Back to resultsPharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function (RENAL)
Primary Purpose
MDS, AML, Solid Tumors
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
azacitidine
Sponsored by
About this trial
This is an interventional other trial for MDS focused on measuring MDS, AML, Solid Tumors, Azacitidine, PK, Pharmacokinetics, Renal Impairment, Multiple Myeloma, Non-Hodgkin's Lymphoma, Hodgkin's Disease
Eligibility Criteria
Inclusion Criteria:
Diagnosis of one of the following:
- MDS according to the French-American-British (FAB) classification system: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), or chronic myelomonocytic leukemia (CMML); or
- Acute myelogenous leukemia (AML) in remission,
- Malignant solid tumor,
- Multiple myeloma (MM),
- Non-Hodgkin lymphoma (NHL), or
- Hodgkin lymphoma (HD)
- Patients with a history of treated brain metastases should be clinically stable for greater than 4 weeks prior to signing the informed consent form and off glucocorticoid therapy for central nervous system (CNS) edema for at least 4 weeks
- Be capable of giving informed consent
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Have a life expectancy ≥ 3 months
- Have stable renal function for at least 2 months
Have average calculated creatinine clearance of:
- >80 mL/min/1.73m^2 for Cohorts 1, 2, 3, and 4
- <30 mL/min/1.73m^2 for Cohort 5 - Severe renal impairment,
- 50-80 mL/min/1.73m^2 for Cohort 6 - Mild renal impairment,
- 30 to <50 mL/min/1.73m^2 for Cohort 7 - Moderate renal impairment
Have organ and marrow function at the screening and pre-dose visits as defined below:
- Hemoglobin ≥8 g/dL,
- Absolute neutrophil count ≥0.75 x 10^3/µL,
- Platelets ≥30 x 10^3/µL,
- Total bilirubin ≤1.5 times the upper limit of normal (ULN),
- Aspartate aminotransferase (AST) ≤2 times the ULN, and
- Alanine transaminase (ALT) ≤2 times the ULN;
- Have a 12-lead electrocardiogram (ECG) that is not clinically significant, as determined by the Investigator, at screening
Have serum bicarbonate:
- 20 mEq/L for patients with normal renal function (cohorts 1, 2, 3 and 4),
- 16 mEq/L for patients with impaired renal function (cohorts 5, 6 and 7)
- Women of childbearing potential may participate, providing are not pregnant and agree to use at least 2 effective contraceptive methods throughout the study
- Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and to avoid fathering a child for 6 months following the date of the last dose of study medication
- Be a nonsmoker or must not have smoked for at least 30 days before the screening visit and agree to abstain from smoking during study participation
Exclusion Criteria:
- Women who are pregnant or nursing;
- Had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to signing informed consent
- Have been treated with an investigational agent within 4 weeks prior to signing the informed consent form
- Have ongoing clinically significant adverse event(s) due to chemotherapy, radiotherapy or investigational agents administered more than 4 weeks prior to signing the informed consent as determined by the Investigator
- Have known or suspected hypersensitivity to azacitidine or mannitol
- Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
- Have low blood pressure (supine blood pressure <90/60 mmHg)
- Have human immunodeficiency virus (HIV), or active hepatitis virus B or C
- Have advanced malignant hepatic tumors
- Have end stage renal disease requiring dialysis
Sites / Locations
- Sutter East Bay Hospitals
- Palm Springs Research Institute
- MCG Cancer Center
- Joliet Oncology-Hematology Associates, Ltd.
- University of Kentucky-Markey Cancer Center Clinical Research Organization
- Nevada Cancer Institute
- Montefiore Medical Center
- Mid Dakota Clinical P.C. - Cancer Treatment and Research Center
- Gabrail Cancer Center
- Pharma Resource
- Cancer Therapy and Research Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Azacitidine 25 mg/m^2
Azacitidine 50 mg/m^2
Azacitidine 75 mg/m^2
Azacitidine 100 mg/m^2
Severe RI: azacitidine 75 mg/m^2
Arm Description
Participants with normal renal function received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Participants with severe renal impairment (RI; defined as creatinine clearance < 30 mL/min/1.73 m^2) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Outcomes
Primary Outcome Measures
Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point
Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity
The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine after a single dose, calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation:
AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.
Maximum Plasma Concentration of Azacitidine (Cmax)
The maximum observed plasma concentration of azacitidine after a single dose on Day 1.
Time to Maximum Plasma Concentration of Azacitidine (Tmax)
The time to first maximum observed plasma concentration of azacitidine after a single dose on Day 1.
Terminal Phase Half-life of Azacitidine (t½)
The terminal phase half-life of azacitidine after a single dose on Day 1, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.
Apparent Total Clearance of Azacitidine (CL/F)
The apparent total clearance of azacitidine after a single dose on Day 1, calculated as Dose/AUC0-inf.
