A phase I/II study of sunitinib and intensive chemotherapy in patients over 60 years of age with acute myeloid leukaemia and activating FLT3 mutations

Br J Haematol. 2015 Jun;169(5):694-700. doi: 10.1111/bjh.13353. Epub 2015 Mar 29.


Acute myeloid leukaemia (AML) with FLT3 mutation has a dismal prognosis in elderly patients. Treatment with a combination of FLT3 inhibitors and standard chemotherapy has not been extensively studied. Therefore, we instigated a phase I/II clinical trial of chemotherapy with cytosine arabinoside (Ara-C)/daunorubicin induction (7+3) followed by three cycles of intermediate-dose Ara-C consolidation in 22 AML patients with activating FLT3 mutations. Sunitinib was added at predefined dose levels and as maintenance therapy for 2 years. At dose level 1, sunitinib 25 mg daily continuously from day 1 onwards resulted in two cases with dose-limiting toxicity (DLT), prolonged haemotoxicity and hand-foot syndrome. At dose level -1, sunitinib 25 mg was restricted to days 1-7 of each chemotherapy cycle. One DLT was observed in six evaluable patients. Six additional patients were treated in an extension phase. Thirteen of 22 patients (59%; 8/14 with FLT3-internal tandem duplication and 5/8 with FLT3-tyrosine kinase domain) achieved a complete remission/complete remission with incomplete blood count recovery. For the 17 patients included at the lower dose level, median overall, relapse-free and event-free survival were 1·6, 1·0 and 0·4 years, respectively. Four out of five analysed patients with relapse during maintenance therapy lost their initial FLT3 mutation, suggesting outgrowth of FLT3 wild-type subclones.

Keywords: FLT3 mutation; acute myeloid leukaemia; elderly patients; phase I/II study; sunitinib.

Publication types

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

MeSH terms

  • Age Factors
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Humans
  • Indoles / administration & dosage
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Mutation*
  • Pyrroles / administration & dosage
  • Remission Induction
  • Sunitinib
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / genetics*


  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • fms-Like Tyrosine Kinase 3
  • Sunitinib