Todd Michael Cooper
CHICAGO — CPX-351 appeared well-tolerated and effective followed by a chemotherapy regimen among children with relapsed or refractory acute myeloid leukemia, according to results of a phase 1/phase 2 AAML 1421 trial presented at ASCO Annual Meeting.
“These were the best response rates published in North America for [children with AML in first relapse], perhaps in the future this could become a standard,” Todd Michael Cooper, DO, associate professor of pediatrics and director of the pediatric leukemia/lymphoma program at University of Washington School of Medicine, said during his presentation. “These results certainly warrant phase 3 study of CPX-351. In fact, it’s going to be the lead molecule incorporated in the next [Children’s Oncology Group] phase 3 studies.”
Heavily pretreated children with relapsed AML need effective regimens with favorable toxicity, according to study background.
Cooper and colleagues sought to establish the recommended phase 2 dose of CPX-351 (Vyxeos, Jazz Pharmaceuticals), a liposomal preparation of cytarabine and daunorubicin, and response rates after as many as two cycles of treatment (CPX-351 in cycle 1 and fludarabine, cytarabine and granulocyte colony-stimulating factor [FLAG] in cycle 2).
The trial included 38 patients between the ages of 1 and 21 years with relapsed or refractory AML. Researchers assigned six patients to the dose-finding phase and 32 in first relapse to the efficacy phase. They used a modified rolling six design to assess dose-limiting toxicity in the first therapy cycle.
Dose level 1 was 135 units/m2 CPX-351 on days 1, 3 and 5. There was a single-dose de-escalation to 100 units/m2 if dose level 1 appeared intolerable.
Results showed that CPX-351 at dose level 1 — which researchers established as the recommended phase 2 dose — was well-tolerated. Only one patient in the dose-finding phase experiencing a dose-limiting toxicity — a grade 3 decrease in ejection fraction — and all six patients in this phase were eligible for efficacy evaluation. The most common grade 3 or higher toxicities in cycle 1 included fever/neutropenia (45%), infection (47%) and rash (40%). No patients died of toxicities.
Efficacy results after up to two therapy cycles showed a complete response and complete response without platelet recovery rate (CR+CRp) of 68.3% (90% CI, 52.9-78) and an ORR (CR+CRp and complete response with incomplete hematologic recovery) of 81.1% (90% CI, 67.4-88.8).
Best results included 20 complete responses (54%), five complete responses without platelet recovery (14%), and five complete responses with incomplete hematologic recovery (14%). About 70% of patients achieved their best response after cycle 1.
Researchers detected no residual disease by flow symmetry in 21 of the 25 patients who had complete responses or complete responses without platelet recovery.
“We are going to need to look closely at overlapping toxicities ... but we need to be really careful,” Cooper said. “Moving forward we are going to try adding maintenance on top of CPX-351.” – by John DeRosier
Cooper TM, et al. Abstract 10003. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Cooper reports employment, stock and other ownership interests with Celgene and Juno Therapeutics. Please see the abstract for all other authors’ relevant financial disclosures.