A Phase 1b/2a, Open-label, Non-randomized Study of Birinapant in Combination With 5-azacitidine in Subjects With Myelodysplastic Syndrome Who Are Refractory or Have Relapsed to 5-azacitidine Therapy

Inclusion Criteria:

- Men or women more than18 years of age.

- Patients with high-risk Myelodysplastic Syndrome

- Performance status of greater or equal to 2 by the Eastern Cooperative Oncology Group
(ECOG) scale.

- Hydroxyurea for patients with rapidly proliferative disease can be used up to 24
hours prior to therapy but not concomitantly with 5-Azacitidine.

- Adequate liver and renal function.

- Women of childbearing potential must have a negative serum pregnancy test at
screening within 48 hours prior to the first dose

- Women of childbearing potential must agree to use 2 methods of adequate contraception

Exclusion Criteria:

- Subjects with life-threatening toxicity or non tolerability to prior 5-Azacitidine
therapy.

- Subjects with hypoplastic Myelodysplastic syndrome.

- Subjects with >30% bone marrow blast cells.

- Subjects with advanced malignant hepatic tumors or second malignancy within 2 years

- Known diagnosis of human immunodeficiency virus or chronic active Hepatitis B or C.

- Uncontrolled hypertension

- Impaired cardiac function, uncontrolled cardiac arrhythmias despite medications,

- QT interval corrected for heart rate (QTcB) more than 480 msec

- Lack of recovery of prior adverse events to Grade ≤1 severity (National Cancer
Institute Common Terminology Criteria for Adverse Events version 4) (except alopecia)
due to therapy administered prior to the initiation of study drug dosing.

- Nursing or pregnant women.

- Known allergy to any of the formulation components of birinapant.

- Known or suspected hypersensitivity to 5-Azacitidine or mannitol.

- Any concurrent disease and/or medical condition that, in the opinion of the
Investigator, would prevent the subject's participation.

- History of Bell's Palsy.