A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma

Beata Holkova, Victor Yazbeck, Maciej Kmieciak, Prithviraj Bose, Shuo Ma, Amy Kimball, Mary Beth Tombes, Ellen Shrader, Wen Wan, Caryn Weir-Wiggins, Amanda Singh, Kevin T. Hogan, Sarah Conine, Heidi Sankala, John D. Roberts, Thomas C. Shea, Steven Grant

Research output: Contribution to journalArticle

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Abstract

A phase 1 study was conducted to determine the dose-limiting toxicities and maximum-tolerated dose (MTD) for bortezomib followed by romidepsin on days 1, 8, and 15 in patients with relapsed/refractory CLL/SLL or B- or T-cell lymphoma. Eighteen treated patients were evaluable for response. The MTD was 1.3 mg/m2 bortezomib and 10 mg/m2 romidepsin; median treatment duration was 3 cycles at this dose. The dose-limiting toxicities were grade 3 fatigue, vomiting, and chills. Two patients had partial responses, one lasting >2 years, 8 had stable disease, and 8 had progressive disease. The median duration of stable disease was 3.5 cycles. Correlative studies examining expression of NF-кB, XIAP, Bcl-xL, and Bim yielded variable results. The safety profile was consistent with that reported for single-agent bortezomib and romidepsin. This regimen has modest activity in heavily pretreated patients with relapsed/refractory CLL or B- or T-cell lymphoma. NCT00963274.

LanguageEnglish (US)
Pages1349-1357
Number of pages9
JournalLeukemia and Lymphoma
Volume58
Issue number6
DOIs
StatePublished - Jun 3 2017

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Peripheral T-Cell Lymphoma
Cutaneous T-Cell Lymphoma
B-Cell Lymphoma
B-Cell Chronic Lymphocytic Leukemia
Maximum Tolerated Dose
T-Cell Lymphoma
Chills
Vomiting
Fatigue
Safety
Bortezomib
romidepsin

Keywords

  • Bortezomib
  • lymphoma
  • phase 1 clinical trial
  • romidepsin

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma. / Holkova, Beata; Yazbeck, Victor; Kmieciak, Maciej; Bose, Prithviraj; Ma, Shuo; Kimball, Amy; Tombes, Mary Beth; Shrader, Ellen; Wan, Wen; Weir-Wiggins, Caryn; Singh, Amanda; Hogan, Kevin T.; Conine, Sarah; Sankala, Heidi; Roberts, John D.; Shea, Thomas C.; Grant, Steven.

In: Leukemia and Lymphoma, Vol. 58, No. 6, 03.06.2017, p. 1349-1357.

Research output: Contribution to journalArticle

Holkova, B, Yazbeck, V, Kmieciak, M, Bose, P, Ma, S, Kimball, A, Tombes, MB, Shrader, E, Wan, W, Weir-Wiggins, C, Singh, A, Hogan, KT, Conine, S, Sankala, H, Roberts, JD, Shea, TC & Grant, S 2017, 'A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma' Leukemia and Lymphoma, vol. 58, no. 6, pp. 1349-1357. DOI: 10.1080/10428194.2016.1276287
Holkova, Beata ; Yazbeck, Victor ; Kmieciak, Maciej ; Bose, Prithviraj ; Ma, Shuo ; Kimball, Amy ; Tombes, Mary Beth ; Shrader, Ellen ; Wan, Wen ; Weir-Wiggins, Caryn ; Singh, Amanda ; Hogan, Kevin T. ; Conine, Sarah ; Sankala, Heidi ; Roberts, John D. ; Shea, Thomas C. ; Grant, Steven. / A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma. In: Leukemia and Lymphoma. 2017 ; Vol. 58, No. 6. pp. 1349-1357
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