Pharmacokinetics and Safety Study of Azacitidine in Cancer Patients With and Without Impaired Renal Function (RENAL)

Inclusion Criteria:

Diagnosis of one of the following:

• MDS according to the FAB classification system (RA, RARS, RAEB, RAEB-T, CMML), AML in remission, malignant solid tumor, MM, NHL, or 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 CNS edema for at least 4 weeks
• Be capable of giving informed consent
• Have an 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/1.73m2 for Cohorts 1, 2, 3, and 4
  • <30 mL/min/1.73m2 for Cohort 5 - Severe renal impairment,
  • 50-80 mL/min/1.73m2 for Cohort 6 - Mild renal impairment,
  • 30 to <50 mL/min/1.73m2 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 HIV, or active hepatitis virus B or C
• Have advanced malignant hepatic tumors
• Have end stage renal disease requiring dialysis