A Phase 1 study of imatinib mesylate in combination with cytarabine and daunorubicin for c-kit positive relapsed acute myeloid leukemia

The c-kit receptor is expressed in 95% of relapsed acute myeloid leukemias (AMLs) and mediates leukemic proliferation. We conducted a Phase 1 study of the c-kit inhibitor, imatinib mesylate (IM), in combination with cytarabine and daunorubicin (7 + 3) in c-kit+ relapsed AML. IM was dose escalated using a 3 by 3 design. Phosphorylated STAT5 was absent to minimally present in residual blasts on day 14 bone marrows. The maximum tolerated dose of IM was 300 mg. The dose-limiting toxicity was Grade 3–4 hepatic toxicity. The CR/CRp rate was 57%. Cytotoxic therapy that includes IM for relapsed AML is well-tolerated and effective.