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

doi:10.1080/10428194.2016.1276287

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

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1349-1357
Number of pages	9
Journal	Leukemia and Lymphoma
Volume	58
Issue number	6
DOIs	https://doi.org/10.1080/10428194.2016.1276287
State	Published - Jun 3 2017

Funding

The authors thank Elizabeth Stoddert Collins, MA, CCRP for assistance with data acquisition. This work was supported by the National Institute of Health [NCI R01 CA205607; NCI R01 CA167708; P50 CA 142509; NCI R21 CA137823; NCI P30 CA016059; NCRR M01 RR00065] and the Leukemia and Lymphoma Society [6472-15].

Keywords

Bortezomib
lymphoma
phase 1 clinical trial
romidepsin

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/10428194.2016.1276287

Cite this

Holkova, B., Yazbeck, V., Kmieciak, M., Bose, P., Ma, S., Kimball, A., Tombes, M. B., Shrader, E., Wan, W., Weir-Wiggins, C., Singh, A., Hogan, K. T., Conine, S., Sankala, H., Roberts, J. D., Shea, T. C., & 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, 58(6), 1349-1357. https://doi.org/10.1080/10428194.2016.1276287

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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.",

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

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doi = "10.1080/10428194.2016.1276287",

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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. https://doi.org/10.1080/10428194.2016.1276287

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

Research output: Contribution to journal › Article › peer-review

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AU - Holkova, Beata

AU - Yazbeck, Victor

AU - Kmieciak, Maciej

AU - Bose, Prithviraj

AU - Ma, Shuo

AU - Kimball, Amy

AU - Tombes, Mary Beth

AU - Shrader, Ellen

AU - Wan, Wen

AU - Weir-Wiggins, Caryn

AU - Singh, Amanda

AU - Hogan, Kevin T.

AU - Conine, Sarah

AU - Sankala, Heidi

AU - Roberts, John D.

AU - Shea, Thomas C.

AU - Grant, Steven

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N2 - 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.

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KW - lymphoma

KW - phase 1 clinical trial

KW - romidepsin

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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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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