A phase 2 study of vorinostat in acute myeloid leukemia

Eric W. Schaefer, Arturo Loaiza-Bonilla, Mark Juckett, John F. DiPersio, Vivek Roy, James L Slack, Wenting Wu, Kristina Laumann, Igor Espinoza-Delgado, Steven D. Gore

Research output: Contribution to journalArticle

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Abstract

Background: This two-stage, multi-institutional, randomized phase 2 trial assessed the toxicity and response rate associated with two treatment schedules of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamic acid; SAHA) in patients with relapsed acute myeloid leukemia and in selected untreated patients with high-risk acute myeloid leukemia. Design and Methods: Patients with relapsed or untreated acute myeloid leukemia who were not candidates for chemotherapy entered one of the two treatment arms. In both arms a total dose of 8400 mg of vorinostat was delivered in each 21-day cycle of treatment: in arm A the dose regimen was 400 mg daily whereas in arm B the dose regimen was 200 mg three times daily for 14 days followed by 1 week rest. Results: Data from all 37 patients were used for the analyses. In arm A (n=15), the confirmed complete remission rate was 0% (95% CI, 0% to 23%); this arm was closed at the planned interim analysis. In arm B (n=22), the confirmed complete remission rate was 4.5% (1 response; 95% CI, 0.4% to 24%), with a duration of response exceeding 398 days. The median time to treatment failure in arm A was 42 days (95% CI, 26 to 57); although a minimum of four cycles of treatment were planned, 11 patients (79%) received no more than two cycles. The median time to treatment failure in arm B was 46 days (95% CI, 20 to 71); 13 patients (59%) received no more than two cycles of treatment. Conclusions: Vorinostat monotherapy demonstrated minimal activity in this group of patients with acute myeloid leukemia. Therapy was discontinued in many patients before the planned four cycles had been administered, either because of failure of vorinostat to control the leukocyte count or patients' and physicians' preference. Future studies of vorinostat in acute myeloid leukemia should focus on combinations with other drugs with which it might interact pharmacodynamically. ClinicalTrials.gov Identifier: NCT00305773.

Original languageEnglish (US)
Pages (from-to)1375-1382
Number of pages8
JournalHaematologica
Volume94
Issue number10
DOIs
StatePublished - Oct 2009

Fingerprint

Acute Myeloid Leukemia
Treatment Failure
Therapeutics
Histone Deacetylase Inhibitors
vorinostat
Patient Preference
Leukocyte Count
Appointments and Schedules
Physicians
Drug Therapy
Pharmaceutical Preparations

Keywords

  • Acute myeloid leukemia
  • HDAC
  • Histone deacetylase inhibitor
  • Phase 2
  • SAHA
  • Suberoylanilide hydroxamic acid
  • Vorinostat

ASJC Scopus subject areas

  • Hematology

Cite this

Schaefer, E. W., Loaiza-Bonilla, A., Juckett, M., DiPersio, J. F., Roy, V., Slack, J. L., ... Gore, S. D. (2009). A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica, 94(10), 1375-1382. https://doi.org/10.3324/haematol.2009.009217

A phase 2 study of vorinostat in acute myeloid leukemia. / Schaefer, Eric W.; Loaiza-Bonilla, Arturo; Juckett, Mark; DiPersio, John F.; Roy, Vivek; Slack, James L; Wu, Wenting; Laumann, Kristina; Espinoza-Delgado, Igor; Gore, Steven D.

In: Haematologica, Vol. 94, No. 10, 10.2009, p. 1375-1382.

Research output: Contribution to journalArticle

Schaefer, EW, Loaiza-Bonilla, A, Juckett, M, DiPersio, JF, Roy, V, Slack, JL, Wu, W, Laumann, K, Espinoza-Delgado, I & Gore, SD 2009, 'A phase 2 study of vorinostat in acute myeloid leukemia', Haematologica, vol. 94, no. 10, pp. 1375-1382. https://doi.org/10.3324/haematol.2009.009217
Schaefer EW, Loaiza-Bonilla A, Juckett M, DiPersio JF, Roy V, Slack JL et al. A phase 2 study of vorinostat in acute myeloid leukemia. Haematologica. 2009 Oct;94(10):1375-1382. https://doi.org/10.3324/haematol.2009.009217
Schaefer, Eric W. ; Loaiza-Bonilla, Arturo ; Juckett, Mark ; DiPersio, John F. ; Roy, Vivek ; Slack, James L ; Wu, Wenting ; Laumann, Kristina ; Espinoza-Delgado, Igor ; Gore, Steven D. / A phase 2 study of vorinostat in acute myeloid leukemia. In: Haematologica. 2009 ; Vol. 94, No. 10. pp. 1375-1382.
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AU - Loaiza-Bonilla, Arturo

AU - Juckett, Mark

AU - DiPersio, John F.

AU - Roy, Vivek

AU - Slack, James L

AU - Wu, Wenting

AU - Laumann, Kristina

AU - Espinoza-Delgado, Igor

AU - Gore, Steven D.

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N2 - Background: This two-stage, multi-institutional, randomized phase 2 trial assessed the toxicity and response rate associated with two treatment schedules of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamic acid; SAHA) in patients with relapsed acute myeloid leukemia and in selected untreated patients with high-risk acute myeloid leukemia. Design and Methods: Patients with relapsed or untreated acute myeloid leukemia who were not candidates for chemotherapy entered one of the two treatment arms. In both arms a total dose of 8400 mg of vorinostat was delivered in each 21-day cycle of treatment: in arm A the dose regimen was 400 mg daily whereas in arm B the dose regimen was 200 mg three times daily for 14 days followed by 1 week rest. Results: Data from all 37 patients were used for the analyses. In arm A (n=15), the confirmed complete remission rate was 0% (95% CI, 0% to 23%); this arm was closed at the planned interim analysis. In arm B (n=22), the confirmed complete remission rate was 4.5% (1 response; 95% CI, 0.4% to 24%), with a duration of response exceeding 398 days. The median time to treatment failure in arm A was 42 days (95% CI, 26 to 57); although a minimum of four cycles of treatment were planned, 11 patients (79%) received no more than two cycles. The median time to treatment failure in arm B was 46 days (95% CI, 20 to 71); 13 patients (59%) received no more than two cycles of treatment. Conclusions: Vorinostat monotherapy demonstrated minimal activity in this group of patients with acute myeloid leukemia. Therapy was discontinued in many patients before the planned four cycles had been administered, either because of failure of vorinostat to control the leukocyte count or patients' and physicians' preference. Future studies of vorinostat in acute myeloid leukemia should focus on combinations with other drugs with which it might interact pharmacodynamically. ClinicalTrials.gov Identifier: NCT00305773.

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