A clinical trial of the investigational drug abexinostat in patients with non-Hodgkin’s lymphoma or chronic lymphocytic leukemia demonstrated that the treatment may be suitable for these types of cancer, but more studies are needed to improve dosing schedules.
Abexinostat is a new type of histone deacetylase (HDAC) inhibitor — a drug class that has been used successfully in cancers originating in T-cells. The trial was an attempt to explore the possibility of also treating B-cell related tumors with this type of drug.
The study, “Safety And Efficacy Of Abexinostat, A Pan-Histone Deacetylase Inhibitor, In Non-Hodgkin Lymphoma And Chronic Lymphocytic Leukemia: Results Of A Phase 2 Study,” was headed by researchers at the Gustave Roussy Cancer Institute in France. The report was published in the journal Haematologica.
The Phase 2 clinical trial, registered in the European clinical trials registry (EudraCT-2009-013691-47), enrolled 100 patients with relapsed/refractory non-Hodgkin’s lymphoma or chronic lymphocytic leukemia. Of these patients, 18 had follicular lymphoma, 17 had diffuse large B-cell lymphoma, 16 had mantle cell lymphoma, 18 had T-cell lymphoma, 15 had marginal zone lymphoma and other types, and 16 had chronic lymphocytic leukemia.
Patients had undergone several previous unsuccessful treatment rounds. During the trial, they received 80 mg of oral abexinostat two times a day, four hours apart. The drug was given for 14 days of a three-week cycle, and the treatment was continued until the cancer progressed or patients had unacceptable side effects.
While the median treatment duration was 2.8 months in the entire group, patients with follicular lymphoma continued for a median of 5.6 months.
After 18 months, 87 patients remained in the study for at least one follow-up examination. Among them, the overall response rate was 28%, with 5% having a complete response. The duration of the response was 8.8 months.
The response rates, however, varied among the groups included, with follicular, T-cell, and diffuse large B-cell lymphomas having overall response rates of 56%, 40%, and 31%, respectively.
Likewise, the duration of the response was highest among those with follicular lymphoma, who maintained the response for a median of 16 months. Patients with T-cell and diffuse large B-cell lymphomas had durations of 11.5 months and 1.9 months, respectively.
Nearly all patients experienced adverse events related to the treatment, with 82 percent having grade 3 or more severe side effects. The most common were impacts on blood cell counts, with reductions of platelets, neutrophils, and red blood cells. Five patients died during the study, but none of the deaths could be linked to the treatment.
Since the treatment was given at a fixed dose, the research team explored whether side effects were more common or severe among patients with a lower body surface area. They confirmed that this was the case, indicating that it may be possible to reduce the side effects by reducing the intensity or doses of the treatment.