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

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