A Phase II Study of SGI-110 in Philadelphia-Negative Myeloproliferative Neoplasms
Condition: Myeloproliferative Neoplasms
MeSH terms: Neoplasms; Myeloproliferative Disorders
Intervention: SGI-110
Intervention description: subcutaneously at a dose of 60 mg/m2
Intervention MeSH terms: Guadecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      -  This is an open label single-arm, single-institution stud to evaluate the efficacy and
           safety of SGI-110 in Philadelphia chromosome negative (Ph-) Myeloproliferative Neoplasms
           (MPN) (excluding PV, ET and primary/secondary myelofibrosis). The study will enroll
           approximately 50 patients at the Weill Cornell Medical College.

        -  Enrollment onto this clinical study is expected to be completed in approximately 36
           months. The total study duration will depend on individual response, evidence of disease
           progression and tolerance. Participants will be followed monthly for six months after
           removal from study or until death, whichever occurs first.

      Key eligibility:

        -  Confirmed diagnosis of Ph- MPN and had

        -  No chemotherapy or radiation treatment within 2 weeks prior to study entry.

        -  Subjects meet other protocol-defined criteria related to baseline screening procedures.
    

Eligibility criteria:

        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 <18 years of age, children are excluded
        from this study but may be eligible for future pediatric trials.

        3.1.3 ECOG performance status <3

        3.1.4 Participants must have normal organ function as defined below:

          -  Total bilirubin < or = 1.5 X institutional upper limit of normal unless attributable
             to underlying disease, hemolysis or documented Gilbert's syndrome

          -  AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal unless attributable
             to underlying disease

          -  Creatinine < 1.5add < or = 1.5X institutional upper limit of normal or creatinine
             clearance add using Cockcroft Gault > 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.