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.