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A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma
- Source :
- Clinical Cancer Research. 22:1059-1066
- Publication Year :
- 2016
- Publisher :
- American Association for Cancer Research (AACR), 2016.
-
Abstract
- Purpose: Additional targeted therapeutics are needed for the treatment of lymphoma. Abexinostat is an oral pan-histone deacetylase inhibitor (HDACi) displaying potent activity in preclinical models. We conducted a multicenter phase I/II study (N = 55) with single-agent abexinostat in relapsed/refractory lymphoma. Experimental Design: In phase I, 25 heavily pretreated patients with any lymphoma subtype received oral abexinostat ranging from 30 to 60 mg/m2 twice daily 5 days/week for 3 weeks or 7 days/week given every other week. Phase II evaluated abexinostat at the maximum tolerated dose in 30 patients with relapsed/refractory follicular lymphoma or mantle cell lymphoma. Results: The recommended phase II dose was 45 mg/m2 twice daily (90 mg/m2 total), 7 days/week given every other week. Of the 30 follicular lymphoma and mantle cell lymphoma patients enrolled in phase II, 25 (14 follicular lymphoma, 11 mantle cell lymphoma) were response-evaluable. Tumor size was reduced in 86% of follicular lymphoma patients with an investigator-assessed ORR of 64.3% for evaluable patients [intent-to-treat (ITT) ORR 56.3%]. Median duration of response was not reached, and median progression-free survival (PFS) was 20.5 months (1.2–22.3+). Of responding follicular lymphoma patients, 89% were on study/drug >8 months. In mantle cell lymphoma, the ORR was 27.3% for evaluable patients (ITT ORR 21.4%), and median PFS was 3.9 months (range, 0.1–11.5). Grade 3–4 treatment-related adverse events (phase II) with ≥10% incidence were thrombocytopenia (20%), fatigue (16.7%), and neutropenia (13.3%) with rare QTc prolongation and no deaths. Conclusions: The pan-HDACi, abexinostat, was overall well tolerated and had significant clinical activity in follicular lymphoma, including highly durable responses in this multiply relapsed patient population. Clin Cancer Res; 22(5); 1059–66. ©2015 AACR.
- Subjects :
- Adult
Male
0301 basic medicine
Cancer Research
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions
Maximum Tolerated Dose
Population
Abexinostat
Lymphoma, Mantle-Cell
Neutropenia
Hydroxamic Acids
Gastroenterology
Disease-Free Survival
Drug Administration Schedule
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Recurrence
Internal medicine
medicine
Humans
Adverse effect
education
Lymphoma, Follicular
Aged
Benzofurans
Aged, 80 and over
education.field_of_study
business.industry
Incidence (epidemiology)
Middle Aged
medicine.disease
Lymphoma
Surgery
Histone Deacetylase Inhibitors
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Female
Mantle cell lymphoma
Neoplasm Recurrence, Local
Refractory Follicular Lymphoma
business
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....2bcfc109ef12535f318cd52765bdbceb