Mocetinostat for relapsed classical Hodgkin's lymphoma: An open-label, single-arm, phase 2 trial

Anas Younes, Yasuhiro Oki, Robert G Bociek, John Kuruvilla, Michelle Fanale, Sattva Neelapu, Amanda Copeland, Daniela Buglio, Ahmed Galal, Jeffrey Besterman, Zuomei Li, Michel Drouin, Tracy Patterson, M. Renee Ward, Jessica K. Paulus, Yuan Ji, L. Jeffrey Medeiros, Robert E. Martell

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Background: The prognosis of patients with relapsed Hodgkin's lymphoma, especially those who relapse after stem-cell transplantation, is poor, and the development of new agents for this patient population is an unmet medical need. We tested the safety and efficacy of mocetinostat, an oral isotype-selective histone deacetylase inhibitor, in patients with relapsed classical Hodgkin's lymphoma. Methods: Patients with relapsed or refractory classical Hodgkin's lymphoma aged 18 years or older were treated with mocetinostat administered orally three times per week, in 28-day cycles. Two doses were assessed (85 mg and 110 mg). Patients were treated until disease progression or prohibitive toxicity. The primary outcome was disease control rate, defined as complete response, partial response, or stable disease (for at least six cycles), analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00358982. Findings: 51 patients were enrolled. Initially, 23 patients were enrolled in the 110 mg cohort. Subsequently, because toxicity-related dose reductions were necessary in the 110 mg cohort, we treated 28 additional patients with a dose of 85 mg. On the basis of intent-to-treat analysis, the disease control rate was 35% (eight of 23 patients) in the 110 mg group and 25% (seven of 28) in the 85 mg group. 12 patients (24%) discontinued treatment because of adverse events, nine (32%) in the 85 mg cohort and three (13%) in the 110 mg cohort. The most frequent treatment-related grade 3 and 4 adverse events were neutropenia (four patients [17%] in the 110 mg group, three [11%] in the 85 mg group); fatigue (five patients [22%] in the 110 mg group, three [11%] in the 85 mg group); and pneumonia (four patients [17%] in the 110 mg group, two [7%] in the 85 mg group). Four patients, all in the 110 mg cohort, died during the study, of which two might have been related to treatment. Interpretation: Mocetinostat, 85 mg three times per week, has promising single-agent clinical activity with manageable toxicity in patients with relapsed classical Hodgkin's lymphoma. Funding: MethylGene Inc, Montreal, Canada; Celgene Corporation, Summit, NJ, USA; Tufts Medical Center, Boston, MA, USA.

Original languageEnglish (US)
Pages (from-to)1222-1228
Number of pages7
JournalThe Lancet Oncology
Volume12
Issue number13
DOIs
StatePublished - Dec 1 2011

Fingerprint

Hodgkin Disease
mocetinostat
Histone Deacetylase Inhibitors
Stem Cell Transplantation
Proxy
Neutropenia
Canada
Fatigue
Disease Progression
Pneumonia
Therapeutics

ASJC Scopus subject areas

  • Oncology

Cite this

Mocetinostat for relapsed classical Hodgkin's lymphoma : An open-label, single-arm, phase 2 trial. / Younes, Anas; Oki, Yasuhiro; Bociek, Robert G; Kuruvilla, John; Fanale, Michelle; Neelapu, Sattva; Copeland, Amanda; Buglio, Daniela; Galal, Ahmed; Besterman, Jeffrey; Li, Zuomei; Drouin, Michel; Patterson, Tracy; Ward, M. Renee; Paulus, Jessica K.; Ji, Yuan; Medeiros, L. Jeffrey; Martell, Robert E.

In: The Lancet Oncology, Vol. 12, No. 13, 01.12.2011, p. 1222-1228.

