A phase 1/2 study of NS-87/CPX-351 (cytarabine and daunorubicin liposome) in Japanese patients with high-risk acute myeloid leukemia

Kensuke Usuki; Toshihiro Miyamoto; Takuji Yamauchi; Kiyoshi Ando; Yoshiaki Ogawa; Masahiro Onozawa; Takahiro Yamauchi; Hitoshi Kiyoi; Akira Yokota; Takayuki Ikezoe; Yuna Katsuoka; Satoru Takada; Nobuyuki Aotsuka; Yasuyoshi Morita; Takayuki Ishikawa; Noboru Asada; Shuichi Ota; Atsushi Dohi; Kensaku Morimoto; Shunji Imai; Umi Kishimoto; Koichi Akashi; Yasushi Miyazaki; Study Group for NS-87/CPX-351

doi:10.1007/s12185-024-03733-z

A phase 1/2 study of NS-87/CPX-351 (cytarabine and daunorubicin liposome) in Japanese patients with high-risk acute myeloid leukemia

Int J Hematol. 2024 Jun;119(6):647-659. doi: 10.1007/s12185-024-03733-z. Epub 2024 Mar 26.

Authors

Kensuke Usuki¹, Toshihiro Miyamoto², Takuji Yamauchi³, Kiyoshi Ando^{4

5}, Yoshiaki Ogawa⁴, Masahiro Onozawa⁶, Takahiro Yamauchi⁷, Hitoshi Kiyoi⁸, Akira Yokota⁹, Takayuki Ikezoe¹⁰, Yuna Katsuoka¹¹, Satoru Takada¹², Nobuyuki Aotsuka¹³, Yasuyoshi Morita¹⁴, Takayuki Ishikawa¹⁵, Noboru Asada¹⁶, Shuichi Ota¹⁷, Atsushi Dohi¹⁸, Kensaku Morimoto¹⁹, Shunji Imai²⁰, Umi Kishimoto¹⁸, Koichi Akashi³, Yasushi Miyazaki²¹; Study Group for NS-87/CPX-351

Collaborators

Affiliations

¹ Department of Hematology, NTT Medical Center Tokyo, 5-9-22 Higashi-Gotanda, Shinagawa-Ku, Tokyo, 141-8625, Japan. [email protected].
² Department of Hematology, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.
³ Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan.
⁴ Department of Hematology and Onclogy, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
⁵ Department of Hematology, Hiroshima University School of Medicine, Hiroshima, Japan.
⁶ Department of Hematology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
⁷ Department of Hematology and Oncology, University of Fukui, Fukui, Japan.
⁸ Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
⁹ Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Japan.
¹⁰ Department of Hematology, Fukushima Medical University, Fukushima, Japan.
¹¹ Department of Hematology, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan.
¹² Department of Hematology, Saiseikai Maebashi Hospital, Maebashi, Gunma, Japan.
¹³ Department of Hematology and Oncology, Japanese Red Cross Society Narita Hospital, Narita, Chiba, Japan.
¹⁴ Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Sayama, Osaka, Japan.
¹⁵ Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan.
¹⁶ Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan.
¹⁷ Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Hokkaido, Japan.
¹⁸ Clinical Development Department, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
¹⁹ Data Science Depertment, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
²⁰ Drug Metabolism and Pharmacokinetics Research Department, Nippon Shinyaku Co., Ltd, Kyoto, Japan.
²¹ Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.

Abstract

Objectives: NS-87/CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. NS-87/CPX-351 exerts antileukemic action by maintaining a synergistic molar ratio of cytarabine to daunorubicin of 5:1 within the liposome while in circulation. Patients with high-risk acute myeloid leukemia (AML), which includes therapy-related AML and AML with myelodysplasia-related changes (AML-MRC), have poorer outcomes than those with other AML.

Methodology: This open-label phase 1/2 (P1/2) study was conducted in 47 Japanese patients aged 60-75 years with newly diagnosed high-risk AML to evaluate the pharmacokinetics, safety, and efficacy of NS-87/CPX-351.

Results: In the 6 patients enrolled in the P1 portion, no dose-limiting toxicities (DLTs) were reported, and 100 units/m² during the induction cycle was found to be acceptable. Cytarabine and daunorubicin had a long half-life in the terminal phase (32.8 and 28.7 h, respectively). In the 35 patients enrolled in the P2 portion, composite complete remission (CRc; defined as complete remission [CR] or CR with incomplete hematologic recovery [CRi]) was achieved in 60.0% (90% CI: 44.7-74.0) of the patients. Adverse events due to NS-87/CPX-351 were well tolerated.

Outcomes: NS-87/CPX-351 can be considered as a frontline treatment option for Japanese patients with high-risk AML.

Keywords: Acute myeloid leukemia; CPX-351; Cytarabine; Daunorubicin; Liposomal formulation.

Publication types

Clinical Trial, Phase I
Clinical Trial, Phase II
Multicenter Study

MeSH terms

Aged
Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
Antineoplastic Combined Chemotherapy Protocols* / adverse effects
Antineoplastic Combined Chemotherapy Protocols* / pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
Asian People
Cytarabine* / administration & dosage
Cytarabine* / pharmacokinetics
Daunorubicin* / administration & dosage
Daunorubicin* / pharmacokinetics
East Asian People
Female
Humans
Japan
Leukemia, Myeloid, Acute* / drug therapy
Liposomes*
Male
Middle Aged
Treatment Outcome

Substances

Daunorubicin
Cytarabine
Liposomes
CPX-351