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

NCT ID: NCT01912274

Last Updated: 2021-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-24
• Study Completion Date: 2016-11-08

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Pracinostat

Intervention Type: DRUG

Elderly newly diagnosed patients will all receive pracinostat

Azacitidine

Intervention Type: DRUG

Elderly newly diagnosed patients will all receive azacitadine

Interventions

Pracinostat

Elderly newly diagnosed patients will all receive pracinostat

Intervention Type: DRUG

Azacitidine

Elderly newly diagnosed patients will all receive azacitadine

Intervention Type: DRUG

Other Intervention Names

SB939; Vidaza

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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinn Healthcare SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillermo Garcia-Manero, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

City of Hope Comprehensive Cancer Ctr

Duarte, California, United States

USC Norrris Cancer Center

Los Angeles, California, United States

Bay Area Cancer Research Group

Pleasant Hill, California, United States

Stanford University School of Medicine

Stanford, California, United States

Emory University

Atlanta, Georgia, United States

The University of Chicago

Chicago, Illinois, United States

Inidana Univ Simon Cancer Center

Indianapolis, Indiana, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Mayo Clinic

Rochester, Minnesota, United States

Mercy Medical Research Center

Springfield, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Cooper Hospital

Camden, New Jersey, United States

Oregon Health and Science University

Portland, Oregon, United States

Medical College of South Carolina-Hollings Cancer Ctr

Charleston, South Carolina, United States

UT Southwestern Medical Center at Dallas

Dallas, Texas, United States

MD Anderson

Houston, Texas, United States

Medical College of Wisconsin-Froedtert Cancer Center

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30760466 (View on PubMed)

Related Links

http://www.meipharma.com

Sponsor website

Other Identifiers

MEI-004

Identifier Type: -

Identifier Source: org_study_id