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Acute myeloid leukemia

Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality

Leukemia volume 34, pages 2914–2924 (2020)Cite this article

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Abstract

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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Fig. 1: Trial consort.
Fig. 2: Risk factors for induction mortality.
Fig. 3: Kaplan–Meier survival curves for event-free survival (EFS) and overall survival (OS).
Fig. 4: Change in ejection fraction pre and post-treatment with CPX-351.

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Acknowledgements

GCI received funding through the K12 Paul Calabresi Clinical Scholarship Award (NIH/NCI K12 CA088084).

Funding

The study was supported in part by Celator/Jazz, and by the Cancer Center Support Grant (NCI Grant P30 CA016672).

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Authors and Affiliations

  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ghayas C. Issa, Hagop M. Kantarjian, Yesid Alvarado, Gautam Borthakur, Naval Daver, Courtney D. DiNardo, Elias Jabbour, Prithviraj Bose, Nitin Jain, Tapan M. Kadia, Kiran Naqvi, Naveen Pemmaraju, Koichi Takahashi, Srdan Verstovsek, Micheal Andreeff, Steven M. Kornblau, Zeev Estrov, Alessandra Ferrajoli, Guillermo Garcia-Manero, Maro Ohanian, William G. Wierda, Farhad Ravandi & Jorge E. Cortes

  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Lianchun Xiao & Jing Ning

  3. Georgia Cancer Center, Augusta University, Augusta, GA, USA

    Jorge E. Cortes

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  1. Ghayas C. Issa
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Correspondence to Jorge E. Cortes.

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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 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.

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Issa, G.C., Kantarjian, H.M., Xiao, L. et al. Phase II trial of CPX-351 in patients with acute myeloid leukemia at high risk for induction mortality. Leukemia 34, 2914–2924 (2020). https://doi.org/10.1038/s41375-020-0916-8

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