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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

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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. / Fiedler, Walter; Kayser, Sabine; Kebenko, Maxim; Janning, Melanie; Krauter, Jürgen; Schittenhelm, Marcus; Götze, Katharina; Weber, Daniela; Göhring, Gudrun; Teleanu, Veronica; Thol, Felicitas; Heuser, Michael; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Schlenk, Richard F.

In: BRIT J HAEMATOL, 29.03.2015.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Fiedler, W, Kayser, S, Kebenko, M, Janning, M, Krauter, J, Schittenhelm, M, Götze, K, Weber, D, Göhring, G, Teleanu, V, Thol, F, Heuser, M, Döhner, K, Ganser, A, Döhner, H & Schlenk, RF 2015, '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', BRIT J HAEMATOL. https://doi.org/10.1111/bjh.13353

APA

Fiedler, W., Kayser, S., Kebenko, M., Janning, M., Krauter, J., Schittenhelm, M., Götze, K., Weber, D., Göhring, G., Teleanu, V., Thol, F., Heuser, M., Döhner, K., Ganser, A., Döhner, H., & Schlenk, R. F. (2015). 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. BRIT J HAEMATOL. https://doi.org/10.1111/bjh.13353

Vancouver

Fiedler W, Kayser S, Kebenko M, Janning M, Krauter J, Schittenhelm M et al. 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. BRIT J HAEMATOL. 2015 Mar 29. https://doi.org/10.1111/bjh.13353

Bibtex

@article{b4e052eddc8342f5a2c2b0e143715dbc,
title = "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",
abstract = "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 survival, relapse-free and 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.",
author = "Walter Fiedler and Sabine Kayser and Maxim Kebenko and Melanie Janning and J{\"u}rgen Krauter and Marcus Schittenhelm and Katharina G{\"o}tze and Daniela Weber and Gudrun G{\"o}hring and Veronica Teleanu and Felicitas Thol and Michael Heuser and Konstanze D{\"o}hner and Arnold Ganser and Hartmut D{\"o}hner and Schlenk, {Richard F}",
note = "{\textcopyright} 2015 John Wiley & Sons Ltd.",
year = "2015",
month = mar,
day = "29",
doi = "10.1111/bjh.13353",
language = "English",
journal = "BRIT J HAEMATOL",
issn = "0007-1048",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - 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

AU - Fiedler, Walter

AU - Kayser, Sabine

AU - Kebenko, Maxim

AU - Janning, Melanie

AU - Krauter, Jürgen

AU - Schittenhelm, Marcus

AU - Götze, Katharina

AU - Weber, Daniela

AU - Göhring, Gudrun

AU - Teleanu, Veronica

AU - Thol, Felicitas

AU - Heuser, Michael

AU - Döhner, Konstanze

AU - Ganser, Arnold

AU - Döhner, Hartmut

AU - Schlenk, Richard F

N1 - © 2015 John Wiley & Sons Ltd.

PY - 2015/3/29

Y1 - 2015/3/29

N2 - 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 survival, relapse-free and 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.

AB - 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 survival, relapse-free and 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.

U2 - 10.1111/bjh.13353

DO - 10.1111/bjh.13353

M3 - SCORING: Journal article

C2 - 25818407

JO - BRIT J HAEMATOL

JF - BRIT J HAEMATOL

SN - 0007-1048

ER -