Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma

Richard L. Piekarz, Robin Frye, Maria Turner, John J. Wright, Steven L. Allen, Mark H. Kirschbaum, Jasmine Zain, H. Miles Prince, John P. Leonard, Larisa J. Geskin, Craig Reeder, David Joske, William D. Figg, Erin R. Gardner, Seth M. Steinberg, Elaine S. Jaffe, Maryalice Stetler-Stevenson, Stephen Lade, A. Tito Fojo, Susan E. Bates

Research output: Contribution to journalArticle

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Abstract

Purpose: Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods: The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results: Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion: The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.

Original languageEnglish (US)
Pages (from-to)5410-5417
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number32
DOIs
StatePublished - Nov 10 2009
Externally publishedYes

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Cutaneous T-Cell Lymphoma
Histone Deacetylase Inhibitors
T-Cell Lymphoma
romidepsin
Depsipeptides
Mycosis Fungoides
Agranulocytosis
Thrombocytopenia
Antineoplastic Agents
Nausea
Vomiting
Fatigue
Pharmacokinetics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. / Piekarz, Richard L.; Frye, Robin; Turner, Maria; Wright, John J.; Allen, Steven L.; Kirschbaum, Mark H.; Zain, Jasmine; Prince, H. Miles; Leonard, John P.; Geskin, Larisa J.; Reeder, Craig; Joske, David; Figg, William D.; Gardner, Erin R.; Steinberg, Seth M.; Jaffe, Elaine S.; Stetler-Stevenson, Maryalice; Lade, Stephen; Fojo, A. Tito; Bates, Susan E.

In: Journal of Clinical Oncology, Vol. 27, No. 32, 10.11.2009, p. 5410-5417.

Research output: Contribution to journalArticle

Piekarz, RL, Frye, R, Turner, M, Wright, JJ, Allen, SL, Kirschbaum, MH, Zain, J, Prince, HM, Leonard, JP, Geskin, LJ, Reeder, C, Joske, D, Figg, WD, Gardner, ER, Steinberg, SM, Jaffe, ES, Stetler-Stevenson, M, Lade, S, Fojo, AT & Bates, SE 2009, 'Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma', Journal of Clinical Oncology, vol. 27, no. 32, pp. 5410-5417. https://doi.org/10.1200/JCO.2008.21.6150
Piekarz, Richard L. ; Frye, Robin ; Turner, Maria ; Wright, John J. ; Allen, Steven L. ; Kirschbaum, Mark H. ; Zain, Jasmine ; Prince, H. Miles ; Leonard, John P. ; Geskin, Larisa J. ; Reeder, Craig ; Joske, David ; Figg, William D. ; Gardner, Erin R. ; Steinberg, Seth M. ; Jaffe, Elaine S. ; Stetler-Stevenson, Maryalice ; Lade, Stephen ; Fojo, A. Tito ; Bates, Susan E. / Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 32. pp. 5410-5417.
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abstract = "Purpose: Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods: The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or S{\'e}zary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results: Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87{\%}) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34{\%} (95{\%} CI, 23{\%} to 46{\%}). The median duration of response was 13.7 months. Conclusion: The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.",
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T1 - Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma

AU - Piekarz, Richard L.

AU - Frye, Robin

AU - Turner, Maria

AU - Wright, John J.

AU - Allen, Steven L.

AU - Kirschbaum, Mark H.

AU - Zain, Jasmine

AU - Prince, H. Miles

AU - Leonard, John P.

AU - Geskin, Larisa J.

AU - Reeder, Craig

AU - Joske, David

AU - Figg, William D.

AU - Gardner, Erin R.

AU - Steinberg, Seth M.

AU - Jaffe, Elaine S.

AU - Stetler-Stevenson, Maryalice

AU - Lade, Stephen

AU - Fojo, A. Tito

AU - Bates, Susan E.

PY - 2009/11/10

Y1 - 2009/11/10

N2 - Purpose: Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods: The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results: Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion: The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.

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