This Phase I/II trial evaluates the safety and preliminary efficacy of DFP-10917 combined with venetoclax in relapsed or refractory acute myeloid leukemia. DFP-10917 is given as a 14-day continuous IV infusion every 28 days, alongside a 14-day oral course of venetoclax following an initial dose ramp-up. The initial phase tests a starting dose of 4 mg/m²/day of DFP-10917 with 400 mg daily of venetoclax. The Data Monitoring Committee reviews toxicity after one treatment cycle. If DLTs are minimal, more patients are added to confirm safety. If the lower dose level shows tolerability, it proceeds to the Phase II expansion to assess the treatment's effectiveness against leukemia using a Simon's two-stage design, targeting up to 17 participants.
Signed informed consent and ability to comply with protocol requirements.
Histologically or pathologically confirmed diagnosis of acute myeloid leukemia based on World Health Organization classification that has relapsed after, or is refractory to, up to 2 prior induction regimens that may have included intensive chemotherapy (e.g., "7+3" cytarabine and daunorubicin), epigenetic therapy (i.e., azacitidine or decitabine with/without venetoclax), or targeted therapy (e.g., FLT-3, IDH 1/2, BCL-2, monoclonal antibody).
Creatinine clearance >30 mL/min (by Cockcroft-Gault method),
Total serum bilirubin <1.5 × upper limit of normal unless due to Gilbert's syndrome, leukemic organ involvement, hemolysis or considered an effect of regular blood transfusions,
Any >Grade 1 persistent clinically significant toxicities from prior chemotherapy.
Leukemic blast count >25 × 109/L. Hydroxyurea permitted to control leukocytosis.
Known history of human immunodeficiency virus or active hepatitis B or active hepatitis C infection.
Concomitant malignancies for which patients are receiving active therapy at the time of signing consent. Patients with adequately treated basal or squamous cell carcinoma of the skin, adequately treated carcinoma in situ (e.g., cervix), breast cancer receiving adjuvant endocrine therapy or prostate cancer not under active systemic treatment other than hormonal therapy may enroll irrespective of the time of diagnosis, with Medical Monitor approval.
Parallel
DFP-10917
DrugDFP-10917 4 mg/m\^2/day is given as a continuous 14-day intravenous infusion, followed by a 14-day rest in each 28-day cycle.
Venetoclax
DrugVenetoclax 400 mg once daily for 10-14 days, followed by a 14-day rest in each 28-day cycle.
Number of patients with dose-limiting toxicities assessed by CTCAE v5.0.
Number of patients with treatment-related adverse events assessed by CTCAE v5.0.
Recommended Phase 2 dose of DFP-10917 in combination with venetoclax (the dose at which <2 out of 6 patients experience a dose-limiting toxicity during the safety assessment period).
The proportion of patients who achieve complete remission.
The proportion of patients who achieve complete remission or complete remission with incomplete hematologic recovery.
The proportion of patients achieving complete remission or complete remission with incomplete hematologic recovery, and morphologic leukemia-free state.
Overall survival.
Volume of distribution of DFP-10917.
Clearance of DFP-10917.
Time to maximum concentration of venetoclax.
Maximum concentration of venetoclax.
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