Phase I Trial of FLAGM with High Doses of Cytosine Arabinoside for Relapsed, Refractory Acute Myeloid Leukemia: Study of the Japan Adult Leukemia Study Group (JALSG)

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This study was designed to determine the optimal high dose for cytosine arabinoside (ara-C) in combination with fludarabine, granulocyte colony-stimulating factor, and mitoxantrone (FLAGM) in adult patients with relapsed or refractory acute myeloid leukemia. Nine patients were enrolled at increasing dosage levels of ara-C (8,12, and 16 g/m2 per dose level). Ara-C and fludarabine were administered once a day at level 1, once or twice a day at level 2, and twice a day at level 3. All patients had grade 4 hematologic toxicity.The most common adverse events were of grade 2 or less, with nausea and vomiting being the most common (6 events), followed by diarrhea (5 events), and rash (5 events). Of the 13 grade 3 nonhematologic toxicities reported, the 2 most common were febrile neutropenia (6 events) and disseminated intravascular coagulation (3 events). No early deaths were observed. FLAGM with high-dose ara-C was considered safe for patients, and the recommended dosage of ara-C in this study was 2 g/m2 every 12 hours for a total dose of 16 g/m2.

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Correspondence to Shuichi Miyawaki or Yasukazu Kawai or Akihiro Takeshita or Norio Komatsu or Noriko Usui or Yukihiro Arai or Fumihiro Ishida or Takeshi Morii or Yasuhiko Kano or Michinori Ogura or Noriko Doki or Ryuzo Ohno.

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Miyawaki, S., Kawai, Y., Takeshita, A. et al. Phase I Trial of FLAGM with High Doses of Cytosine Arabinoside for Relapsed, Refractory Acute Myeloid Leukemia: Study of the Japan Adult Leukemia Study Group (JALSG). Int J Hematol 86, 343–347 (2007).

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Key words

  • AML
  • Ara-C
  • FLAGM therapy
  • Cytarabine
  • High-dose ara-C
  • Phase I study