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

NCT01912274 | Completed Phase 2 Results DMC

• 1 other identifier: MEI-004
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 17

Brief 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)

Conditions

Acute Myeloid Leukemia

Keywords

AML; open label; nonrandomized; single arm; elderly patients; HMA; newly diagnosed

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Overall Response Rate

  through study completion up to a maximum of three years

• Complete Cytogenetic Response Plus Molecular Complete Remission

  through study completion up to a maximum of three years

• Progression Free Survival

  through study completion up to a maximum of three years

• Overall Survival

  through study completion up to a maximum of three years

• Duration of Best Response

  through study completion up to a maximum of 3 years

Study Arms (1)

Pracinostat with azacitadine

EXPERIMENTAL

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; Drug: Azacitidine

Interventions

Pracinostat DRUG

Elderly newly diagnosed patients will all receive pracinostat

Also known as: SB939

Pracinostat with azacitadine

Azacitidine DRUG

Elderly newly diagnosed patients will all receive azacitadine

Also known as: Vidaza

Pracinostat with azacitadine

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (17)

City of Hope Comprehensive Cancer Ctr

Duarte, California, 91010, United States

Location

USC Norrris Cancer Center

Los Angeles, California, 90033, United States

Location

Bay Area Cancer Research Group

Pleasant Hill, California, 94523, United States

Location

Stanford University School of Medicine

Stanford, California, 94305-5821, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

The University of Chicago

Chicago, Illinois, 60637, United States

Location

Inidana Univ Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Mercy Medical Research Center

Springfield, Missouri, 65807, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

Cooper Hospital

Camden, New Jersey, 08103, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Medical College of South Carolina-Hollings Cancer Ctr

Charleston, South Carolina, 29425, United States

Location

UT Southwestern Medical Center at Dallas

Dallas, Texas, 75390-9179, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin-Froedtert Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 30760466 DERIVED

Related Links

• Sponsor website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

SB939 compound; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Edwin de Wit - Head of Clinical development
• Organization: Helsinn HealthcareSA

info-HHC@helsinn.com

+ 41 919852121

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2013
• First Posted: July 31, 2013
• Study Start: December 24, 2013
• Primary Completion: November 8, 2016
• Study Completion: November 8, 2016
• Last Updated: February 9, 2021
• Results First Posted: February 9, 2021

Record last verified: 2021-01

Locations

US (17)