Eisai Corporation of North America has announced data from a Phase II trial evaluating a five-day dosing regimen of Dacogen(R) (decitabine for injection) in acute myeloid leukemia (AML), the most common form of leukemia.
The study involved elderly patients with AML, who often have limited options due to comorbidities and are typically considered ineligible for standard induction chemotherapy. These data were presented today at the American Society of Hematology (ASH) 50th Annual Meeting.
Dacogen(R) is indicated for treatment of patients with myelodysplastic syndromes (MDS), including those with refractory anemia with excess blasts (immature or unformed blood cells) in transformation (RAEB-T - now re-classified by World Health Organization [WHO] as AML). Phase II and III clinical trials evaluating Dacogen(R) in patients with AML are currently underway.
Data from the Phase II study reported a complete response rate of 24 percent. A complete response designation requires that the patient have less than 5 percent blasts in the marrow, no evidence of disease outside of the bone marrow and absolute neutrophil and platelet counts of more than 1,000/uL and 100,000/uL, respectively. The majority of patients in the trial had intermediate or poor risk cytogenetics (bone marrow tests to identify abnormal chromosomes), which are associated with poor prognoses. Responses were observed across all patients including those with poor risk cytogenetics, those whose AML transformed from MDS, or those who developed AML after previous treatment for cancer. The results presented at ASH provide additional support for the ongoing investigation of Dacogen(R) in a Phase III trial currently underway in elderly patients with AML.
"We are enthusiastic about these new data presented at ASH and look forward to seeing results from our ongoing, global Phase III trial evaluating Dacogen in elderly AML patients," said Edward B. Rubenstein, MD, senior vice president, medical affairs, Oncology & Institutional Care Business Unit, Eisai Inc. "The data presented today support our commitment to continue to evaluate Dacogen as a treatment option for elderly patients with AML."
Study Details
The primary objective of this multi-center, open-label, Phase II trial was to establish the morphologic complete response (CR) rate. Dacogen(R) was administered intravenously over one hour for five consecutive days every four weeks at a dose of 20 mg/m2.
Of the 55 patients enrolled in the trial, most patients had intermediate (53 percent) or poor (42 percent) risk cytogenetics, which are associated with a poor prognosis. According to the AML response criteria, the expert-reviewed overall response rate in the intent-to-treat (ITT) population was 26 percent, with morphologic CR in 24 percent of patients and CR with incomplete blood count recovery (CRi) in 2 percent. The median time to response was three months, and responses were seen in all subgroups of patients, including patients with the poorest prognoses. Additionally, 44 percent of patients maintained stable disease during a median five cycles of therapy.
"AML is a difficult-to-treat blood cancer, particularly in elderly patients who cannot endure the toxic side effects of standard induction chemotherapy," said lead investigator, Amanda Cashen, MD, assistant professor, Washington University School of Medicine. "These data indicate that further trials are warranted in this elderly population and we look forward to seeing additional Dacogen results reported."
Besides myelosuppression, the most commonly reported adverse events considered possibly related to decitabine treatment were febrile neutropenia, fatigue, pneumonia, sepsis, dyspnea and bacteraemia.
The five-day dosing regimen of Dacogen(R) is currently being further evaluated in a global, Phase III survival study in elderly patients with AML.
About Acute Myeloid Leukemia (AML)