Apparent Volume of Distribution of Azacitidine (Vz/F)
The apparent volume of distribution of azacitidine after a single dose on Day 1, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz)
Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose After Single and Multiple Doses of Azacitidine
The effect of renal impairment on azacitidine pharmacokinetics was analyzed by comparing PK parameters obtained on Days 1 and 5 from participants with severe renal impairment and those with normal renal function.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule.
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Time Point After Single and Multiple Doses of Azacitidine
The area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule for participants with normal renal function and for participants with severe renal impairment.
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine
The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine, after a single dose (Day 1) and multiple doses (Day 5), calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation:
AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.
Maximum Plasma Concentration of Azacitidine (Cmax) After Single and Multiple Doses of Azacitidine
The maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and for participants with severe renal impairment.
Time to Maximum Plasma Concentration of Azacitidine (Tmax) After Single and Multiple Doses of Azacitidine
The time to first maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment.
Terminal Phase Half-life of Azacitidine (t½) After Single and Multiple Doses of Azacitidine
The terminal phase half-life of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.
Apparent Total Clearance of Azacitidine (CL/F) After Single and Multiple Doses of Azacitidine
The apparent total clearance of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated as Dose/AUC0-inf.
Apparent Volume of Distribution of Azacitidine (Vz/F) After Single and Multiple Doses of Azacitidine
The apparent volume of distribution of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz).
Number of Participants With Adverse Events (AEs)
A serious adverse event is one that at any dose of the study drug or at any time during the period of observation:
Results in death;
Is life threatening;
Requires inpatient hospitalization or prolongation of existing hospitalization;
Results in persistent or significant disability/incapacity;
Is a congenital anomaly/birth defect;
Is medically important.
The Investigator assessed each AE for potential causal relationship between the event and study drug.
The intensity of adverse changes in physical signs or symptoms was graded from 1 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00652626
Brief Title
Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function
Acronym
RENAL
Official Title
A Phase 1, Open-Label, Multi-Center, Parallel Group Study to the Pharmacokinetics and Safety of Subcutaneous Azacitidine in Adult Cancer Patients With and Without Impaired Renal Function
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
November 1, 2008 (Actual)
Primary Completion Date
July 1, 2012 (Actual)
Study Completion Date
July 1, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate three things. The first being whether azacitidine is absorbed in the body at the same rate or proportion for different concentrations. The second is to determine the effect renal impairment has or does not have on the absorption of azacitidine. The third is to determine if azacitidine is safe and well tolerated in patients with renal function impairment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MDS, AML, Solid Tumors, Multiple Myeloma, Non-Hodgkin's Lymphoma, Hodgkin's Disease
Keywords
MDS, AML, Solid Tumors, Azacitidine, PK, Pharmacokinetics, Renal Impairment, Multiple Myeloma, Non-Hodgkin's Lymphoma, Hodgkin's Disease
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Azacitidine 25 mg/m^2
Arm Type
Experimental
Arm Description
Participants with normal renal function received a single subcutaneous dose of azacitidine 25 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Arm Title
Azacitidine 50 mg/m^2
Arm Type
Experimental
Arm Description
Participants with normal renal function received a single subcutaneous dose of azacitidine 50 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Arm Title
Azacitidine 75 mg/m^2
Arm Type
Experimental
Arm Description
Participants with normal renal function received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Arm Title
Azacitidine 100 mg/m^2
Arm Type
Experimental
Arm Description
Participants with normal renal function received a single subcutaneous dose of azacitidine 100 mg/m^2 on Day 1. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Arm Title
Severe RI: azacitidine 75 mg/m^2
Arm Type
Experimental
Arm Description
Participants with severe renal impairment (RI; defined as creatinine clearance < 30 mL/min/1.73 m^2) received subcutaneous doses of azacitidine 75 mg/m^2 on Days 1 to 5. Participants could continue treatment in the extension phase, which allowed up to 6 cycles of treatment with 75 mg/m^2 daily on Days 1-7 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
azacitidine
Other Intervention Name(s)
Vidaza
Primary Outcome Measure Information:
Title
Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose
Description
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point
Description
Area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose of azacitidine on Day 1, calculated by the linear trapezoidal rule.
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity
Description
The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine after a single dose, calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation:
AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Maximum Plasma Concentration of Azacitidine (Cmax)
Description
The maximum observed plasma concentration of azacitidine after a single dose on Day 1.
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Time to Maximum Plasma Concentration of Azacitidine (Tmax)
Description
The time to first maximum observed plasma concentration of azacitidine after a single dose on Day 1.
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Terminal Phase Half-life of Azacitidine (t½)
Description
The terminal phase half-life of azacitidine after a single dose on Day 1, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Apparent Total Clearance of Azacitidine (CL/F)
Description
The apparent total clearance of azacitidine after a single dose on Day 1, calculated as Dose/AUC0-inf.