Research output: Contribution to journalArticle

Younes, A, Oki, Y, Bociek, RG, Kuruvilla, J, Fanale, M, Neelapu, S, Copeland, A, Buglio, D, Galal, A, Besterman, J, Li, Z, Drouin, M, Patterson, T, Ward, MR, Paulus, JK, Ji, Y, Medeiros, LJ & Martell, RE 2011, 'Mocetinostat for relapsed classical Hodgkin's lymphoma: An open-label, single-arm, phase 2 trial', The Lancet Oncology, vol. 12, no. 13, pp. 1222-1228. https://doi.org/10.1016/S1470-2045(11)70265-0
Younes, Anas ; Oki, Yasuhiro ; Bociek, Robert G ; Kuruvilla, John ; Fanale, Michelle ; Neelapu, Sattva ; Copeland, Amanda ; Buglio, Daniela ; Galal, Ahmed ; Besterman, Jeffrey ; Li, Zuomei ; Drouin, Michel ; Patterson, Tracy ; Ward, M. Renee ; Paulus, Jessica K. ; Ji, Yuan ; Medeiros, L. Jeffrey ; Martell, Robert E. / Mocetinostat for relapsed classical Hodgkin's lymphoma : An open-label, single-arm, phase 2 trial. In: The Lancet Oncology. 2011 ; Vol. 12, No. 13. pp. 1222-1228.
@article{45bfbae013304788b3aea80c8d890d77,
title = "Mocetinostat for relapsed classical Hodgkin's lymphoma: An open-label, single-arm, phase 2 trial",
abstract = "Background: The prognosis of patients with relapsed Hodgkin's lymphoma, especially those who relapse after stem-cell transplantation, is poor, and the development of new agents for this patient population is an unmet medical need. We tested the safety and efficacy of mocetinostat, an oral isotype-selective histone deacetylase inhibitor, in patients with relapsed classical Hodgkin's lymphoma. Methods: Patients with relapsed or refractory classical Hodgkin's lymphoma aged 18 years or older were treated with mocetinostat administered orally three times per week, in 28-day cycles. Two doses were assessed (85 mg and 110 mg). Patients were treated until disease progression or prohibitive toxicity. The primary outcome was disease control rate, defined as complete response, partial response, or stable disease (for at least six cycles), analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00358982. Findings: 51 patients were enrolled. Initially, 23 patients were enrolled in the 110 mg cohort. Subsequently, because toxicity-related dose reductions were necessary in the 110 mg cohort, we treated 28 additional patients with a dose of 85 mg. On the basis of intent-to-treat analysis, the disease control rate was 35{\%} (eight of 23 patients) in the 110 mg group and 25{\%} (seven of 28) in the 85 mg group. 12 patients (24{\%}) discontinued treatment because of adverse events, nine (32{\%}) in the 85 mg cohort and three (13{\%}) in the 110 mg cohort. The most frequent treatment-related grade 3 and 4 adverse events were neutropenia (four patients [17{\%}] in the 110 mg group, three [11{\%}] in the 85 mg group); fatigue (five patients [22{\%}] in the 110 mg group, three [11{\%}] in the 85 mg group); and pneumonia (four patients [17{\%}] in the 110 mg group, two [7{\%}] in the 85 mg group). Four patients, all in the 110 mg cohort, died during the study, of which two might have been related to treatment. Interpretation: Mocetinostat, 85 mg three times per week, has promising single-agent clinical activity with manageable toxicity in patients with relapsed classical Hodgkin's lymphoma. Funding: MethylGene Inc, Montreal, Canada; Celgene Corporation, Summit, NJ, USA; Tufts Medical Center, Boston, MA, USA.",
author = "Anas Younes and Yasuhiro Oki and Bociek, {Robert G} and John Kuruvilla and Michelle Fanale and Sattva Neelapu and Amanda Copeland and Daniela Buglio and Ahmed Galal and Jeffrey Besterman and Zuomei Li and Michel Drouin and Tracy Patterson and Ward, {M. Renee} and Paulus, {Jessica K.} and Yuan Ji and Medeiros, {L. Jeffrey} and Martell, {Robert E.}",
year = "2011",
month = "12",
day = "1",
doi = "10.1016/S1470-2045(11)70265-0",
language = "English (US)",
volume = "12",
pages = "1222--1228",
journal = "The Lancet Oncology",
issn = "1470-2045",
publisher = "Lancet Publishing Group",
number = "13",

}

TY - JOUR

T1 - Mocetinostat for relapsed classical Hodgkin's lymphoma

T2 - An open-label, single-arm, phase 2 trial

AU - Younes, Anas

AU - Oki, Yasuhiro

AU - Bociek, Robert G

AU - Kuruvilla, John

AU - Fanale, Michelle

AU - Neelapu, Sattva

AU - Copeland, Amanda

AU - Buglio, Daniela

AU - Galal, Ahmed

AU - Besterman, Jeffrey

AU - Li, Zuomei

AU - Drouin, Michel

AU - Patterson, Tracy

AU - Ward, M. Renee

AU - Paulus, Jessica K.

