TY - JOUR
T1 - Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality
AU - Issa, Ghayas C.
AU - Kantarjian, Hagop M.
AU - Xiao, Lianchun
AU - Ning, Jing
AU - Alvarado, Yesid
AU - Borthakur, Gautam
AU - Daver, Naval
AU - DiNardo, Courtney D.
AU - Jabbour, Elias
AU - Bose, Prithviraj
AU - Jain, Nitin
AU - Kadia, Tapan M.
AU - Naqvi, Kiran
AU - Pemmaraju, Naveen
AU - Takahashi, Koichi
AU - Verstovsek, Srdan
AU - Andreeff, Micheal
AU - Kornblau, Steven M.
AU - Estrov, Zeev
AU - Ferrajoli, Alessandra
AU - Garcia-Manero, Guillermo
AU - Ohanian, Maro
AU - Wierda, William G.
AU - Ravandi, Farhad
AU - Cortes, Jorge E.
N1 - Funding Information:
consulting honoraria from AbbVie; Pharmacyclics; Genentech; Bristol-Myers Squibb; Pfizer; ADC Therapeutics; AstraZeneca; Servier; Cellectis; Verastem; Precision Biosciences; Adaptive. NP received research funding from Stemline; Novartis; Abbvie; Samus; Cellectis; Plexxikon; Daiichi-Sankyo; Affymetrix; and received consulting honoraria from Celgene; Stemline; Incyte; Novartis; MustangBio; Roche Di, LFB. KT received research funding from Onconova; MEI, served on an advisory board for Symbio Pharmaceuticals; GSK; Celgene and received honoraria from Dava Oncology; Kyowa Hakko Kirin. MA received research funding from Daiichi Sankyo, Inc.; Jazz; and consultancy honoraria from Jazz; Celgene; Amgen; AstaZeneca; Dimensions Capital; and equity ownership from Reata; Aptose; Europics; Senti Bio; Oncoceutics; Oncolyze. FR received research funding from Amgen, Bristol-Myers Squibb, Merck, Seattle Genetics, Sunesis Pharmaceuticals; Pfizer; and honoraria for consulting or advisory role for Jazz; Amgen; Seattle Genetics; Sunesis Pharmaceuticals. JEC received research funding (to the institution while at the MD Anderson) and consulting honoraria from Celator/ Jazz, Novartis, Daiichi, Astellas, Daiichi, Merus, Immunogen, Biopath Holdings.
Funding Information:
Conflict of interest GCI received research funding from Celgene and served on an advisory board for Novartis. HMK received research funding from Ariad; Astex; Bristol-Myers Squibb; Cyclacel; Daiichi-Sankyo; Pfizer; Immunogen; Jazz; Novartis and honoraria from Pfizer; Immunogen; Actinium and Takeda. YA received research funding from Jazz and honoraria from Abbott. GB received research funding from AbbVie; Incyte; Janssen; Cyclacel; BioLine Rx; NKarta: and consulting honoraria from BioLine Rx; NKarta; PTC Therapeutics; Oncoceutics, Inc. ND received research funding from Sunesis Pharmaceuticals, Inc.; Karyopharm; Immunogen; Pfizer; Incyte; Bristol-Myers Squibb; Daiichi-Sankyo; Kiromic and consulting honoraria from Sunesis Pharmaceuticals, Inc.; Karyopharm; Pfizer; Incyte; Bristol-Myers Squibb; Novartis; Otsuka America Pharmaceutical, Inc. CDD received research funding from Agios; Novartis; Celgene; Daiichi-Sankyo; Calithera Biosciences and consulting honoraria from AbbVie; Agios; Novartis; Celgene; Daiichi-Sankyo; Jazz; Notable Laboratories and is a Scientific Advisory Board member of Notable Laboratories. PB received research funding from Incyte; Celgene; CTI BioPharma; Blueprint Medicines; Constellation Pharmaceuticals; Kartos Therapeutics; Astellas; Pfizer; NS Pharma; Promedior and consulting honoraria from Incyte; Celgene; CTI BioPharma; Blueprint Medicines; Kartos Therapeutics. NJ received research funding and
Funding Information:
Funding The study was supported in part by Celator/Jazz, and by the Cancer Center Support Grant (NCI Grant P30 CA016672).
Funding Information:
Acknowledgements GCI received funding through the K12 Paul Calabresi Clinical Scholarship Award (NIH/NCI K12 CA088084).
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - CPX-351 is a liposomal formulation of cytarabine/daunorubicin with a 5:1 fixed molar ratio. We investigated the safety and efficacy of escalating doses of CPX-351 in patients with acute myeloid leukemia (AML) at high risk of induction mortality with standard chemotherapy determined through assessment of leukemia and patient-related risk factors for intensive chemotherapy in an open-label, phase II trial. Patients were randomized to receive 50 or 75 units/m2 on days 1, 3, and 5. Once safety was established, a 100 units/m2 arm was opened. Fifty-six patients were enrolled, 16, 24, and 16 in the 50, 75, and 100 units/m2 arms, respectively. The composite complete remission rate (complete remission + complete remission with incomplete blood count recovery) was lowest with 50 units/m2 (19%) compared with 75 units/m2 (38%) and 100 units/m2 (44%) (P = 0.35). The 50 units/m2 arm had a median OS of 4.3 months, compared with 8.6 and 6.2 months for the 75 and 100 units/m2 respectively (P = 0.04). Nonhematologic grade 3/4 treatment-emergent adverse events included febrile neutropenia (34%), pneumonia (23%), and sepsis (16%). CPX-351 at 75 units/m2 has favorable safety and efficacy for AML patients at high risk of induction mortality with some tolerating the standard dose of 100 units/m2.
AB - CPX-351 is a liposomal formulation of cytarabine/daunorubicin with a 5:1 fixed molar ratio. We investigated the safety and efficacy of escalating doses of CPX-351 in patients with acute myeloid leukemia (AML) at high risk of induction mortality with standard chemotherapy determined through assessment of leukemia and patient-related risk factors for intensive chemotherapy in an open-label, phase II trial. Patients were randomized to receive 50 or 75 units/m2 on days 1, 3, and 5. Once safety was established, a 100 units/m2 arm was opened. Fifty-six patients were enrolled, 16, 24, and 16 in the 50, 75, and 100 units/m2 arms, respectively. The composite complete remission rate (complete remission + complete remission with incomplete blood count recovery) was lowest with 50 units/m2 (19%) compared with 75 units/m2 (38%) and 100 units/m2 (44%) (P = 0.35). The 50 units/m2 arm had a median OS of 4.3 months, compared with 8.6 and 6.2 months for the 75 and 100 units/m2 respectively (P = 0.04). Nonhematologic grade 3/4 treatment-emergent adverse events included febrile neutropenia (34%), pneumonia (23%), and sepsis (16%). CPX-351 at 75 units/m2 has favorable safety and efficacy for AML patients at high risk of induction mortality with some tolerating the standard dose of 100 units/m2.
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UR - http://www.scopus.com/inward/citedby.url?scp=85093642271&partnerID=8YFLogxK
U2 - 10.1038/s41375-020-0916-8
DO - 10.1038/s41375-020-0916-8
M3 - Article
C2 - 32546726
AN - SCOPUS:85093642271
SN - 0887-6924
VL - 34
SP - 2914
EP - 2924
JO - Leukemia
JF - Leukemia
IS - 11
ER -
