Phase 1/2 clinical study of dasatinib in Japanese patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia

Int J Hematol. 2009 Apr;89(3):332-341. doi: 10.1007/s12185-009-0260-2. Epub 2009 Mar 5.

Abstract

A phase 1/2 study was conducted to assess the safety and efficacy of dasatinib in Japanese patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) resistant or intolerant to imatinib. In phase 1, 18 patients with chronic phase (CP) CML were treated with dasatinib 50, 70, or 90 mg twice daily to evaluate safety. Dasatinib <or= 90 mg twice daily was well tolerated. In phase 2, dasatinib 70 mg was given twice daily to CP-CML patients for 24 weeks and to CML patients in accelerated phase (AP)/blast crisis (BC) or Ph(+) ALL for 12 weeks. In the CP-CML group (n = 30) complete hematologic response was 90% and major cytogenetic response (MCyR) 53%. In the AP/BC-CML group (n = 11) major hematologic response (MaHR) was 64% and MCyR 27%, whereas in the Ph(+) ALL group (n = 13) MaHR was 38% and MCyR 54%. Dasatinib was well tolerated and most of the nonhematologic toxicities were mild or moderate. Dasatinib therapy resulted in high rates of hematologic and cytogenetic response, suggesting that dasatinib is promising as a new treatment for Japanese CML and Ph(+) ALL patients resistant or intolerant to imatinib.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Asian People
  • Dasatinib
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / genetics
  • Leukemia, Myeloid, Chronic-Phase / metabolism
  • Middle Aged
  • Mutation / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use*
  • Thiazoles / adverse effects
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Thiazoles
  • Fusion Proteins, bcr-abl
  • Dasatinib