A Study of Rebecsinib for Patients With Relapsed/Refractory Secondary Acute Myeloid Leukemia or High Risk Myelofibrosis

Inclusion Criteria

• •1. Ability to understand and the willingness to sign a written informed consent.
• •2. Must have a refractory myeloid neoplasm (5th Edition WHO Classification of Tumors) consisting of secondary AML (sAML), which has evolved from antecedent MDS, MPN, MDS/MPN, or have higher-risk MF defined by DIPSS Plus or MIPSS70+ version 2.0, and excess bone marrow blasts (\> 5%). Patients with sAML, defined as AML with an antecedent history of MDS or MPN or WHO AML with myelodysplasia related genetic changes or WHO AML with myelodysplasia related cytogenetic abnormalities. Must be ineligible for bone marrow transplantation at the time of enrollment and have relapsed or be refractory or intolerant to available therapies, such as anthracycline chemotherapy, epigenetic modifier therapy (azacytidine or decitabine) or venetoclax including any treatment that is active in specific mutations if relevant (e.g., FLT3 inhibitors for patients with FLT3 mutations). If the patient has not received intensive induction chemotherapy in the past as a result of being unfit for chemotherapy, then the patient must have undergone at least one line of epigenetic modifier or other available therapy. If the patient has received intensive induction therapy, then the patient must have undergone at least two lines of therapy. If a patient has a FLT3 or IDH mutation, prior therapy must include a FLT3 or an IDH inhibitor. Relapse is defined as the recurrence of excess leukemic blasts in the marrow after previously achieving a complete remission, or complete remission with incomplete count recovery. Refractory refers to persistent excess leukemic blasts after two cycles of standard anthracycline containing induction, or one cycle of a high dose cytarabine containing regimen, or one cycle of a non-intensive regimen.
• •3. Calculated Creatinine clearance (CrCl) \> 60 mL/min (based upon the Cockcroft- Gault Equation \[CrCl = (140-age) \* ideal body wt (in kg) \* (0.85 if female) / (72 \* Cr)\]. Estimate Ideal body weight in (kg) Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet. Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.
• •4. Has recovered from the toxic effects of prior therapy to their clinical baseline.
• •5. Subjects must be aged 18 years or older.
• •6. Both men and women of all races and ethnic groups are eligible for this trial.
• •7. Women of childbearing potential (not postmenopausal for at least one year or not surgically incapable of bearing children) must agree not to become pregnant for the duration of the study. Both men and women must agree to use a barrier method of contraception for the duration of the study and until 10 weeks after the final dose of rebecsinib.
• •8. Women of child-bearing potentialmust have a negative serum or urine pregnancy test.
• •9. For sAML and high risk MF, at relapse must have ≥5% leukemic bone marrow blasts.
• •10. Subjects must have an ECOG performance status of 0-2.
• •11. Hemoglobin ≥ 8.0 g/dL. This is to alleviate immediate concomitant need for transfusion via institutional guidelines for transfusion for symptomatic anemia.
• •12. Total bilirubin ≤ 1.5 times upper limit of normal.
• •13. ALT and AST ≤ 1.5 times upper limit of normal
• •14. Prothrombin time international normalized ratio (INR) ≤ 2; AND Partial thromboplastin time ≤ 1.66 times upper limit of normal.