A phase I trial of the aurora kinase inhibitor , ENMD-2076, in patients with relapsed or refractory acute myeloid leukemia or chronic myelomonocytic leukemia

Summary ENMD-2076 is a novel, orally-active molecule that inhibits Aurora A kinase, as well as c-Kit, FLT3 and VEGFR2. A phase I study was conducted to determine the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and toxicities of ENMD-2076 in patients with acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML). Patients received escalating doses of ENMD-2076 administered orally daily [225 mg (n = 7), 375 mg (n = 6), 325 mg (n = 9), or 275 mg (n = 5)]. Twenty-seven patients were treated (26 AML; 1 CMML-2). The most common non-hematological toxicities of any grade, regardless of association with drug, were fatigue, diarrhea, dysphonia, dyspnea, hypertension, constipation, and abdominal pain. Dose-limiting toxicities (DLTs) consisted of grade 3 fatigue, grade 3 typhilitis, grade 3 syncope and grade 3 QTc prolongation). Of the 16 evaluable patients, one patient achieved a complete remission with incomplete count recovery (CRi), three experienced a morphologic leukemia-free state (MLFS) with a major hematologic improvement in platelets (HI-P), and 5 other patients had a reduction in marrow blast percentage (i.e. 11–65 %). The RP2D in this patient population is 225 mg orally once daily.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Source: Malaysian Journal of Pathology - Category: Pathology Tags: Malays J Pathol Source Type: research
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Source: Malaysian Journal of Pathology - Category: Pathology Tags: Malays J Pathol Source Type: research
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Source: Malaysian Journal of Pathology - Category: Pathology Tags: Malays J Pathol Source Type: research
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Source: Malaysian Journal of Pathology - Category: Pathology Tags: Malays J Pathol Source Type: research
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Source: Kidney International - Category: Urology & Nephrology Authors: Tags: Commentary Source Type: research
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Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Adolescents Source Type: news
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Source: Surgery (Oxford) - Category: Surgery Source Type: research
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