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

Acute Myeloid Leukemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01912274
• Other study ID #: MEI-004
• Status: Completed
• Phase: Phase 2
• Start date: December 24, 2013
• Est. completion date: November 8, 2016

Study information

• Verified date: January 2021
• Source: Helsinn Healthcare SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 8, 2016
• Est. primary completion date: November 8, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Pracinostat
Elderly newly diagnosed patients will all receive pracinostat
• Azacitidine
Elderly newly diagnosed patients will all receive azacitadine

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Cooper Hospital	Camden	New Jersey
United States	Medical College of South Carolina-Hollings Cancer Ctr	Charleston	South Carolina
United States	The University of Chicago	Chicago	Illinois
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	City of Hope Comprehensive Cancer Ctr	Duarte	California
United States	MD Anderson	Houston	Texas
United States	Inidana Univ Simon Cancer Center	Indianapolis	Indiana
United States	USC Norrris Cancer Center	Los Angeles	California
United States	Medical College of Wisconsin-Froedtert Cancer Center	Milwaukee	Wisconsin
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Bay Area Cancer Research Group	Pleasant Hill	California
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Mercy Medical Research Center	Springfield	Missouri
United States	Stanford University School of Medicine	Stanford	California
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Helsinn Healthcare SA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall Survival	time from the first day of study drug administration to death	through study completion up to a maximum of three years
Secondary	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
Secondary	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

External Links

•   Sponsor website