@article{Judith E. Karp_Elizabeth Garrett-Mayer_Elihu H. Estey_Michelle A. Rudek_B. Douglas Smith_Jacqueline M. Greer_D. Michelle Drye_Karen Mackey_Kathleen Shannon Dorcy_Steven D. Gore_Mark J. Levis_Michael A. McDevitt_Hetty E. Carraway_Keith W. Pratz_Douglas E. Gladstone_Margaret M. Showel_Megan Othus_L. Austin Doyle_John J. Wright_John M. Pagel_2012, place={Pavia, Italy}, title={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}, volume={97}, url={https://haematologica.org/article/view/6475}, DOI={10.3324/haematol.2012.062539}, abstractNote={<strong>Background</strong> Flavopiridol is a protein-bound, cytotoxic, cyclin dependent kinase inhibitor. A phase II trial of flavopiridol followed by ara-C and mitoxantrone with flavopiridol given by 1-h bolus for adults with newly-diagnosed, poor-risk acute myelogenous leukemia yielded 67% complete remission with median disease-free survival of 13.6 months.<strong>Design and Methods</strong> We compared bolus flavopiridol (50 mg/m<sup>2</sup>/day, Arm A) <em>versus</em> ’hybrid’ flavopiridol (30 mg/m<sup>2</sup> over 30 min followed by 40 mg/m<sup>2</sup> over 4 h, Arm B) followed by ara-C and mitoxantrone in 78 patients (39 per arm) with newly diagnosed, poor-risk acute myelogenous leukemia. To mitigate imbalance, patients were stratified by presence or absence of secondary leukemia and therapy for antecedent disorder.<strong>Results</strong> Death at or before Day 60 occurred in 8% of patients per arm. Complete remission plus complete remission with incomplete recovery was 68% (Arm A, 62%; Arm B, 74%) overall, and 65% or over in both arms for patients with secondary leukemia and leukemia with adverse genetics. In Arm A 91% and in Arm B 86% of patients received chemotherapy and/or allogeneic transplantation in complete remission. Median overall survival for all remission patients has not been reached for either arm, with median disease free survival of 13.6 months for Arm A and of 12.0 months for Arm B.<strong>Conclusions</strong> Both flavopiridol schedules produce comparably encouraging results in adults with poor-risk acute myelogenous leukemia. Given the greater ease of bolus administration, we are conducting a randomized phase II study of bolus flavopiridol followed by ara-c and mitoxantrone <em>versus</em> conventional induction therapy for patients aged 70 years and under with intermediate or poor-risk acute myelogenous leukemia. This study is registered at <em><a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a> as #NCT 00407966</em&gt;.}, number={11}, journal={Haematologica}, author={Judith E. Karp and Elizabeth Garrett-Mayer and Elihu H. Estey and Michelle A. Rudek and B. Douglas Smith and Jacqueline M. Greer and D. Michelle Drye and Karen Mackey and Kathleen Shannon Dorcy and Steven D. Gore and Mark J. Levis and Michael A. McDevitt and Hetty E. Carraway and Keith W. Pratz and Douglas E. Gladstone and Margaret M. Showel and Megan Othus and L. Austin Doyle and John J. Wright and John M. Pagel}, year={2012}, month={Nov.}, pages={1736-1742} }