synergistic drug ratios to leukemia cells. In this phase 2 study, newly diagnosed older acute myeloid leukemia (AML) patients were randomized 2:1 to first-line CPX-351 or 7+3 treatment. The goal was to determine efficacy and identify patient subgroups that may benefit from CPX-351 treatment. Response rate (complete remission + incomplete remission) was the primary end point, with event-free survival (EFS) and overall survival (OS) as secondary end points. The 126 patients entered were balanced for disease and patient-specific risk factors. Overall, CPX-351 produced higher response rates (66.7% vs 51.2%,P=.07), meeting predefined criteria for success (P< .1). Differences in EFS andOS were not statistically significant.Aplanned analysis of the secondaryAMLsubgroup demonstrated an improved response rate (57.6% vs 31.6%, P= .06), and prolongation of EFS (hazard ratio [HR]= 0.59, P =.08) and OS (HR 50.46, P =.01). Recovery from cytopenias was slower after CPX-351 (median days to absolute neutrophil count ≥1000: 36 vs 32; platelets >100 000: 37 vs 28) with more grade 3-4 infections but without increase in infection-related deaths (3.5% vs 7.3%) or 60-day mortality (4.7% vs 14.6%), indicating acceptable safety. These results suggest a clinical benefit with CPX-351, particularly among patients with secondary AML, and provide the rationale for a phase 3 trial currently underway in newly diagnosed secondary AML patients. This study is registered at Clinicaltrials. gov as #NCT00788892. © 2014 by The American Society of Hematology. |
| Keywords: | adult; cancer survival; controlled study; event free survival; treatment outcome; treatment response; aged; unclassified drug; acute granulocytic leukemia; major clinical study; overall survival; constipation; fatigue; neutropenia; salvage therapy; cancer combination chemotherapy; diarrhea; drug dose reduction; drug efficacy; drug safety; cancer patient; cytarabine; follow up; prospective study; imatinib; edema; drug eruption; neutrophil count; phase 2 clinical trial; nausea; randomized controlled trial; thrombocytopenia; kidney failure; continuous infusion; risk factor; cancer mortality; dyspnea; febrile neutropenia; pneumonia; hypoxia; acute kidney failure; drug fatality; hypokalemia; multicenter study; urinary tract infection; daunorubicin; thrombocyte count; mental disease; sepsis; open study; 5 aza 2' deoxycytidine; bacteremia; geriatric patient; mycosis; azacitidine; parallel design; philadelphia 1 chromosome; leukemia remission; antileukemic agent; post treatment survival; faintness; cpx 351; human; male; female; priority journal; article |
| Journal Title: | Blood |
| Volume: | 123 |
| Issue: | 21 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2014-05-22 |
| Start Page: | 3239 |
| End Page: | 3246 |
| Language: | English |
| DOI: | 10.1182/blood-2013-12-540971 |
| PROVIDER: | scopus |
| PUBMED: | 24687088 |
| PMCID: | PMC4624448 |
| DOI/URL: | |
| Notes: | Blood -- Cited By (since 1996):1 -- Export Date: 8 July 2014 -- CODEN: BLOOA -- Source: Scopus |
