CPX-351 Receives Fast Track Designation for Relapsed AML

The Food and Drug Administration granted a Fast Track Designation to CPX-351 for the treatment of elderly patients with relapsed acute myeloid leukemia (AML).

The designation is meant to expedite the development and review of CPX-351, which encapsulates the chemotherapy drugs cytarabine and daunorubicin in a liposomal formulation.

The designation is based on the results of two phase 2 studies, the first of which examined the drug as a first-line treatment for 126 patients with newly diagnosed AML who were aged 60 to 75 years. The primary endpoint for the study was complete response. The secondary endpoints were complete response duration, overall survival (OS) and event-free survival (EFS).

The complete response rate with CPX-351 was 66.7 percent versus 51.2 percent with standard chemotherapy. Median EFS and OS were also higher in the CPX-351 arm at 6.5 versus 2.0 months and 14.7 versus 12.9 months, respectively.

Ten patients in the control arm who had persistent AML following treatment crossed over to the experimental arm and were administered CPX-351 as salvage therapy. Four of these patients had responses and the survival data for the study was potentially confounded, as all four patients were alive for more than one year.

Positive data were also observed in a planned subset analysis of patients with secondary AML. There was a 6-month, survival benefit in this subgroup (12.1 compared with 6.1 months). Event-free survival was 4.5 months with CPX-351 versus 1.3 months with standard chemotherapy.

“AML patients treated with CPX-351 had a higher likelihood of remission, without evidence of increased early mortality, than patients treated with standard chemotherapy. In addition, CPX-351 led to longer survival in the large subset of patients whose AML arose out of a previously diagnosed hematologic disorder or a history of prior cytotoxic treatment, commonly referred to as secondary AML,” said lead author Jeffrey Lancet, the leukemia section chief at the H. Lee Moffitt Cancer Center and Research Institute, in a statement.

The authors of the study concluded that CPX-351 had an acceptable safety profile. Cytopenia recovery was longer for patients receiving CPX-351, with a higher incidence of moderate to severe infections; however, there was not an accompanying increase in infection-related mortality or 60-day mortality.

The other phase 2 study examining CPX-351 included 125 patients aged 18 to 65 years with relapsed AML following an initial complete remission of at least one month. Patients were given either CPX-351 or investigators’ choice of salvage chemotherapy. The control-arm regimens typically included cytarabine and an anthracycline in combination with one or more additional drugs.

The study did not meet its primary endpoint of overall survival improvement at one-year post-treatment. However, there was a benefit with CPX-351 among the a group of patients that were considered poor-risk. A higher response rate and lower 60-day mortality rate were also observed with CPX-351 in this poor-risk subgroup.

“Patients with first relapse AML have generally a poor prognosis, with a limited likelihood of response following salvage treatment. This is particularly true for patients classified by the EPI as poor-risk upon entering the trial,” said lead investigator Jorge Cortes, deputy chair of the Department of Leukemia at The MD Anderson Cancer Center. “We were very pleased to see promising response rates in this difficult-to-treat population.”