A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome

Inclusion Criteria

• •Written informed consent
• •Age ≥ 18 years
• •Diagnosis of MDS (de novo or secondary) by bone marrow aspirate based on the World Health Organization (WHO) classification - Low and Intermediate-1 risk categories MDS using the IPSS (International Prognostic Scoring System)
• •AZA/decitabine (this applies to standard of care and investigational drugs) failure (Dose confirming and Dose expansion parts):
• •defined as discontinuation due to any of the following:
• •* Lack of response after at least 4 cycles
• •* Loss of response (patient must have received therapy for at least 4 cycles)
• •* Progressive disease
• •* Adverse events
• •HMA Naïve group:
• •* Never received a hypomethylating agent for MDS
• •* Failed or ceased to respond to ESA(s)
• •* ESA ineligible; defined as endogenous serum erythropoietin level \> 200 U/L for subjects not previously treated with ESAs
• •Red blood cell transfusion dependent defined as ≥ 2 Red blood cells (RBC) units required in the 8 weeks prior to starting in the study. In addition, there should be no 8 consecutive weeks without red blood cell transfusions in the 16 weeks prior to enrolment.
• •Life expectancy ≥ 3 months
• •Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-2
• •Serum bilirubin levels ≤2 x upper limits of normal (ULN)
• •Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2.5 x ULN
• •Prior history of acute leukemia or AML
• •Unable/unwilling to undergo bone marrow sampling
• •Prior history of bone marrow transplantation
• •Prior malignancy (other than non-invasive malignancy including in situ cervical cancer, Bowen's disease, basal cell cancer of the skin and non-invasive or excised skin squamous cell carcinoma) unless treated with curative intent and without evidence of disease for 3 years before randomization
• •Active viral or bacterial infections: this includes any infections that are being actively treated even if the signs and symptoms appear to have resolved. Courses of antibiotics or anti-viral treatment should be completed before the patients is enrolled
• •Unstable angina, congestive heart failure \[NYHA (New York Heart Association) \>class II\], uncontrolled hypertension \[diastolic \> 100 mmHg\], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction, uncontrolled diabetes mellitus
• •Clinical Evidence of Central Nervous System (CNS) disease
• •Less than 4 weeks since any therapy for MDS
• •Prior history of anaphylaxis to similar products
• •History or presence of a medical condition or disease or substance abuse that in the investigator's assessment would place the patient at an unacceptable risk for study participation
• •Lactating or pregnant woman