Ziftomenib, Venetoclax, Azacitidine in Pediatric Relapsed or Refractory Acute Leukemia

The phase I, open-label, single-center, single-arm ZiVA trial will evaluate the combination of ziftomenib, venetoclax, and azacitidine in pediatric patients with KMT2A-rearranged, NPM1-mutated, or NUP98-rearranged acute leukemias, according to a report at the 66th American Society of Hematology Annual Meeting & Exposition

“In this phase I study, we will investigate the potential of the combination of ziftomenib with azacitidine and venetoclax to improve response rate and prolong survival in relapsed and refractory pediatric leukemia,” said David McCall, MD, of MD Anderson in Bellaire, Texas.

A cohort of 12 patients is planned for the dose-escalation trial. Once a recommended phase II dose has been established, a 10-patient dose expansion cohort will further evaluate the combination at that dose.

Participants will receive azacitidine 75 mg/m² on days one through five and venetoclax 400 mg/m² on days one through 14 of 28-day treatment cycles. Ziftomenib will be administered continuously, starting on day eight of cycle one. Patients meeting eligibility criteria after a treatment cycle will have the option to receive ziftomenib monotherapy as a bridge to stem cell transplant and as maintenance thereafter.

The primary endpoint is the safety, tolerability, and recommended phase II dose of ziftomenib, venetoclax, and azacitidine. Secondary efficacy endpoints include overall response, overall survival, event-free survival, and duration of response. Exploratory analyses will also seek molecular and cellular markers that are predictive of antitumor activity or treatment resistance, and associations between pharmacokinetics and clinical outcomes will be investigated.

“An almost all-oral regimen would also facilitate delivery of care, save time for patients by minimizing infusions, in addition to lower healthcare costs from decreased utilization of recourses,” added Dr. McCall.

Reference

McCall D, Cuglievan B, Gibson A, et al. A phase I study investigating the combination of the ziftomenib, venetoclax and azacitidine (ZiVA) in pediatric relapsed and refractory acute leukemias. Abstract #1504.4. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.