CAMBRIDGE, Mass., June 2 Genzyme Corp.(Nasdaq: GENZ) reported preliminary data today from a fully-enrolled pivotal,phase 2 study examining the safety and effectiveness of Clolar(R)(clofarabine) as a single agent in previously untreated, older adult patientswith acute myelogenous leukemia (AML) who are unlikely to benefit fromconventional "7+3" anthracycline plus cytarabine-based induction chemotherapy.
Results from the CLASSIC-II clinical trial show that patients withunfavorable prognostic factors who received single agent clofarabine exhibiteda 45 percent overall remission rate based on investigator assessment, withmanageable treatment-related side effects. Importantly, the 30 day all-causemortality, one of the secondary endpoints in this study, was only 9.6 percent,which compares favorably to existing treatment options. Data from the studywere presented at the annual meeting of the American Society of ClinicalOncology (ASCO) in Chicago.
"The therapeutic outcomes for older AML patients have not improved in thepast thirty years," stated Mark J. Enyedy, president of Genzyme Oncology, abusiness unit of Genzyme Corporation. "These data highlight the potential ofclofarabine to become an innovative and much needed treatment option for thesepatients. We look forward to submitting a supplemental new drug applicationin the United States later this year to expand the current product label intofront-line therapy for adult AML and to make a similar filing in Europe aroundthis same time."
As reported at ASCO, investigator-assessed response data show a 45 percentoverall remission rate among patients treated with single agent clofarabine,with 40 percent of patients achieving a complete remission to therapy and 5percent attaining a complete remission with incomplete platelet recovery.Overall remission in this study is defined as a patient achieving eithercomplete remission or complete remission with incomplete platelet recovery.Secondary endpoints include duration of remission, disease free survival,overall survival, safety and thirty-day mortality. The CLASSIC II study dataare based on clinical responses from 115 patients at 20 sites in the U.S.
Data also show overall remission rates of 50 percent among patients withprior blood disorders; 43 percent in patients with adverse cytogenetics; 40percent in patients 70 years of age and older; and 38 percent in patients withan ECOG performance status of 2. Remission rates in patients with up to threepre-defined risk factors required for study enrollment also exceeded 40percent.
The study also demonstrated that the toxicity profile of clofarabine waspredictable and manageable. Drug-related adverse events occurring in morethan 15 percent of patients included nausea, febrile neutropenia, vomiting,diarrhea and rash; most were grade 1 or 2. As expected, Grade 4 neutropeniaand thrombocytopenia occurred in a majority of patients. Only five of 115patients discontinued treatment due to an adverse event or toxicity precludingfurther therapy. The study has completed enrollment and patients are beingfollowed for remission duration, disease-free survival and overall survival.An independent panel of hematologists and hematopathologists are confirmingthe investigators' assessment of responses.
"In addition to the excellent overall safety and efficacy findings we areobserving with single agent clofarabine, we also see impressive responses inolder patients with poor prognostic cytogenetic abnormalities when treatedwith the drug," stated Harry P. Erba, MD, Ph.D., University of Michigan, oneof the co-principal investigators for this study. "This study helps to definea new approach to treatment for patients unlikely to benefit from conventional7+3 induction chemotherapy and provides support for the importance ofassessing cytogenetics prior to induction treatment."