A new drug for patients with acute myeloid leukemia (AML) with a specific genetic mutation has shown surprising promise in a phase II clinical trial. For more than a third of the participants, the leukemia was completely cleared from the bone marrow. As a result, many of these patients were able to undergo potentially curative bone marrow transplants. Many of the patients who did well on the new drug, quizartinib or AC220, had failed to respond to prior therapies.

“We can put two-thirds to three-quarters of adults with AML into remission with chemotherapy, but there’s a 50% chance of the disease coming back, which usually ends up being fatal,” said lead investigator Mark Levis, MD, PhD, of Johns Hopkins Kimmel Cancer Center. “Many patients in this trial were able to go on to receive a potentially life-saving bone marrow transplant. It caught us by surprise how well it works.”

The clinical trial enrolled 137 patients with AML, and the majority of them had a mutation in the FLT3-ITD gene within their leukemia cells. An enzyme is produced by the FLT3 gene that signals bone marrow cells to divide and replenish. Approximately one quarter of patients with AML have a mutated FLT3, such that the enzyme stays on permanently, leading to rapid growth of leukemia cells and making the condition harder to treat. Quizartinib blocks the FLT3 enzyme, and it is so potent that it starts working in just 2 days, though it can take up to 60 days to completely eliminate AML cells from the bone marrow.

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Of the 99 participants with an FLT3-ITD mutation, 44% had some form of complete remission, which was typically one in which the leukemia was cleared from the bone marrow but blood and platelet transfusions were still needed. Of the 38 participants without a detectable FLT3-ITD mutation, 4% (13 patients) experienced this type of response.

The most common side effects with quizartinib were nausea (38%), anemia (29%), QT prolongation (26%), vomiting (26%), febrile neutropenia (25%), diarrhea (20%), and fatigue (20%). Fourteen patients (10%) experienced side effects severe enough to discontinue taking the drug. Investigators have been testing lower doses of the medication since the trial to reduce side effects, according to Levis.

Though long-term survival from the therapy is still unknown, of the group of 137 patients, 47 (34%) were able to receive a transplant after responding to quizartinib. Some of these patients have survived 2 years after treatment with no disease recurrence.

These results have led Ambit Biosciences, who makes the drug, to plan larger phase III trials. This study was presented at the American Society of Hematology annual meeting in Atlanta, Georgia, December 8-11, 2012.