Phase I study of chidamide (CS055/HBI-8000), a new histone deacetylase inhibitor, in patients with advanced solid tumors and lymphomas

Abstract

Chidamide was generally well tolerated in patients with advanced solid tumors or lymphomas in the tested regimens. Favorable PK and PD profiles, as well as encouraging preliminary anti-tumor activity, were demonstrated.

Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

“…In this study, a higher dose of tucidinostat, 40 mg BIW was given, compared to that used in the previous studies. 29 , 36 The most common AE were hematologic abnormalities (thrombocytopenia, neutropenia, leukopenia, anemia, lymphopenia), and gastrointestinal disturbances, which were consistent with previously reported AE with tucidinostat 28 , 29 , 36 as well as with other HDAC inhibitors such as belinostat 11 and romidepsin. 12 In addition, the AE reported in our study were manageable by supportive care and dose modifications.…”

Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

“…In this study, a higher dose of tucidinostat, 40 mg BIW was given, compared to that used in the previous studies. 29 , 36 The most common AE were hematologic abnormalities (thrombocytopenia, neutropenia, leukopenia, anemia, lymphopenia), and gastrointestinal disturbances, which were consistent with previously reported AE with tucidinostat 28 , 29 , 36 as well as with other HDAC inhibitors such as belinostat 11 and romidepsin. 12 In addition, the AE reported in our study were manageable by supportive care and dose modifications.…”

Development and validation of a sensitive HPLC–MS/MS method for determination of chidamide (epidaza), a new benzamide class of selective histone deacetylase inhibitor, in human plasma and its clinical application

“…Measurable chidamide concentrations ranged from 1.3 to 92.8 ng/mL, with the AUClast and t 1/2 were 719.5 ± 144.2 ng h/mL and 16.6 ± 1.2 h, respectively. When referred to a previously published phase I study in patients receiving a similar dose of 32.5 mg chidamide whose pharmacokinetic data were also analyzed by this method, the obtained AUClast and t 1/2 were 875 ± 512 ng h/mL and 17.5 ± 4.2 h, respectively [26], which was very consistent with the current data described in this paper and thus further confirming the reproducibility and accuracy of the method during its clinical application.…”

Safety of chidamide plus rituximab in elderly patients with relapsed or refractory B-cell lymphoma in China: a multicenter, single-arm, phase II study

“…The main AEs were myelosuppression, fatigue, and hyperuricemia. The most common grade 3/4 adverse event was myelosuppression (≤15.4%), which is similar to, or lower than, other previously reported HDACiassociated regimens (9,20,21,31). The myelosuppression was of short duration and resolved using G-CSF without translating into excessive infections.…”

Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

“…In this study, a higher dose of tucidinostat, 40 mg BIW was given, compared to that used in the previous studies. 29 , 36 The most common AE were hematologic abnormalities (thrombocytopenia, neutropenia, leukopenia, anemia, lymphopenia), and gastrointestinal disturbances, which were consistent with previously reported AE with tucidinostat 28 , 29 , 36 as well as with other HDAC inhibitors such as belinostat 11 and romidepsin. 12 In addition, the AE reported in our study were manageable by supportive care and dose modifications.…”

Development and validation of a sensitive HPLC–MS/MS method for determination of chidamide (epidaza), a new benzamide class of selective histone deacetylase inhibitor, in human plasma and its clinical application

“…Measurable chidamide concentrations ranged from 1.3 to 92.8 ng/mL, with the AUClast and t 1/2 were 719.5 ± 144.2 ng h/mL and 16.6 ± 1.2 h, respectively. When referred to a previously published phase I study in patients receiving a similar dose of 32.5 mg chidamide whose pharmacokinetic data were also analyzed by this method, the obtained AUClast and t 1/2 were 875 ± 512 ng h/mL and 17.5 ± 4.2 h, respectively [26], which was very consistent with the current data described in this paper and thus further confirming the reproducibility and accuracy of the method during its clinical application.…”

Safety of chidamide plus rituximab in elderly patients with relapsed or refractory B-cell lymphoma in China: a multicenter, single-arm, phase II study

“…The main AEs were myelosuppression, fatigue, and hyperuricemia. The most common grade 3/4 adverse event was myelosuppression (≤15.4%), which is similar to, or lower than, other previously reported HDACiassociated regimens (9,20,21,31). The myelosuppression was of short duration and resolved using G-CSF without translating into excessive infections.…”

Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

“…In this study, a higher dose of tucidinostat, 40 mg BIW was given, compared to that used in the previous studies. 29 , 36 The most common AE were hematologic abnormalities (thrombocytopenia, neutropenia, leukopenia, anemia, lymphopenia), and gastrointestinal disturbances, which were consistent with previously reported AE with tucidinostat 28 , 29 , 36 as well as with other HDAC inhibitors such as belinostat 11 and romidepsin. 12 In addition, the AE reported in our study were manageable by supportive care and dose modifications.…”

Development and validation of a sensitive HPLC–MS/MS method for determination of chidamide (epidaza), a new benzamide class of selective histone deacetylase inhibitor, in human plasma and its clinical application

“…Measurable chidamide concentrations ranged from 1.3 to 92.8 ng/mL, with the AUClast and t 1/2 were 719.5 ± 144.2 ng h/mL and 16.6 ± 1.2 h, respectively. When referred to a previously published phase I study in patients receiving a similar dose of 32.5 mg chidamide whose pharmacokinetic data were also analyzed by this method, the obtained AUClast and t 1/2 were 875 ± 512 ng h/mL and 17.5 ± 4.2 h, respectively [26], which was very consistent with the current data described in this paper and thus further confirming the reproducibility and accuracy of the method during its clinical application.…”

Safety of chidamide plus rituximab in elderly patients with relapsed or refractory B-cell lymphoma in China: a multicenter, single-arm, phase II study

“…The main AEs were myelosuppression, fatigue, and hyperuricemia. The most common grade 3/4 adverse event was myelosuppression (≤15.4%), which is similar to, or lower than, other previously reported HDACiassociated regimens (9,20,21,31). The myelosuppression was of short duration and resolved using G-CSF without translating into excessive infections.…”