DFP-10917 in Combination With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia

Description

This study is a Phase I/II, open-label trial exploring dosage and expansion cohorts to assess the safety and preliminary efficacy of DFP-10917 in combination with venetoclax for patients with relapsed or refractory acute myeloid leukemia (AML). DFP-10917 will be administered as a 14-day continuous intravenous infusion starting on Day 1, followed by a 14-day rest period, during each 28-day cycle. This will occur concurrently with venetoclax, administered orally at a dose of 400 mg daily for 14 days following a dose ramp-up phase (100 mg and 200 mg on Day 1 and 2, respectively).

In Phase I, the starting dose for DFP-10917 is 4 mg/m²/day, administered concurrently with 400 mg of venetoclax once daily for 14 days (Dose Level 1). The Data Monitoring Committee (DMC) will assess dose-limiting toxicities (DLTs) after three patients are enrolled at this dose level and the last patient has completed the 4-week safety assessment period (i.e., one cycle of the combination regimen). At Dose Level 1 (4 mg/m²/day of DFP-10917 with venetoclax 400 mg daily for 14 days), if none of the three patients experience a DLT, the study will enroll an additional three patients at this dose level to confirm the combination’s safety and tolerability. If one out of three patients experiences a DLT, up to three additional patients may be enrolled. If one or fewer out of six treated patients experience a DLT at Dose Level 1, this dose will be declared the recommended Phase II dose (RP2D) and used in the Phase II expansion cohort. If two or more patients out of the total three to six patients at Dose Level 1 experience a DLT, the study will continue enrollment at Dose Level 1 (4 mg/m²/day of DFP-10917 for 14 days concurrently with venetoclax 400 mg daily for 10 days of each 28-day cycle) to determine the safety and tolerability of Dose Level -1. A patient who discontinues therapy during Cycle 1 without experiencing DLTs is considered evaluable for safety purposes only if all scheduled doses of DFP-10917 and at least 80% of the venetoclax doses were administered in the first cycle. Once the RP2D of DFP-10917 in combination with venetoclax is determined, the expansion cohort will begin enrollment to evaluate the anti-leukemia efficacy of this combination. A Simon’s two-stage min-max design will be employed, with up to 17 patients expected to participate.