A Phase 2a, Open-Label, Two Stage Study of Nerofe or Nerofe With Doxorubicin in Subjects With AML or MDS

A Phase 2a, Open-Label, Two Stage Study: Stage A: Dose-Range Finder Study to Assess the Safety and Efficacy of Two Doses of Nerofe and Two Doses of Nerofe in Combination With Doxorubicin in Subjects With Acute Myelogenous Leukemia or High Risk Myelodysplastic Syndrome (AML/High Risk MDS). Stage B: Dose Confirmation Study to Assess the Safety and Efficacy of Nerofe or Nerofe in Combination With Doxorubicin in Subjects With AML/ High Risk MDS

This is a Phase 2a, Open-label, one arm study in which the eligible patients will be treated with IV Nerofe, three times a week in 28 days cycles (up to 12 cycles).

Evaluation will include safety procedures, blood level of study drug in certain time points, immune system response and tests checking the mechanism of the drug action.

Nerofe is a first-in-class hormone peptide with cancer suppressive properties. It works in three mechanisms of action. The purpose of this research is to study Nerofe's effect in patients diagnosed with AML and MDS.

Inclusion Criteria

1. Males and females ≥18 years of age.

2. Either:

   • AML patients, who are not candidates for aggressive therapy and/or stem cell transplant (usually the elderly patients), or
   • Low and high prognostic risk MDS patients (according to the IPSS-R classification), resistant or relapsing following at least 1 course of hypo-methylation therapy.

3. Anti-tumor (in this case the anti-MDS or anti-leukemic) effect can be measured according to the IWG criteria (Appendices B, C).

4. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

5. Acceptable clinical laboratory values at screening, as indicated by:

   • Absolute neutrophil count ≥ 1,000/mm3;
   • Platelets ≥ 50,000/mm3;
   • Hemoglobin ≥ 6.5 g/dl ;
   • Total bilirubin ≤ 1.5 × the upper limit of normal (ULN);
   • AST (SGOT) ≤ 2.5 × the ULN;
   • ALT (SGPT) ≤ 2.5 × the ULN;
   • Serum creatinine ≤ 1.5 mg/dL or a measured creatinine clearance 60 mL/min and above

6. Negative serum β hCG test in women of childbearing potential

7. Women of childbearing potential must agree to use dual contraceptive methods while on study drug and for 3 months afterward.

8. Men who partner with a woman of childbearing potential must agree to use effective, dual contraceptive methods while on study drug and for 3 months afterward.

9. Willing and able to provide written acceptance that during the trial, bone marrow examination should be performed, with cytogenetics. Bone marrow examination will be performed at Screening, Cycle 3, every odd subsequent cycles and End of Dosing Visit (as per PI and Medical Monitor decision).

10. Bone marrow positive for ST2 receptor expression.

11. Willing and able to provide written Informed Consent and comply with the requirements of the study

Exclusion Criteria

1. Any chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy 30 days prior to study entry and , immunosuppressive therapy, prednisone > 20 mg/day, or any equivalent corticosteroids during the last six months.

2. Erythroid stimulating agents are allowed until one day prior to treatment initiation with study drug.

3. Presence of an acute toxicity of prior chemotherapy, with the exception of alopecia or peripheral neuropathy, that has not resolved to ≤ Grade 2, as determined by NCI CTCAE v 4.0

4. Receipt of >1 prior regimen of genotoxic therapy.

5. Previous bone marrow transplantation.

6. Life expectancy <12 weeks.

7. RBC transfusions for at least 1 week and platelet transfusions for at least 3 days prior to study entry.

8. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness (AIDS).

9. Known active hepatitis B or C or other active liver disease

10. Active infection requiring systemic therapy.

11. Unstable Insulin-dependent diabetes mellitus (IDDM), defined by one or more hospitalization (including ER visits) due to high or low blood glucose levels within the last 6 months.

12. History of any of the following within 12 months prior to initiation of study drug: Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), unstable angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism (within the last 6 month).

13. Uncontrolled hypertension and change in treatment regimen within the last month prior to screening.

14. Risk of syncope, in the judgment of the Principle Investigator, according to the patient's history of Syncope.

15. History of ongoing cardiac dysrhythmias requiring drug treatment.

16. Malignancies during the last yearexcept for skin non-melanomatous tumors and thyroid carcinomas..

17. Any known severe multiple allergy or acute allergic reaction.

18. Use of any investigational agents within 4 weeks or 5 half-lives of initiation of study drug.

19. Pregnant or lactating women.

20. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the patient inappropriate for entry into this study.

    For combination therapy only:

21. Impaired cardiac function defined as left ventricular ejection fraction (LVEF) ≤ 55 % as measured by ECHO.