At Johns Hopkins and nine other centers, the 137 AML recruited patients received quizartinib at a starting dose of 90 mg/day for women and 135 mg/day for men, and were treated continuously during 28-day cycles. Study participants either had relapsed, did not respond to second-line chemotherapy or had relapsed following hematopoietic stem cell transplantation.
Forty-four percent (44) of the 99 participants with a FLT3-ITD mutation experienced some form of complete remission, typically one in which the leukemia was cleared from the bone marrow, but the patient still needed blood and platelet transfusions. Thirty-four percent (13) of the 38 participants in whom the FLT3-ITD mutation was not detectable experienced this type of response.
The most common side effects with quizartinib were nausea (38 percent), anemia (29 percent), QT prolongation (an abnormality found on an EKG; 26 percent), vomiting (26 percent), febrile neutropenia (development of fever in someone with low white blood cell count; 25 percent), diarrhea (20 percent), and fatigue (20 percent). Fourteen patients (10 percent) 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, Levis says.
Long-term survival from the therapy is still unknown, Levis says, but of the group of 137 patients, 47 (34 percent) were able to receive a transplant after responding to quizartinib. Some of these patients have survived two years after treatment with no disease recurrence.
Based on results, the company that makes the drug, Ambit Biosciences, is planning larger Phase III trials, in which patients who have the FLT3
|Contact: Vanessa Wasta|
Johns Hopkins Medicine