Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

A Phase II Open-Label, Single-arm, Two-Stage, Multicenter Trial of Pracinostat in Combination With Azacitidine in Elderly (Age 65 Years or Older) Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

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)

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Pracinostat; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Ctr
    • Los Angeles, California, United States, 90033
      • USC Norrris Cancer Center
    • Pleasant Hill, California, United States, 94523
      • Bay Area Cancer Research Group
    • Stanford, California, United States, 94305-5821
      • Stanford University School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Inidana Univ Simon Cancer Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Mercy Medical Research Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • University of Nebraska Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical College of South Carolina-Hollings Cancer Ctr
  • Texas
    • Dallas, Texas, United States, 75390-9179
      • UT Southwestern Medical Center at Dallas
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin-Froedtert Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pracinostat with azacitadine; 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable	Drug: Pracinostat; Elderly newly diagnosed patients will all receive pracinostat; Other Names: SB939; Drug: Azacitidine; Elderly newly diagnosed patients will all receive azacitadine; Other Names: Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response Rate	Proportion of patients assessed as having achieved a disease response of either CR or CRi or MLFS according to the IWG criteria. CR (ie, complete remission defined as <5% blasts in the bone marrow, no blasts with Auer rods, no extramedullary disease, ANC ≥1000/μL, and platelets ≥100,000/μL must be independent of transfusions for at least 1 week before each assessment). CRi (ie, morphologic complete remission with incomplete blood count recovery, defined as morphologic CR with residual neutropenia (<1,000/μL) or residual thrombocytopenia (<100,000/μL), no extramedullary disease, does not require transfusion independence) MLFS (ie, morphologic leukemia free state, defined as <5% blasts in an aspirate sample with marrow spicules, no extramedullary disease, does not require transfusion independence)	through study completion up to a maximum of three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	proportion of patients with CR plus CRi plus MLFS plus PR plus PRi	through study completion up to a maximum of three years
Complete Cytogenetic Response Plus Molecular Complete Remission	proportion of patients assessed as having complete cytogenetic response (CRc) + molecular complete remission (CRm) to pracinostat plus azacitidine	through study completion up to a maximum of three years
Progression Free Survival	time from the first day of study administration to PD, relapse from CR/CRi/MLFS, lack of efficacy or death.	through study completion up to a maximum of three years
Overall Survival	time from the first day of study drug administration to death	through study completion up to a maximum of three years
Duration of Best Response	The duration of the best response to treatment with pracinostat plus azacitidine was determined by the Investigator for patients who achieved a CR, CRi, or MLFS. The duration was defined as the time from the initial determination of response to the time of relapse, PD, or death, whichever occurred first plus 1 day.	through study completion up to a maximum of 3 years
Duration of Response	The duration of the response to treatment with pracinostat plus azacitidine was determined by the Investigator for patients who achieved a CR, CRi, PR, PRi, or MLFS. The duration was defined as the time from the initial determination of response to the time of relapse, PD, or death, whichever occurred first plus 1 day.	through study completion up to a maximum of three years

Collaborators and Investigators

• Sponsor: Helsinn Healthcare SA

Publications and helpful links

General Publications

• Garcia-Manero G, Abaza Y, Takahashi K, Medeiros BC, Arellano M, Khaled SK, Patnaik M, Odenike O, Sayar H, Tummala M, Patel P, Maness-Harris L, Stuart R, Traer E, Karamlou K, Yacoub A, Ghalie R, Giorgino R, Atallah E. Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study. Blood Adv. 2019 Feb 26;3(4):508-518. doi: 10.1182/bloodadvances.2018027409.

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2013
• Primary Completion (Actual): November 8, 2016
• Study Completion (Actual): November 8, 2016

Study Registration Dates

• First Submitted: July 29, 2013
• First Submitted That Met QC Criteria: July 30, 2013
• First Posted (Estimate): July 31, 2013

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: AML; newly diagnosed; open label; elderly patients; HMA; single arm; nonrandomized
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: MEI-004