Safety & Pharmacokinetics Study Of Azacitidine (SC And Oral) In Subjects With MDS, CMML, AML, Lymphoma And Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to compare the amount of drug that gets into the bloodstream between different tablets taken by mouth and an injection under the skin.

Official Title
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A Phase I, Dose-Ranging Study to Evaluate the Pharmacokinetics and Safety of Azacitidine Administered Subcutaneously (SC) and as Different Oral Formulations in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myelogenous Leukemia (AML), Lymphoma, and Multiple Myeloma

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndromes, Lymphoma, Multiple Myeloma, Leukemia, Myelomonocytic, Chronic

Intervention / Treatment
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* Drug: azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Diagnosis of MDS or CMML Diagnosis of AML, Multiple myeloma, Hodgkin's or Non-Hodgkin's lymphoma for whom standard curative or palliative measures do not exist or are no longer effective ECOG Performance Status 0-2 Use of acceptable birth control Standard safety inclusion for serum creatinine, AST, ALT, bilirubin Serum bicarbonate greater than or equal to 20 mEq/L Platelet count greater than or equal to 25,000/uL Hemoglobin greater than or equal to 500/uL Signed informed consent Exclusion Criteria: Diagnosis of acute promyelocytic leukemia Treatment with demethylating agents within 21 days prior to Cycle 1, Day 1 Treatment with any anticancer therapy (standard or investigational) within 21 days prior to Cycle 1, Day 1 or ongoing adverse events from previous treatment Hypersensitivity to azacitidine or mannitol Active, uncontrolled infection Presence of GI disease, malignant tumors or other conditions known to interfere with ADME Known or active HIV, viral hepatitis B or C Breastfeeding or pregnant females Current or uncontrolled cardiac disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>subcutaneous and oral azacitidine Cycle 1 (PK Phase) - Subjects will receive a single SC dose of 75 mg/m2 on Days 1 and 15. Single oral doses of a given formulation of azacitidine will be administered in increasing doses on Days 3 and 5, and at doses calculated to deliver 80% and 120% of the SC exposure, up to a maximum dose of 600 mg on Days 17 and 19. Cycles 2 and beyond - (Treatment phase) Oral azacitidine will be administered in a dose calculated to deliver 100% of the SC exposure up to a maximum of 600 mg on days 1 - 7 of a 28 day cycle. | Drug: azacitidine<br>* Arm 1: Cycle 1 (PK Phase) - Subjects will receive a single SC dose of 75 mg/m2 on Days 1 and 15. Single oral doses of a given formulation of azacitidine will be administered in increasing doses on Days 3 and 5, and at doses calculated to deliver 80% and 120% of the SC exposure, up to a maximum dose of 600 mg on Days 17 and 19. Cycles 2 and beyond - (Treatment phase) Oral azacitidine will be administered in a dose calculated to deliver 100% of the SC exposure up to a maximum of 600 mg on days 1 - 7 of a 28 day cycle. Arm 2: All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.<br>* Other names: Vidaza;|
| Experimental: Arm 2<br>Oral Azacitidine All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle. | Drug: azacitidine<br>* Arm 1: Cycle 1 (PK Phase) - Subjects will receive a single SC dose of 75 mg/m2 on Days 1 and 15. Single oral doses of a given formulation of azacitidine will be administered in increasing doses on Days 3 and 5, and at doses calculated to deliver 80% and 120% of the SC exposure, up to a maximum dose of 600 mg on Days 17 and 19. Cycles 2 and beyond - (Treatment phase) Oral azacitidine will be administered in a dose calculated to deliver 100% of the SC exposure up to a maximum of 600 mg on days 1 - 7 of a 28 day cycle. Arm 2: All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.<br>* Other names: Vidaza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the dose for a given oral formulation that would yield similar exposure [area under the curve (AUC)] to 75 mg/m2 of the subcutaneous formulation. |  | 1 - 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation |  | 1 - 18 months | 
| To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine |  | 1 - 18 months | 
| To assess response rates |  | 1 - 18 months | 
| To assess RBC transfusion independence |  | 1 - 18 months | 
| To investigate the pharmacokinetics of oral azacitidine |  | 1 -18 months | 
| To assess the pharmacodynamic effects of oral azacitidine |  | 1 -18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, Myelodysplastic Syndromes, Lymphoma, Multiple Myeloma, Chronic Myelomonocytic Leukemia (CMML)