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Apparent Volume of Distribution of Azacitidine (Vz/F)
Description
The apparent volume of distribution of azacitidine after a single dose on Day 1, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz)
Time Frame
Day 1 at predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose After Single and Multiple Doses of Azacitidine
Description
The effect of renal impairment on azacitidine pharmacokinetics was analyzed by comparing PK parameters obtained on Days 1 and 5 from participants with severe renal impairment and those with normal renal function.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule.
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Time Point After Single and Multiple Doses of Azacitidine
Description
The area under the plasma concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of azacitidine following a single dose (Day 1) and multiple doses (Day 5) was calculated by the linear trapezoidal rule for participants with normal renal function and for participants with severe renal impairment.
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity After Single and Multiple Doses of Azacitidine
Description
The area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) for azacitidine, after a single dose (Day 1) and multiple doses (Day 5), calculated by the linear trapezoidal rule and extrapolated to infinity according to the following equation:
AUC0-inf = AUC0-t + (Ct/ke), where Ct is the last quantifiable concentration and ke = elimination rate constant.
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Maximum Plasma Concentration of Azacitidine (Cmax) After Single and Multiple Doses of Azacitidine
Description
The maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and for participants with severe renal impairment.
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Time to Maximum Plasma Concentration of Azacitidine (Tmax) After Single and Multiple Doses of Azacitidine
Description
The time to first maximum observed plasma concentration of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment.
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Terminal Phase Half-life of Azacitidine (t½) After Single and Multiple Doses of Azacitidine
Description
The terminal phase half-life of azacitidine after a single dose (Day 1) or multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant.
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Apparent Total Clearance of Azacitidine (CL/F) After Single and Multiple Doses of Azacitidine
Description
The apparent total clearance of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated as Dose/AUC0-inf.
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Apparent Volume of Distribution of Azacitidine (Vz/F) After Single and Multiple Doses of Azacitidine
Description
The apparent volume of distribution of azacitidine after a single dose (Day 1) and multiple doses (Day 5) for participants with normal renal function and severe renal impairment, calculated according to the equation: Vz/F = Apparent total clearance (CL/F) / terminal phase rate constant (λz).
Time Frame
Day 1 and Day 5: predose, 5, 15, 30, 45 minutes and 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours post-dose
Title
Number of Participants With Adverse Events (AEs)
Description
A serious adverse event is one that at any dose of the study drug or at any time during the period of observation:
Results in death;
Is life threatening;
Requires inpatient hospitalization or prolongation of existing hospitalization;
Results in persistent or significant disability/incapacity;
Is a congenital anomaly/birth defect;
Is medically important.
The Investigator assessed each AE for potential causal relationship between the event and study drug.
The intensity of adverse changes in physical signs or symptoms was graded from 1 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3, and according to the following: Mild (Grade 1), Moderate (Grade 2), Severe (Grade 3), Life threatening (Grade 4), or Death (Grade 5).
Time Frame
Initial treatment phase: Days 1-11 for participants who received a single dose; Days 1-29 for participants who received multiple doses. Extension treatment period: From the date of first dose until 28 days after the date of last dose (up to 7 months).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of one of the following:
MDS according to the French-American-British (FAB) classification system: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), or chronic myelomonocytic leukemia (CMML); or
Acute myelogenous leukemia (AML) in remission,
Malignant solid tumor,
Multiple myeloma (MM),
Non-Hodgkin lymphoma (NHL), or
Hodgkin lymphoma (HD)
Patients with a history of treated brain metastases should be clinically stable for greater than 4 weeks prior to signing the informed consent form and off glucocorticoid therapy for central nervous system (CNS) edema for at least 4 weeks
Be capable of giving informed consent
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Have a life expectancy ≥ 3 months
Have stable renal function for at least 2 months
Have average calculated creatinine clearance of:
>80 mL/min/1.73m^2 for Cohorts 1, 2, 3, and 4
<30 mL/min/1.73m^2 for Cohort 5 - Severe renal impairment,
50-80 mL/min/1.73m^2 for Cohort 6 - Mild renal impairment,
30 to <50 mL/min/1.73m^2 for Cohort 7 - Moderate renal impairment
Have organ and marrow function at the screening and pre-dose visits as defined below:
Hemoglobin ≥8 g/dL,
Absolute neutrophil count ≥0.75 x 10^3/µL,
Platelets ≥30 x 10^3/µL,
Total bilirubin ≤1.5 times the upper limit of normal (ULN),
Aspartate aminotransferase (AST) ≤2 times the ULN, and
Alanine transaminase (ALT) ≤2 times the ULN;
Have a 12-lead electrocardiogram (ECG) that is not clinically significant, as determined by the Investigator, at screening
Have serum bicarbonate:
20 mEq/L for patients with normal renal function (cohorts 1, 2, 3 and 4),
16 mEq/L for patients with impaired renal function (cohorts 5, 6 and 7)
Women of childbearing potential may participate, providing are not pregnant and agree to use at least 2 effective contraceptive methods throughout the study
Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and to avoid fathering a child for 6 months following the date of the last dose of study medication
Be a nonsmoker or must not have smoked for at least 30 days before the screening visit and agree to abstain from smoking during study participation
Exclusion Criteria:
Women who are pregnant or nursing;
Had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to signing informed consent
Have been treated with an investigational agent within 4 weeks prior to signing the informed consent form
Have ongoing clinically significant adverse event(s) due to chemotherapy, radiotherapy or investigational agents administered more than 4 weeks prior to signing the informed consent as determined by the Investigator
Have known or suspected hypersensitivity to azacitidine or mannitol
Have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
Have low blood pressure (supine blood pressure <90/60 mmHg)
Have human immunodeficiency virus (HIV), or active hepatitis virus B or C
Have advanced malignant hepatic tumors
Have end stage renal disease requiring dialysis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jay Backstrom, MD
Organizational Affiliation
Celgene Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Sutter East Bay Hospitals
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
Palm Springs Research Institute
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33012
Country
United States
Facility Name
MCG Cancer Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Joliet Oncology-Hematology Associates, Ltd.
