A Study of DSP-5336 in Relapsed/refractory AML/ ALL with or Without MLL Rearrangement or NPM1 Mutation

Exclusion Criteria

1. Has a left ventricular ejection fraction (LVEF) <45%, as determined by ECHO

2. Histological diagnosis of acute promyelocytic leukemia

3. Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP 5336

4. Has had abnormal ECGs that are clinically significant, such as QT prolongation (QTc >450 msec for males and >470 msec for females, with QTc corrected according to Fridericia's formula [QTcF])

5. Has an active, uncontrolled, bacterial, viral, or fungal infection requiring systemic therapy

6. Receives concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5, including specifically: ketoconazole and itraconazole. Other antifungals that are used as standard of care to prevent or treat infections are permitted. If a patient is on one of the excluded azole class antifungals, he/she can be taken off or switched to a permitted azole 7 or more days prior to first dose, then the patient could be allowed on study (Arm B) with approval of the medical monitor.

7. Received immunotherapy, including tumor vaccines and checkpoint inhibitors, within 42 days prior to the first dose of DSP-5336

8. Has been on other investigational treatment within the previous 4 weeks prior to the first dose of DSP-5336

9. Had major surgery within 28 days prior to the first dose of DSP-5336

10. Has active central nervous system leukemia

11. Previously received menin-MLL inhibitors

12. Has immediately life threatening or severe complications of leukemia

13. Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336

14. Received a donor lymphocyte infusion within 28 days prior to the first dose of DSP-5336, or receiving immunosuppressive therapy post-HSCT at the time of screening, or with clinically active GVHD or GVHD requiring active medical intervention other than the use of topical steroids for ongoing cutaneous GVHD

15. Received antineoplastic agents (except hormonal therapies as adjuvant maintenance for breast or prostate cancers if a patient is taking before starting study treatment, and hydroxyurea given for controlling blast cells) within 14 days prior to the first dose of DSP-5336

16. Received anthracycline where cumulative doses exceeded the upper limit per the label approved in each country or investigator discretion (if there is no label restriction, investigator must state the cumulative dose received for each patient and sign to indicate that, in his/her medical opinion, stated prior dose of the agent does not put patient at undue risk of anthracycline-related cardiotoxicity

17. In the opinion of the treating investigator, have any concurrent conditions that could pose an undue medical hazard or interfere with interpretation of study results; these conditions include, but are not limited to: clinically significant non-healing or healing wounds; concurrent congestive heart failure; concurrent unstable angina; concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation); recent (within the prior 6 months) myocardial infarction; acute coronary syndrome within the previous 6 months; significant pulmonary disease (shortness of breath at rest or on mild exertion), eg, due to concurrent severe obstructive pulmonary disease, concurrent hypertension not controlled with concomitant medication, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 6 months

18. Have an active acute or chronic infection, including human immunodeficiency virus (HIV) as determined by anti-HIV antibodies; and hepatitis B virus (HBV) or hepatitis C virus (HCV) as determined by hepatitis B surface antigen (HBsAg) or anti-HCV antibodies, respectively.

    For sites in Japan only: Hepatitis B core (HBc) antibody or hepatitis B surface (HBs) antibody test should be performed if HBsAg is negative. If HBc antibody or HBs antibody test is positive, HBV DNA quantification test should be performed to confirm that HBV DNA is negative.

19. Have advanced liver disease or cirrhosis (Child-Pugh's Class B or greater)

20. Have one or more active autoimmune diseases requiring immunosuppressive therapy other than low-dose corticosteroids (equivalent to prednisone 10mg daily) or azathioprine. Patients on stable immunomodulatory medications may be considered by the investigator

21. Have active (uncontrolled, metastatic) malignancies of another type

22. Have severe dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally, including the inability to swallow oral medication

23. Have cognitive, psychologic, or psychosocial impediment that would impair the ability of the patient o receive therapy according to the protocol, or adversely affect the ability of the patient to comply with the informed consent process, protocol, or protocol-required visits and procedures

24. Are pregnant or breastfeeding or planning to become pregnant Note: Patients who are breastfeeding may be enrolled if they interrupt breastfeeding prior to the first dose of any study drugs and do not feed the baby with breast milk expressed after receiving the first dose of any study drugs. Breastfeeding should not be resumed for at least 6 months after the last dose of study drug

25. Have any history or complication of interstitial lung disease (for sites in Japan only)

26. Have a history of Torsades de Pointes