A phase I study tested low dose clofarabine with escalating doses of entinostat in adults with Philadelphia chromosome-negative, newly diagnosed (ND) or relapsed/refractory (R/R) acute lymphoblastic leukemia or acute biphenotypic leukemia (ALL/ABL). The study found that entinostat plus clofarabine appeared tolerable and active in patients with ND ALL/ABL, although it was less active in R/R patients. The report was published in Leukemia Research.
Lead author, Hetty E. Cathaway, MD, did note that infectious and metabolic complications were more common in older patients compared to younger populations. Additionally, the incidence of hyperglycemia and peripheral neuropathy were not increased by the treatment.
Twenty-eight patients were divided into two arms. Arm A of the study was comprised of patients, either ?60 years with ND ALL/ABL or ?21 years with R/R ALL/ABL, that received repeated three-week cycles of entinostat (4 mg, 6 mg, or 8 mg orally days 1 and 8) and clofarabine (10 mg/m2/day IV for 5 days, days 3–7). Arm B included adults aged 40–59 years with ND ALL/ABL, or patients ?21 years in first relapse, who received entinostat and clofarabine prior to traditional chemotherapy on day 11. Changes in DNA damage, global protein lysine acetylation, myeloid-derived suppressor cells, and monocytes were measured in peripheral blood mononuclear cells before, and during therapy.
The results showed that the overall response rate was 32%, and 50% for ND ALL/ABL. The researchers described that “entinostat increased global protein acetylation and inhibited immunosuppressive monocyte subpopulations, while clofarabine induced DNA damage in all cell subsets examined.” There was one death from sepsis and one death from intracranial bleeding, and there was no severe hyperglycemia and no peripheral neuropathy.
Overall, treatment options are sorely needed for older patients with ALL or ABL who aren’t eligible for intensive chemotherapy. The activity of entinostat combined with clofarabine observed in this small study warrants further study of the combination, concluded the study’s authors