Credit: Aaron Logan
A compound that has demonstrated efficacy in older adults with acute myeloid leukemia (AML) may be a viable option for childhood acute lymphoblastic
leukemia (ALL) as well.
The drug, CPX-351, is a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle.
It previously showed promise in a phase 2 trial of AML patients ages 60 to 75 years. Now, preclinical results suggest CPX-351 can work against aggressive
pediatric ALL too.
The research appears in Pediatric Blood & Cancer. It was supported by the National Cancer Institute.
“Cytarabine and anthracyclines such as daunorubicin are commonly used to treat ALL in pediatric patients, and while these drug are very effective in front-line, multidrug, combination chemotherapy regimens, there remains room for improvement, especially in pediatric patients who relapse within 36 months of diagnosis,” said study author Richard Lock, PhD, of Children’s Cancer Institute in Sydney, Australia.
“We are very encouraged by these preclinical results, indicating that the proprietary CPX-351 formulation of cytarabine and daunorubicin may be an important tool to maximize efficacy outcomes in relapsed ALL, and we believe these data substantiate the need for additional, clinical study in pediatric patients.”
Dr Lock and his colleagues studied CPX-351 in mice inoculated with leukemia cells from 5 children who had died from ALL. Three of the children, 2 with B-precursor ALL and 1 with T-cell ALL, had relapsed disease at the time of biopsy.
The researchers inoculated up to 18 mice for each of the 5 leukemia types and then randomized the mice to treatment or control.
The maximum-tolerated dose of CPX-351 was 5 units/kg (corresponding to 5 mg/kg cytarabine and 2.2 mg/kg daunorubicin). This dose provided clinically relevant plasma drug exposure and correlated to the pharmacokinetic properties observed in patients with AML.
The researchers found that all 5 models of ALL were “highly responsive” to CPX-351. In the 4 models of B-precursor ALL, the median group response was a complete response. In the mice inoculated with T-cell ALL, the median group response was a partial response.
Among treated mice, event-free survival ranged from 32.8 days to 41.9 days. And among controls, event-free survival ranged from 2.4 days to 10.8 days.
Dr Lock and his colleagues believe these results suggest CPX-351 may be a promising treatment for ALL and support its testing in pediatric leukemia patients.
CPX-351 is currently under investigation in a phase 3 trial in older patients with high-risk (secondary) AML.
