A Phase II Study of SGI-110 in Philadelphia-Negative Myeloproliferative Neoplasms

Inclusion Criteria

3.1.1 Participants must have confirmed diagnosis of Philadelphia chromosome negative MPN neoplasm based on WHO classification (reference) including Chronic Neutrophilic Leukemia (CNL), atypical Chronic Myeloid Leukemia (aCML), Chronic Myelomonocytic Leukemia (CMML), MPN/MDS overlap syndromes, accelerated phase myelofibrosis and MPN unclassifiable.

3.1.2 Age minimum of 18 years. Because no dosing or adverse event data are currently available on the use of SGI-110 in participants 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.

• LVEF < 40 % is allowed as long as there is no NY class III/IV heart failure or uncontrolled arrhythmias.

3.1.5 The effects of SGI-110 on the developing human fetus are unknown. For this reason and because oncological agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

3.1.6 Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

3.2.1 Participants who have had any chemotherapy (investigational or FDA approved) (hydroxyurea is permitted) or radiotherapy within 2 weeks prior to study entry or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.

3.2.2 Participants may not be treated with any other investigational agents while on this study unless approved by the principal investigator AND the sponsors of BOTH investigational agents.

3.2.3 History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine or SGI-110.

3.2.4 Uncontrolled intercurrent illness including, but not limited to, infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Pregnant women are excluded from this study because SGI-110 is a hypomethylating agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with SGI-110, breastfeeding should be discontinued.

3.2.5 Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.