A Study of Brequinar in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

Inclusion Criteria: 1. 1\. Willing and able to provide written informed consent for the trial. 2. Patients 18 years of age or older, with relapsed/refractory AML by World Health Organization classification, T-cell leukemia (T-ALL), bi-lineal leukemia (BLL), or mixed phenotypic acute leukemia (MPAL) and who have exhausted available therapy. 3. ECOG Performance Status 0 to 2. 4. 12-lead ECG with no clinically unacceptable findings; adequate cardiac function/NYHA Class 0 to 2. 5. Adequate hepatic function (unless deemed to be related to underlying leukemia). 1. Direct bilirubin ≤ 2 x ULN 2. ALT ≤ 3 x ULN 3. AST ≤ 3 x ULN 6. Adequate renal function as documented by creatinine clearance ≥ 50 mL/min based on the Cockcroft-Gault equation. 7. In the absence of rapidly proliferative disease, the interval from prior leukemia-directed therapy to first dose of study drug will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents. Use of supportive care measures per institution's standard of care is permitted at any time. 8. The effects of brequinar on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 90 days after completion of brequinar administration. 9. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug. Exclusion Criteria: 1. Patients in need of immediate leukapheresis. 2. Any concurrent uncontrolled clinically significant medical condition, laboratory abnormality, or psychiatric illness that could place the participant at unacceptable risk of study treatment. 3. QTc interval using Fridericia's formula (QTcF) ≥ 470 msec. Participants with a bundle branch block and prolonged QTc interval may be eligible after discussion with the medical monitor. 4. Pre-existing liver disease. 5. The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions: a. Intrathecal chemotherapy for prophylactic use or maintenance of controlled CNS leukemia. 6. Presence of graft versus host disease (GVHD) which requires an equivalent dose of ≥ 0.5 mg/kg/day of prednisone or therapy beyond systemic corticosteroids (e.g. cyclosporine or other calcineurin inhibitors or other immunosuppressive agents used for GVHD). 7. Active cerebrospinal involvement of AML, T-cell leukemia (T-ALL), bi-lineal leukemia (BLL), or mixed phenotypic acute leukemia (MPAL). 8. Diagnosis of acute promyelocytic leukemia (APL) 9. Clinically active hepatitis B (HBV) or hepatitis C (HCV) infection. 10. Severe gastrointestinal or metabolic condition that could interfere with the absorption of oral study medication. 11. Prior malignancy, unless it has not been active or has remained stable for at least 2 years. Participants with treated non-melanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible if definitive treatment for the condition has been completed. Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if at the active surveillance stage, hormonal therapy has been initiated, or the malignancy has been surgically removed or treated with definitive radiotherapy. 12. Nursing women or women of childbearing potential (WOCBP) with a positive pregnancy test. 13. Documented hemoglobinopathy.