AU - Ji, Yuan

AU - Medeiros, L. Jeffrey

AU - Martell, Robert E.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Background: The prognosis of patients with relapsed Hodgkin's lymphoma, especially those who relapse after stem-cell transplantation, is poor, and the development of new agents for this patient population is an unmet medical need. We tested the safety and efficacy of mocetinostat, an oral isotype-selective histone deacetylase inhibitor, in patients with relapsed classical Hodgkin's lymphoma. Methods: Patients with relapsed or refractory classical Hodgkin's lymphoma aged 18 years or older were treated with mocetinostat administered orally three times per week, in 28-day cycles. Two doses were assessed (85 mg and 110 mg). Patients were treated until disease progression or prohibitive toxicity. The primary outcome was disease control rate, defined as complete response, partial response, or stable disease (for at least six cycles), analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00358982. Findings: 51 patients were enrolled. Initially, 23 patients were enrolled in the 110 mg cohort. Subsequently, because toxicity-related dose reductions were necessary in the 110 mg cohort, we treated 28 additional patients with a dose of 85 mg. On the basis of intent-to-treat analysis, the disease control rate was 35% (eight of 23 patients) in the 110 mg group and 25% (seven of 28) in the 85 mg group. 12 patients (24%) discontinued treatment because of adverse events, nine (32%) in the 85 mg cohort and three (13%) in the 110 mg cohort. The most frequent treatment-related grade 3 and 4 adverse events were neutropenia (four patients [17%] in the 110 mg group, three [11%] in the 85 mg group); fatigue (five patients [22%] in the 110 mg group, three [11%] in the 85 mg group); and pneumonia (four patients [17%] in the 110 mg group, two [7%] in the 85 mg group). Four patients, all in the 110 mg cohort, died during the study, of which two might have been related to treatment. Interpretation: Mocetinostat, 85 mg three times per week, has promising single-agent clinical activity with manageable toxicity in patients with relapsed classical Hodgkin's lymphoma. Funding: MethylGene Inc, Montreal, Canada; Celgene Corporation, Summit, NJ, USA; Tufts Medical Center, Boston, MA, USA.

AB - Background: The prognosis of patients with relapsed Hodgkin's lymphoma, especially those who relapse after stem-cell transplantation, is poor, and the development of new agents for this patient population is an unmet medical need. We tested the safety and efficacy of mocetinostat, an oral isotype-selective histone deacetylase inhibitor, in patients with relapsed classical Hodgkin's lymphoma. Methods: Patients with relapsed or refractory classical Hodgkin's lymphoma aged 18 years or older were treated with mocetinostat administered orally three times per week, in 28-day cycles. Two doses were assessed (85 mg and 110 mg). Patients were treated until disease progression or prohibitive toxicity. The primary outcome was disease control rate, defined as complete response, partial response, or stable disease (for at least six cycles), analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00358982. Findings: 51 patients were enrolled. Initially, 23 patients were enrolled in the 110 mg cohort. Subsequently, because toxicity-related dose reductions were necessary in the 110 mg cohort, we treated 28 additional patients with a dose of 85 mg. On the basis of intent-to-treat analysis, the disease control rate was 35% (eight of 23 patients) in the 110 mg group and 25% (seven of 28) in the 85 mg group. 12 patients (24%) discontinued treatment because of adverse events, nine (32%) in the 85 mg cohort and three (13%) in the 110 mg cohort. The most frequent treatment-related grade 3 and 4 adverse events were neutropenia (four patients [17%] in the 110 mg group, three [11%] in the 85 mg group); fatigue (five patients [22%] in the 110 mg group, three [11%] in the 85 mg group); and pneumonia (four patients [17%] in the 110 mg group, two [7%] in the 85 mg group). Four patients, all in the 110 mg cohort, died during the study, of which two might have been related to treatment. Interpretation: Mocetinostat, 85 mg three times per week, has promising single-agent clinical activity with manageable toxicity in patients with relapsed classical Hodgkin's lymphoma. Funding: MethylGene Inc, Montreal, Canada; Celgene Corporation, Summit, NJ, USA; Tufts Medical Center, Boston, MA, USA.

UR - http://www.scopus.com/inward/record.url?scp=82555187781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82555187781&partnerID=8YFLogxK

U2 - 10.1016/S1470-2045(11)70265-0

DO - 10.1016/S1470-2045(11)70265-0

M3 - Article

C2 - 22033282

AN - SCOPUS:82555187781

VL - 12

SP - 1222

EP - 1228

JO - The Lancet Oncology

JF - The Lancet Oncology

SN - 1470-2045

IS - 13

ER -