An Efficacy and Safety Study Of Pracinostat In Combination With Azacitidine In Adults With Acute Myeloid Leukemia


About this study

This is a Phase III, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (AZA) as background therapy in patients ≥ 18 years of age with newly diagnosed acute myeloid leukemia (AML), excluding acute promyelocytic leukemia and cytogenetic low-risk AML, who are unfit to receive intensive remission induction chemotherapy due to age ≥ 75 years or comorbidities. Patients will be randomized in a 1:1 ratio to one of two groups: Group A (experimental group) to receive pracinostat plus AZA and Group B (control group) to receive placebo plus AZA. Randomization will be stratified by cytogenetic risk category (intermediate vs. unfavorable-risk, according to SWOG Cytogenetic Risk Category Definitions) and ECOG performance status (0-1 vs. 2). Treatments will be administered based on 28-day cycles, with pracinostat/placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and AZA administered for 7 days of each cycle. Study treatment should continue until there is documented disease progression, relapse from complete remission (CR), or non-manageable toxicity. A minimum of 6 cycles may be required to achieve a complete remission. Once permanently discontinued from study treatment, patients will enter the Long-term Follow-up phase of the study and will be followed for assessment of disease progression, if applicable, and survival every 3 months (±1 month) until death. The end of this study is defined when 390 events (deaths) have occurred and the study is unblinded for final overall survival analysis. Patients who are receiving study treatment at the end of the study may have the opportunity to continue to receive the study drugs to which they were randomized to (Post- Study Observation Period), until the Sponsor informs the Investigators of the appropriate course of action based on the study results. The Post-Study Observation Period is defined as the period starting from the end of the study for a maximum of 12 months.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female patients ≥ 18 years of age with newly diagnosed, histologically or cytologically confirmed, AML including de novo, secondary to antecedent hematologic disorders, or treatment-related disease with intermediate or unfavorable risk cytogenetics.
  • Unable to receive intensive chemotherapy regimens at enrollment, based on one of the following:
    • I. Age ≥ 75 years;
    • II. Age < 75 years with at least 1 of the following co-morbidities:
      • An ECOG performance status of 2;
      • Clinically significant cardiovascular disease defined as:
        • Left ventricular ejection fraction (LVEF) ≤ 50% measured within 3 months prior to Day 1, confirmed by ECHO/MUGA;
        • Congestive heart failure requiring medical therapy;
        • Chronic stable angina requiring medical therapy;
        • Prior cerebrovascular accident with sequelae.
      • Clinically significant pulmonary disease defined as:
        • Forced expiratory volume in 1 second (FEV1) ≤ 65% of expected;
        • Lung diffusing capacity for carbon monoxide (DLCO) ≤ 65% of expected;
        • Confirmed by pulmonary tests within 3 months prior to Day 1.
      • Diabetes mellitus with symptomatic end-organ damage (e.g., retinopathy, nephropathy, neuropathy, vasculopathy).
      • Autoimmune inflammatory conditions (e.g., rheumatoid arthritis, systemic lupus erythematous, inflammatory bowel disease, or similar) requiring chronic disease modifying therapy (e.g., etanercept, adalimumab, infliximab, rituximab, ethotrexate, or similar).
      • Class III obesity defined as a Body Mass Index (BMI) > 40 kg/m2.
      • Renal impairment defined as serum creatinine > 1.3 mg/dL (> 115 μmol/L) or creatinine clearance < 70 mL/min, but still fulfilling criterion #7.
  • ≥ 20% blasts in bone marrow.
  • Peripheral white blood cell (WBC) count < 30,000/μL:
    • For cyto-reduction, hydroxyurea is allowed during screening and up to Cycle 1, Days 1-14, to reduce WBC count to < 30,000 μL prior to Day 1;
    • After Cycle 1, Day 14, hydroxyurea is prohibited.
  • ECOG performance status ≤2.
  • Adequate organ function as evidenced by the following laboratory findings:
    • Total bilirubin < 2 × upper limit of normal (ULN) or < 3 × ULN for patients with Gilbert-Meulengracht Syndrome;
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN.
  • Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min according to institutional standards.
  • QT-interval corrected according to Fridericia’s formula (QTcF) ≤450 ms on electrocardiogram (ECG) at Screening.
  • Male patient who is surgically sterile, or male patient who is willing to agree with the true abstinence (refrain from heterosexual intercourse) or who uses barrier contraceptive measures during the entire study treatment period and for 3 months after the last administration of study drug, and agree to refrain from donating sperm during the entire study treatment period and for 3 months after the last administration of study drug.
  • Female patient who is of childbearing potential willing to use a highly effective contraceptive measure while participating on study, or willing to agree with the true abstinence from heterosexual intercourse during the entire study treatment period and for 3 months after the last administration of study drug.
  • Female patient who is of childbearing potential must have a negative serum pregnancy test result within 1 week prior to starting study drugs.
  • Willing to provide voluntary written informed consent before performance of any study related procedure not part of normal medical care.
  • Willing and able to understand the nature of this study and to comply with the study and follow-up procedures.

Exclusion Criteria:

  • Able to receive intensive induction chemotherapy.
  • AML-associated inv(16)/t(16;16)/del(16q), t(15;17) (i.e. promyelocytic leukemia) with/without secondary aberrations; t(8;21) lacking del (9q) or complex karyotypes.
  • Presence of an active malignant disease within the last 12 months, with the exception of adequately treated cervical cancer in-situ, non-melanoma skin cancer and superficial bladder tumors (Ta [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]). Other malignancies may be considered after consultation with the Medical Monitor.
  • Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the patient's safety or put the study outcomes at risk.
  • Uncontrolled arrhythmias; any Class 3-4 cardiac diseases as defined by the New York Heart Association (NYHA) functional classification.
  • Evidence of AML central nervous system (CNS) involvement.
  • Previous chemotherapy for AML except for the following, which are allowed:
    • Hydroxyurea for cytoreduction;
    • One course of hypomethylating agent therapy (i.e.; up to 7 doses of azacitidine or 3-5 days of decitabine) within 30 days prior to enrollment (Day 1);
    • Received prior treatment with a hypomethylating agent, except as allowed above.
  • Use of experimental drugs ≤ 30 days prior to screening.
  • Received prior HDAC inhibitor therapy.
  • Known hypersensitivity to any components of pracinostat, azacitidine, or mannitol.
  • Human immunodeficiency virus (HIV) infection or an active and uncontrolled infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
  • Gastrointestinal (GI) tract disease that causes an inability to take oral medication, malabsorption syndrome, or 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 pracinostat and/or AZA, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient inappropriate for this study.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Kebede Begna, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

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