Randomized phase II study of two schedules of flavopiridol given as timed sequential therapy with cytosine arabinoside and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia.

Publication Type:

Journal Article

Source:

Haematologica (2012)

Keywords:

2012, Center-Authored Paper, Clinical Research Division, July 2012, Public Health Sciences Division

Abstract:

Background. Flavopiridol is a protein bound, cytotoxic, cyclin dependent kinase inhibitor. A Phase II trial of flavopiridol followed by ara-C and mitoxantrone (FLAM) with flavopiridol given by one hour bolus for adults with newly-diagnosed, poor-risk acute myelogenous leukemia (AML) yielded 67% complete remission (CR) with median disease-free survival (DFS) 13.6 months. Design and Methods. We compared FLAM using bolus flavopiridol (50 mg/m2/day, Arm A) vs. "hybrid" flavopiridol (30 mg/m2 over 30 minutes followed by 40 mg/m2 over 4 hours, Arm B) in 78 patients (39 per arm) with newly diagnosed, poor-risk AML. To mitigate imbalance, patients were stratified by presence or absence of secondary AML and therapy for antecedent disorder. Results. Death < day 60 occurred in 8% per arm. CR+CR with incomplete recovery (CRi) was 68% (A, 62%; B, 74%). CR+CRi rates were > 65% in both arms for patients with secondary AML and AML with adverse genetics. 91% A and 86% B received chemotherapy and/or allogeneic transplantation in CR. Median OS for CR+CRi patients has not been reached for either arm, with median DFS 13.6 months for A and 12.0 months for B. Conclusions. Both FLAM schedules produce comparably encouraging results in adults with poor-risk AML. Given the greater ease of bolus administration, we are conducting a randomized Phase II study of bolus FLAM vs. conventional induction therapy for patients < 70 years with intermediate or poor-risk AML. This study is registered at www.clinicaltrials.gov as #NCT 00407966.