Phase I/II study on cytarabine and idarubicin combined with escalating doses of clofarabine in newly diagnosed patients with acute myeloid leukaemia and high risk for induction failure (AMLSG 17-10 CIARA trial)

Br J Haematol. 2018 Oct;183(2):235-241. doi: 10.1111/bjh.15546.

Abstract

This open-label, multicentre phase I/II study determined the maximum tolerated dose (MTD), safety and efficacy of clofarabine administered with cytarabine and idarubicin in newly diagnosed acute myeloid leukaemia (AML) patients lacking favourable genetic aberrations. The MTD was 30 mg/m2 clofarabine for patients below and above 60 years. The most frequently reported grade 3-4 non-haematological adverse events were infectious and gastrointestinal toxicities. Complete remission (CR)/CR with incomplete recovery rate was 67%. Allogeneic haematopoietic cell transplantation in first remission was feasible in a high proportion of younger AML patients and probably contributed to the favourable outcome compared to historical controls.

Keywords: acute myeloid leukaemia; clofarabine; cytarabine; idarubicin; maximum tolerated dose.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Clofarabine / administration & dosage
  • Clofarabine / adverse effects
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Idarubicin / administration & dosage
  • Idarubicin / adverse effects
  • Induction Chemotherapy / methods
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Remission Induction

Substances

  • Cytarabine
  • Clofarabine
  • Idarubicin