Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Pracinostat; Azacitidine
Intervention description: Elderly newly diagnosed patients will all receive pracinostat; Elderly newly diagnosed patients will all receive azacitadine
Intervention MeSH terms: Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: AML; open label; nonrandomized; single arm; elderly patients; HMA; newly diagnosed

Summary:

      The purpose of this study is to determine the safety and effectiveness of pracinostat when
      combined with azacitadine for patients who are 65 years of age or older and have Acute
      Myelogenous Leukemia (AML)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects aged ≥65 years.

          -  Voluntary written informed consent before performance of any study related procedure
             not part of normal medical care.

          -  Newly diagnosed de novo, secondary, or treatment-related AML with intermediate or
             unfavorable-risk cytogenetics based on the Southwest Oncology Group (SWOG)
             classifications (Slovak et al, 2000).

          -  One prior cycle of therapy with an approved hypomethylating agent (HMA) such as
             azacitidine or decitabine is allowed for either an antecedent hematologic disorder
             (AHD) or AML. Patients are also eligible if they have received lenolidamide,
             immunosuppressive therapy or low dose chemotherapy for their AHD. Prior hydroxyurea is
             allowed.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

          -  ≥20% blasts in bone marrow.

          -  Peripheral WBC <30,000/uL.

          -  Adequate organ function as evidenced by:

          -  Total bilirubin 2x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)2.5x ULN

          -  Serum creatinine 2x ULN

          -  QT interval corrected according to Fridericia's formula (QTcF) ≤450 milliseconds (ms)
             for male subjects or ≤470 ms for female subjects on ECG at Screening.

          -  Male subjects who are surgically sterile or willing to use adequate contraceptive
             measures or abstain from heterosexual intercourse during the entire study treatment
             period.

          -  Female subjects who are not of childbearing potential.

          -  Willingness and ability to understand the nature of this study and to comply with the
             study and follow up procedures

        Exclusion Criteria:

          -  Acute promyelocytic leukemia (French-American-British [FAB] M3 classification).

          -  Known AML-associated t(15;17), t(8;21), t(16;16), del(16q), or inv(16) karyotype
             abnormalities.

          -  Presence of a malignant disease within the last 12 months, with the exception of
             adequately treated in-situ carcinomas, basal or squamous cell carcinoma, or
             non-melanomatous skin cancer. Other malignancies will be considered on a case-by-case
             basis.

          -  Life-threatening illnesses other than AML, uncontrolled medical conditions or organ
             system dysfunction that, in the Investigator's opinion, could compromise the subject's
             safety, or put the study outcomes at risk.

          -  Uncontrolled or symptomatic arrhythmias, unstable angina, or any Class 3 or 4 cardiac
             diseases as defined by the New York Heart Association (NYHA) Functional
             Classification.

          -  Clinical evidence of central nervous system (CNS) involvement.

          -  Are candidates for intensive chemotherapy (induction chemotherapy, bone marrow, or
             stem cell transplant) within the next 4 months.

          -  Received more than one prior cycle of HMA, previous bone marrow transplant or other
             intensive chemotherapy regimens for either an AHD or AML.

          -  Received prior radiation therapy for extramedullary disease within 2 weeks of study
             enrollment.

          -  Received prior histone deacetylase (HDAC) inhibitor or deacetylase (DAC) inhibitor is
             not permitted such as Istodax (romidepsin/depsipetide) or valproic acid.

          -  Received hematopoietic growth factors: erythropoietin, granulocyte colony stimulating
             factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), or
             thrombopoietin receptor agonists within 7 days (14 days for Aranesp) prior to study
             enrollment.

          -  Have been treated with any chemotherapeutic agent within 2 weeks or 5 half-lives of
             the first dose of study drug, whichever is longer.

          -  Are being treated with systemic corticosteroids. Inhaled and topical steroids as well
             as intermittent dexamethasone for nausea or vomiting are permitted.

          -  Known history of human immunodeficiency virus (HIV) or active infection with hepatitis
             C virus (HCV) or hepatitis B virus (HBV).

          -  Uncontrolled active systemic infections.

          -  Gastrointestinal (GI) tract disease, causing the inability to take oral medication,
             malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
             affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's disease,
             ulcerative colitis).

          -  Any disease(s), psychiatric condition, metabolic dysfunction, or findings from a
             physical examination or clinical laboratory test result that would cause reasonable
             suspicion of a disease or condition, that contraindicates the use of study drugs, that
             may increase the risk associated with study participation, that may affect the
             interpretation of the results, or that would make the subject inappropriate for this
             study.