Clinical trial NCT05209295: A Study to Evaluate CC-486/Onureg in Participants With Moderate or Severe Hepatic Impairment Compared With Normal Hepatic Function in Participants With Myeloid Malignancies
Official title: A Phase 1, Multicenter, Open-label Study to Evaluate the Pharmacokinetics of CC-486 (Onureg®) in Subjects With Moderate or Severe Hepatic Impairment Compared With Normal Hepatic Function in Adult Subjects With Myeloid Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatic Insufficiency
Neoplasms
Keywords: CC-486
Azacitidine
Hepatic Impairment
Onureg
Myeloid Malignancies
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2022-01-26
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the effect of moderate or severe liver impairment on the drug levels of oral azacitidine and the safety and tolerability of oral azacitidine in participants with myeloid malignancies.


Eligibility criteria: Inclusion Criteria:

* Documented diagnosis of Myelodysplastic syndrome, Acute myeloid leukemia, Non-acute promyelocytic leukemia, Chronic myelomonocytic leukemia, Philadelphia-negative myeloproliferative neoplasms, Myelodysplastic syndrome Myeloproliferative neoplasms overlap, Accelerated phase and blast phase Myeloproliferative neoplasms, Blastic plasmacytoid dendritic cell neoplasm according to the World Health Organization (WHO) 2016 classification
* Life expectancy of ≥ 3 months
* Stable renal function without dialysis for at least 2 months prior to investigational product administration
* Has moderate or severe hepatic impairment as defined by National Cancer Institute Organ Dysfunction Working Group criteria

Exclusion Criteria:

* Chemotherapy or radiotherapy within 2 weeks or 5 half-lives, whichever is longer, prior to the first day of investigational product administration
* Persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to \< Grade 2
* Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study
* History of inflammatory bowel disease, celiac disease, prior gastrectomy, gastric bypass, upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption of the investigational product and/or predispose the participant to an increased risk of gastrointestinal toxicity

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: AUC0-t: Estimation of area under the plasma concentration-time curve (AUC) calculated from time zero to the last measured time point
timeFrame: Day 1
measure: AUC0-∞: Estimation of AUC calculated from time zero to infinity
timeFrame: Day 1
measure: Cmax: Observed maximum concentration
timeFrame: Day 1
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 9 Months
measure: Incidence of serious adverse events
timeFrame: Up to 9 Months
measure: Number of participants with clinically significant changes in electrocardiogram parameters
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in vital signs: Body temperature
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in vital signs: Respiratory rate
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in vital signs: Blood pressure
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in vital signs: Heart rate
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Up to 9 Months
measure: Number of Participants with clinically significant changes in Eastern Cooperative Oncology Group (ECOG) performance status
timeFrame: Up to 9 Months
measure: Incidence of clinically significant changes in clinical laboratory results: Liver Function tests
timeFrame: Up to 9 Months
measure: Number of clinically significant changes in physical examinations
timeFrame: Up to 9 Months
measure: Number of participants with a recording of concomitant medications
timeFrame: Up to 9 Months
measure: Number of participants with a recording of concomitant procedures
timeFrame: Up to 9 Months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: Tulane Cancer Center
state: Louisiana
city: Worcester
country: United States
facility: Local Institution - 0068
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Port Jefferson Station
country: United States
facility: Local Institution - 0007
state: New York
city: Cleveland
country: United States
facility: Local Institution
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Pilar
country: Argentina
facility: Hospital Universitario Austral
state: Buenos Aires
city: ABB
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Hospital Aleman
state: Ciudad Autónoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Clínica Zabala
city: Bogota
country: Colombia
facility: Instituto Nacional De Cancerologia
state: Cundinamarca
city: Bogotá
country: Colombia
facility: Fundacion Ctic Centro de Tratamiento E Investigacion Sobre Cancer Luis Carlos Sarmiento Angulo
state: Distrito Capital De Bogotá
city: Piedecuesta
country: Colombia
facility: Fundación Cardiovascular de Colombia
state: Santander
city: Augsburg
country: Germany
facility: Klinikum Augsburg
state: Bayern
city: Halle
country: Germany
facility: Local Institution - 0075
state: Sachsen-Anhalt
city: Hamburg
country: Germany
facility: Local Institution - 0074
city: Thessaloniki
country: Greece
facility: Local Institution - 9000
city: Badalona
country: Spain
facility: Local Institution - 0018
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Salamanca
country: Spain
facility: Local Institution - 0078
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: