Clinical trial NCT01912274: Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: AML
open label
nonrandomized
single arm
elderly patients
HMA
newly diagnosed
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
First posted: 2013-07-31
Enrollment: 50
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


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.

Primary outcomes:
measure: Best Response Rate
timeFrame: through study completion up to a maximum of three years
Secondary outcomes:
measure: Overall Response Rate
timeFrame: through study completion up to a maximum of three years
measure: Complete Cytogenetic Response Plus Molecular Complete Remission
timeFrame: through study completion up to a maximum of three years
measure: Progression Free Survival
timeFrame: through study completion up to a maximum of three years
measure: Overall Survival
timeFrame: through study completion up to a maximum of three years
measure: Duration of Best Response
timeFrame: through study completion up to a maximum of 3 years
measure: Duration of Response
timeFrame: through study completion up to a maximum of three years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Ctr
state: California
city: Los Angeles
country: United States
facility: USC Norrris Cancer Center
state: California
city: Pleasant Hill
country: United States
facility: Bay Area Cancer Research Group
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Inidana Univ Simon Cancer Center
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Springfield
country: United States
facility: Mercy Medical Research Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Camden
country: United States
facility: Cooper Hospital
state: New Jersey
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charleston
country: United States
facility: Medical College of South Carolina-Hollings Cancer Ctr
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin-Froedtert Cancer Center
state: Wisconsin
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Guillermo Garcia-Manero, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.