A Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin's Lymphoma
Condition: Hodgkin's Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: Entinostat
Intervention description: Entinostat tablets
Intervention MeSH terms: Entinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: The Single Group Assignment is one of three regimens based on the protocol version at the time of enrollment.
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hodgkin's Lymphoma; Relapsed Hodgkin's Lymphoma; Refractory Hodgkin's Lymphoma

Summary:

      This study will evaluate the efficacy and safety of entinostat, SNDX-275, in patients with
      relapsed or refractory Hodgkin's lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologic confirmation of relapsed or refractory classical Hodgkin's lymphoma from
             the last biopsy available. Relapsed disease is defined as progressive disease
             following systematic therapy(ies) with curative intent. Refractory disease is defined
             as disease not responding to or having progressed within 3 months of the last dose of
             most recent systemic therapy.

          2. Must have progressed after, or been ineligible for, stem cell transplantation.

          3. Documented disease that is radiographically measurable (≥ 1.5 cm in the largest
             transverse dimension). If only 1 site of radiographically measurable lesion with the
             longest diameter < 2.5 cm, lesion must be positive by Fluorodeoxyglucose Positron
             Emission Tomography (FDG-PET) or biopsy.

          4. Last dose of cytotoxic chemotherapy must be > 21 days before the first dose of study
             drug.

          5. European Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          6. Age 18 years or older.

          7. Total Bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) and Aspartate Transaminase (AST)
             and Alanine Transaminase (ALT) ≤ 2.5 x ULN, possible exceptions if documented Hodgkin
             Lymphoma (HL) liver involvement.

          8. Serum Creatinine ≤ 1.5 x ULN.

          9. Absolute neutrophil counts of ≥ 1,000/µL, and platelet counts ≥ 50,000/µL

         10. Patients or their legal representative must be able to read, understand, and sign a
             written informed consent

        Exclusion Criteria:

          1. Patients with another active cancer (excluding basal cell carcinoma or CIN/cervical
             carcinoma in situ or melanoma in situ). Prior history of other cancer is allowed,
             excluding active disease within the prior 5 years.

          2. Prior allogeneic stem cell transplantation requiring active immunosuppressive therapy
             within 3 months of registration or with evidence of active Graft Versus Host Disease
             (GVHD).

          3. Pregnant or lactating women. Women of child-bearing potential (WOCBP) must have a
             negative serum pregnancy test prior to start of study drug.

          4. WOCBP and men whose partners are WOCBP must use an acceptable method of contraception
             while enrolled on this study, and for a period of 3 months following the last dose of
             study drug.

          5. Patients with uncontrolled intercurrent illness, active or uncontrolled infections, or
             a fever > 38.5⁰C that has not been evaluated for infection on the day of scheduled
             dosing.

          6. Patients who have been treated with any investigational drug within 28 days prior to
             the first dose of study medication, or who are receiving concurrent treatment with
             other experimental drugs or anti-cancer therapy.

          7. Prior treatment with Histone Deacetylase (HDAC) inhibitors (e.g. valproic acid,
             Zolinza (SAHA), romidepsin (Istodax),and experimental compounds such as MethylGene's
             MCGD0103 and Novartis' LBH589).

          8. History of pericarditis or pericardial effusion that had required medical or surgical
             intervention in the last 6 months, or myocardial infarction or arterial thromboembolic
             events within 6 months, or experiencing severe or unstable angina, or New York Heart
             Association (NYHA) Class III or IV disease or a QTc interval >0.47 seconds.

          9. Known human immunodeficiency virus (HIV) or a history of active Hepatitis B or C as
             evidenced by laboratory abnormalities in addition to positive serology.

         10. Active central nervous system lymphoma and lymphoma with leptomeningeal involvement.

         11. Any condition (e.g., known or suspected poor compliance, psychological instability,
             geographical location, etc) that, in the judgment of the investigator, may affect the
             patient's ability to sign the informed consent and comply with study procedures.

         12. Any condition that will put the patient at undue risk or discomfort as a result of
             adherence to study procedures.

         13. History of gastrointestinal disorders (medical disorder or extensive surgery) that
             could interfere with absorption of study drug.