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

Inclusion Criteria

• •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).
• •(Relapse is defined as reemergence of ≥5% leukemia blasts in bone marrow or ≥1% blasts in peripheral blood 90 days to 24 months after first complete remission or complete remission with incomplete hematologic recovery. Refractory acute myeloid leukemia is defined as persistent disease ≥28 days after initiation of intensive induction therapy (up to 2 induction cycles) or relapse \<90 days after first complete remission or complete remission with incomplete hematologic recover. Refractory disease for patients undergoing hypomethylating agent induction is defined as lack of remission following at least 2 cycles of epigenetic therapy without reduction in bone marrow blast status).
• •Adequate organ function as defined by the following laboratory values:
• •* 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,
• •* Alanine aminotransferase and aspartate aminotransferase \<3 × upper limit of normal, unless due to leukemic organ involvement.
• •Eastern Cooperative Oncology Group performance status of 0, 1, or 2).
• •Projected life expectancy of ≥12 weeks.
• •Female patients of childbearing potential must:
• •* Have a negative serum or urine pregnancy test prior to study treatment initiation.
• •* Agree to use at least 1 highly effective form of contraception during study treatment and for 3 months after the last dose.
• •Male patients with female partners of childbearing potential must -- Agree to use at least 1 highly effective form of contraception during study treatment and for at least 3 months after the last dose.
• •Diagnosis of acute promyelocytic leukemia.
• •Prior exposure to anticancer therapies including chemotherapy, radiotherapy or other investigational therapy, including targeted small molecule agents within 14 days of the first day of study treatment or within 5 half-lives prior to first dose of study treatment. Note that hydroxyurea up to 5 g daily × 3 days is permitted to reduce elevated white blood cell (WBC) count.
• •Venetoclax exposure in more than 1 prior regimen.
• •Prior exposure to biologic agents (e.g., monoclonal antibodies) for anti-neoplastic intent within 14 days prior to first dose of study drug.
• •Prior hematopoietic stem cell transplantation.
• •Malabsorption syndrome or other condition that precludes enteral route of administration.
• •Pregnancy or lactation.
• •Active uncontrolled systemic infection (viral, bacterial, or fungal).
• •Ongoing treatment with strong or moderate CYP3A inhibitors or CYP3A inducers, P-gp inhibitors, or narrow therapeutic index P-gp substrates that cannot be discontinued at least 1 week prior to start of venetoclax dosing excluding antifungal prophylaxis.