Abstract
We conducted a phase I study using midostaurin (25 or 50 mg orally twice daily), all-trans retinoic acid (ATRA) and CLAG chemotherapy to target multiple pathways in relapsed/refractory AML. 10 patients received the combination and no dose-limiting toxicities were observed. Two patients (22 %) achieved complete remission and 1 patient (11 %) achieved complete remission with incomplete count recovery. Pharmacokinetic data showed that the 25 mg dosing of midostaurin achieved therapeutic levels with no significant interaction between midostaurin and ATRA. With evidence of activity of ATRA in NPM1-mutated AML and midostaurin in FLT3-ITD AML, this combination warrants further investigation.
Trial registration:
ClinicalTrials.gov NCT01161550.
MeSH terms
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Adult
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Aged
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Cladribine / administration & dosage
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Cytarabine / administration & dosage
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Female
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Granulocyte Colony-Stimulating Factor / administration & dosage
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Humans
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Leukemia, Myeloid, Acute / blood
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Leukemia, Myeloid, Acute / drug therapy*
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Leukemia, Myeloid, Acute / genetics
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Male
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Middle Aged
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Mutation
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Nuclear Proteins / genetics
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Nucleophosmin
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Recurrence
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Remission Induction
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Staurosporine / administration & dosage
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Staurosporine / analogs & derivatives*
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Treatment Outcome
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Tretinoin / administration & dosage*
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fms-Like Tyrosine Kinase 3 / genetics
Substances
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NPM1 protein, human
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Nuclear Proteins
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Cytarabine
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Nucleophosmin
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Granulocyte Colony-Stimulating Factor
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Cladribine
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Tretinoin
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FLT3 protein, human
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fms-Like Tyrosine Kinase 3
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Staurosporine
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midostaurin
Associated data
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ClinicalTrials.gov/NCT01161550