New Drug for Myeloid Malignancies Moves to Phase II Clinical Trials

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New Rx for Myeloid Malignancies Moves to Phase II Clinical Trials
New Rx for Myeloid Malignancies Moves to Phase II Clinical Trials

(HealthDay News) — The selective Hedgehog antagonist PF-04449913 seems safe and is tolerated in adults with myeloid malignancies, according to a study published online July 26 in The Lancet Haematology.

Giovanni Martinelli, M.D., from the University of Bologna in Italy, and colleagues conducted an open-label, dose-finding, standard 3+3 design phase I study of PF-04449913 in adults with myeloid malignancies. Forty-seven patients who were refractory, resistant, or intolerant to previous treatments were enrolled from three U.S. centers and one center in Italy. Patients received once-daily PF-04449913 continuously for up to 12 28-day cycles until disease progression, unacceptable toxic effects, or patient withdrawal. The initial dose was 5 mg, and was increased by 100 percent until the first dose-limiting toxic effect (DLT); thereafter, the dose increased by 50 percent.

Two patients experienced DLTs, one each in the 80 mg and 600 mg dose groups. The researchers established the maximum tolerated dose as 400 mg once daily. Sixty percent of enrolled patients experienced treatment-related adverse events, of which three were grade 4 in severity. The most common treatment-related adverse events were dysgeusia, decreased appetite, and alopecia. There were 15 deaths, but none were treatment related. The recommended phase II dose was 200 mg or lower once daily.

"Based on these findings, PF-04449913 is being tested in phase II studies in patients with myelodysplastic syndrome, acute myeloid leukemia, and myelofibrosis," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including Pfizer, which is developing PF-04449913 and funded the study.

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