Phase I study of alvocidib plus cytarabine/mitoxantrone or cytarabine/daunorubicin for acute myeloid leukemia in Japan

Takayuki Ikezoe, Kiyoshi Ando, Masahiro Onozawa, Takahisa Yamane, Naoko Hosono, Yasuyoshi Morita, Toru Kiguchi, Hiromi Iwasaki, Toshihiro Miyamoto, Keisuke Matsubara, Saori Sugimoto, Yasushi Miyazaki, Masahiro Kizaki, Koichi Akashi

Research output: Contribution to journalArticlepeer-review


Therapeutic improvements are needed for patients with acute myeloid leukemia (AML), particularly those who have relapsed or who have treatment-refractory (R/R) AML or newly diagnosed patients with poor prognostic factors. Alvocidib (DSP-2033), a potent cyclin-dependent kinase 9 inhibitor, has previously demonstrated promising clinical activity for the treatment of AML. In this multicenter, open-label, uncontrolled, 3 + 3 phase I study, we investigated the safety and tolerability of alvocidib administered in combination with either cytarabine and mitoxantrone (ACM) for R/R AML or cytarabine/daunorubicin (A + 7 + 3) for newly diagnosed AML. Alvocidib was administered to all patients as a 30-min intravenous (i.v.) bolus (30 mg/m2/d), followed by a continuous i.v. infusion over 4 h on days 1–3 (60 mg/m2/d). A total of 10 patients were enrolled: six received ACM (at two dose levels of cytarabine and mitoxantrone) and four received A + 7 + 3. Alvocidib was tolerated and no dose-limiting toxicities were observed. All patients experienced adverse events, of which diarrhea was the most frequent (100%); hematologic events were also common. Alvocidib concentration peaked at the end of dosing (4.5 h after start of administration), plasma accumulation after repeated dosing was minimal and urinary excretion was negligible. The rate of complete remission/complete remission with incomplete hematologic recovery was 66.7% with the ACM regimen in R/R AML, including four complete remission (median duration 13.6 months), and 75% (three complete remission) with the A + 7 + 3 regimen. Further development of alvocidib in hematologic malignancies is warranted. The trial is registered with, NCT03563560.

Original languageEnglish
Pages (from-to)4258-4266
Number of pages9
JournalCancer Science
Issue number12
Publication statusPublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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