Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma

Stephen E. Spurgeon, Kamal Sharma, David Claxton, W. Christopher Ehmann, Jeffrey Pu, Sara Shimko, August Stewart, Nan Subbiah, Gundula Palmbach, Francis LeBlanc, Emile Latour, Yi Yi Chen, Motomi Mori, Zainul Hasanali, Elliot M. Epner

Research output: Contribution to journalArticle

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Abstract

Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non-Hodgkin lymphomas (NHL) in this phase 1–2 study (NCT00764517). Treatment included cladribine 5 mg/m2 intravenously (IV) (days 1–5), rituximab 375 mg/m2 IV (weekly 4× for cycle 1 and 1×/month) and vorinostat orally once daily (days 1–14) every 28 days for up to six cycles. Phase 1 included relapsed patients (n = 10) in a standard 3 + 3 dose escalation design (vorinostat: 200, 300 and 400 mg). No dose-limiting toxicities were seen. The phase 2 dose for vorinostat was 400 mg po (days 1–14). The majority of phase 2 patients had mantle cell lymphoma (MCL) (n = 57; 39 previously untreated, 10 relapsed). The primary objective was objective response rate [complete response (CR) + partial response] which was 39% (7/18) in relapsed patients and 97% (38/39) with 80% (31/39) attaining a CR in previously untreated MCL. At a median follow-up of 42 months, median progression-free survival (PFS) and overall survival (OS) for relapsed NHL were 19·5 [95% confidence interval (CI): 2·0–33·0] and 25·0 (95% CI: 12·0–45·0) months respectively. Median PFS for previously untreated MCL was 84·0 months; OS could not be estimated. Toxicities were primarily haematological.

Original languageEnglish (US)
Pages (from-to)845-854
Number of pages10
JournalBritish Journal of Haematology
Volume186
Issue number6
DOIs
StatePublished - Sep 1 2019

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Cladribine
Mantle-Cell Lymphoma
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Disease-Free Survival
Confidence Intervals
Survival
DNA Methylation
Acetylation
Histones
Lymphoma
vorinostat
Rituximab

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Spurgeon, Stephen E. ; Sharma, Kamal ; Claxton, David ; Ehmann, W. Christopher ; Pu, Jeffrey ; Shimko, Sara ; Stewart, August ; Subbiah, Nan ; Palmbach, Gundula ; LeBlanc, Francis ; Latour, Emile ; Chen, Yi Yi ; Mori, Motomi ; Hasanali, Zainul ; Epner, Elliot M. / Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma. In: British Journal of Haematology. 2019 ; Vol. 186, No. 6. pp. 845-854.
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title = "Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma",
abstract = "Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non-Hodgkin lymphomas (NHL) in this phase 1–2 study (NCT00764517). Treatment included cladribine 5 mg/m2 intravenously (IV) (days 1–5), rituximab 375 mg/m2 IV (weekly 4× for cycle 1 and 1×/month) and vorinostat orally once daily (days 1–14) every 28 days for up to six cycles. Phase 1 included relapsed patients (n = 10) in a standard 3 + 3 dose escalation design (vorinostat: 200, 300 and 400 mg). No dose-limiting toxicities were seen. The phase 2 dose for vorinostat was 400 mg po (days 1–14). The majority of phase 2 patients had mantle cell lymphoma (MCL) (n = 57; 39 previously untreated, 10 relapsed). The primary objective was objective response rate [complete response (CR) + partial response] which was 39{\%} (7/18) in relapsed patients and 97{\%} (38/39) with 80{\%} (31/39) attaining a CR in previously untreated MCL. At a median follow-up of 42 months, median progression-free survival (PFS) and overall survival (OS) for relapsed NHL were 19·5 [95{\%} confidence interval (CI): 2·0–33·0] and 25·0 (95{\%} CI: 12·0–45·0) months respectively. Median PFS for previously untreated MCL was 84·0 months; OS could not be estimated. Toxicities were primarily haematological.",
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Spurgeon, SE, Sharma, K, Claxton, D, Ehmann, WC, Pu, J, Shimko, S, Stewart, A, Subbiah, N, Palmbach, G, LeBlanc, F, Latour, E, Chen, YY, Mori, M, Hasanali, Z & Epner, EM 2019, 'Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma', British Journal of Haematology, vol. 186, no. 6, pp. 845-854. https://doi.org/10.1111/bjh.16008

Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma. / Spurgeon, Stephen E.; Sharma, Kamal; Claxton, David; Ehmann, W. Christopher; Pu, Jeffrey; Shimko, Sara; Stewart, August; Subbiah, Nan; Palmbach, Gundula; LeBlanc, Francis; Latour, Emile; Chen, Yi Yi; Mori, Motomi; Hasanali, Zainul; Epner, Elliot M.

In: British Journal of Haematology, Vol. 186, No. 6, 01.09.2019, p. 845-854.

Research output: Contribution to journalArticle

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T1 - Phase 1–2 study of vorinostat (SAHA), cladribine and rituximab (SCR) in relapsed B-cell non-Hodgkin lymphoma and previously untreated mantle cell lymphoma

AU - Spurgeon, Stephen E.

AU - Sharma, Kamal

AU - Claxton, David

AU - Ehmann, W. Christopher

AU - Pu, Jeffrey

AU - Shimko, Sara

AU - Stewart, August

AU - Subbiah, Nan

AU - Palmbach, Gundula

AU - LeBlanc, Francis

AU - Latour, Emile

AU - Chen, Yi Yi

AU - Mori, Motomi

AU - Hasanali, Zainul

AU - Epner, Elliot M.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Altered DNA methylation and histone acetylation in lymphoma provided the rationale for using vorinostat (SAHA), cladribine and rituximab (SCR) in non-Hodgkin lymphomas (NHL) in this phase 1–2 study (NCT00764517). Treatment included cladribine 5 mg/m2 intravenously (IV) (days 1–5), rituximab 375 mg/m2 IV (weekly 4× for cycle 1 and 1×/month) and vorinostat orally once daily (days 1–14) every 28 days for up to six cycles. Phase 1 included relapsed patients (n = 10) in a standard 3 + 3 dose escalation design (vorinostat: 200, 300 and 400 mg). No dose-limiting toxicities were seen. The phase 2 dose for vorinostat was 400 mg po (days 1–14). The majority of phase 2 patients had mantle cell lymphoma (MCL) (n = 57; 39 previously untreated, 10 relapsed). The primary objective was objective response rate [complete response (CR) + partial response] which was 39% (7/18) in relapsed patients and 97% (38/39) with 80% (31/39) attaining a CR in previously untreated MCL. At a median follow-up of 42 months, median progression-free survival (PFS) and overall survival (OS) for relapsed NHL were 19·5 [95% confidence interval (CI): 2·0–33·0] and 25·0 (95% CI: 12·0–45·0) months respectively. Median PFS for previously untreated MCL was 84·0 months; OS could not be estimated. Toxicities were primarily haematological.

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