City
Joliet
State/Province
Illinois
ZIP/Postal Code
60435
Country
United States
Facility Name
University of Kentucky-Markey Cancer Center Clinical Research Organization
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
Nevada Cancer Institute
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89135
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Mid Dakota Clinical P.C. - Cancer Treatment and Research Center
City
Bismarck
State/Province
North Dakota
ZIP/Postal Code
58501
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Pharma Resource
City
East Providence
State/Province
Rhode Island
ZIP/Postal Code
02915
Country
United States
Facility Name
Cancer Therapy and Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30091166
Citation
Wehmeyer J, Zaiss M, Losem C, Schmitz S, Niemeier B, Harde J, Hannig CV, Harich HD, Muller J, Klausmann M, Tessen HW, Potthoff K. Impact of performance status and transfusion dependency on outcome of patients with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic leukemia treated with azacitidine (PIAZA study). Eur J Haematol. 2018 Dec;101(6):766-773. doi: 10.1111/ejh.13160. Epub 2018 Oct 25.
Results Reference
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PubMed Identifier
30442503
Citation
Platzbecker U, Middeke JM, Sockel K, Herbst R, Wolf D, Baldus CD, Oelschlagel U, Mutherig A, Fransecky L, Noppeney R, Bug G, Gotze KS, Kramer A, Bochtler T, Stelljes M, Groth C, Schubert A, Mende M, Stolzel F, Borkmann C, Kubasch AS, von Bonin M, Serve H, Hanel M, Duhrsen U, Schetelig J, Rollig C, Kramer M, Ehninger G, Bornhauser M, Thiede C. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018 Dec;19(12):1668-1679. doi: 10.1016/S1470-2045(18)30580-1. Epub 2018 Nov 12.
Results Reference
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PubMed Identifier
31009835
Citation
Stevens B, Winters A, Gutman JA, Fullerton A, Hemenway G, Schatz D, Miltgen N, Wei Q, Abbasi T, Vali S, Singh NK, Drusbosky L, Cogle CR, Hammes A, Abbott D, Jordan CT, Smith C, Pollyea DA. Sequential azacitidine and lenalidomide for patients with relapsed and refractory acute myeloid leukemia: Clinical results and predictive modeling using computational analysis. Leuk Res. 2019 Jun;81:43-49. doi: 10.1016/j.leukres.2019.04.005. Epub 2019 Apr 13.
Results Reference
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Citation
Laille E, et al. A 2-Part Phase I Study in Patients with Solid or Hematologic Malignancies: Dose Proportionality of Subcutaneous (SC) Azacitidine (AZA) and Pharmacokinetics of SC AZA in Patients with Severe Renal Impairment . Presented at American Society of Hematology 2011, December 10-13, 2011, San Diego, CA. Abstract No. 3480.
Results Reference
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PubMed Identifier
29282890
Citation
Du X, Lai YY, Xiao Z, Liu T, Hu Y, Sun A, Li X, Shen ZX, Jin J, Yu L, Laille E, Dong Q, Songer S, Beach CL. Efficacy, safety and pharmacokinetics of subcutaneous azacitidine in Chinese patients with higher risk myelodysplastic syndromes: Results from a multicenter, single-arm, open-label phase 2 study. Asia Pac J Clin Oncol. 2018 Jun;14(3):270-278. doi: 10.1111/ajco.12835. Epub 2017 Dec 28.
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Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function
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