Originally published as JCO Early Release 10.1200/JCO.2008.21.6150 on October 13 2009

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Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma

From the Center for Cancer Research and Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda; Clinical Pharmacology Program, SAIC-Frederick, Frederick, MD; North Shore University Hospital, Manhasset; New York Presbyterian Hospital, New York, NY; City of Hope National Cancer Center, Duarte, CA; University of Pittsburgh, Pittsburgh, PA; Mayo Clinic Scottsdale, Scottsdale, AZ; Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Victoria; and Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

Corresponding author: Richard L. Piekarz, MD, PhD, 10 Center Dr, MSC 1903, Bldg 10, Rm 12N226, Bethesda, MD 20892-1903; e-mail: rpiekarz{at}nih.gov.

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.

See accompanying article on page 5459

Supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research and by a Cooperative Research and Development Agreement with Gloucester Pharmaceuticals, Cambridge, MA; also supported in part by federal funds from the National Cancer Institute, NIH, under Grant No. N01-CO-12400 (E.R.G.).

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services; mention of trade names, commercial products, or organizations does not imply endorsement by the US Government.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00020436 [ClinicalTrials.gov] .

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