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Karp JE, Garrett-Mayer E, Estey EH, et al. 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. Haematologica. 2012;97(11):1736-42doi: 10.3324/haematol.2012.062539.
Karp, J. E., Garrett-Mayer, E., Estey, E. H., Rudek, M. A., Smith, B. D., Greer, J. M., Drye, D. M., Mackey, K., Dorcy, K. S., Gore, S. D., Levis, M. J., McDevitt, M. A., Carraway, H. E., Pratz, K. W., Gladstone, D. E., Showel, M. M., Othus, M., Doyle, L. A., Wright, J. J., & Pagel, J. M. (2012). 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. Haematologica, 97(11), 1736-42. https://doi.org/10.3324/haematol.2012.062539
Karp, Judith E, et al. "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." Haematologica vol. 97,11 (2012): 1736-42. doi: https://doi.org/10.3324/haematol.2012.062539
Karp JE, Garrett-Mayer E, Estey EH, Rudek MA, Smith BD, Greer JM, Drye DM, Mackey K, Dorcy KS, Gore SD, Levis MJ, McDevitt MA, Carraway HE, Pratz KW, Gladstone DE, Showel MM, Othus M, Doyle LA, Wright JJ, Pagel JM. 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. Haematologica. 2012 Nov;97(11):1736-42. doi: 10.3324/haematol.2012.062539. Epub 2012 Jun 24. PMID: 22733022; PMCID: PMC3487449.
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Haematologica. 2012 Nov;97(11):1736-42. doi: 10.3324/haematol.2012.062539. Epub 2012 Jun 24.

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.

Haematologica

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

Affiliations

  1. Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21231-1000, USA. [email protected]

PMID: 22733022 PMCID: PMC3487449 DOI: 10.3324/haematol.2012.062539

Abstract

BACKGROUND: 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.

DESIGN AND METHODS: We compared bolus flavopiridol (50 mg/m(2)/day, Arm A) versus 'hybrid' flavopiridol (30 mg/m(2) over 30 min followed by 40 mg/m(2) 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.

RESULTS: 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.

CONCLUSIONS: 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 versus conventional induction therapy for patients aged 70 years and under with intermediate or poor-risk acute myelogenous leukemia. This study is registered at www.clinicaltrials.gov as #NCT 00407966.

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