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

Sponsor:	Celgene Corporation
Information provided by (Responsible Party):	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00761722

Purpose

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.

Condition	Intervention	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Lymphoma Multiple Myeloma Leukemia, Myelomonocytic, Chronic	Drug: azacitidine	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1, Open-Label, Dose-Ranging Study To Evaluate The Pharmacokinetics and Safety of Azacitidine Administered Subcutaneously and as Different Oral Formulations In Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myelogenous Leukemia (AML), Lymphoma, and Multiple Myeloma(MM)

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia familial acute myeloid leukemia with mutated CEBPA hemophilia

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes

Drug Information available for: Azacitidine

U.S. FDA Resources

Further study details as provided by Celgene Corporation:

Primary Outcome Measures:

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. [ Time Frame: 1 - 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the oral bioavailability of up to 6 different oral formulations in comparison to the subcutaneous formulation [ Time Frame: 1 - 18 months ] [ Designated as safety issue: No ]
To assess the safety and tolerability of subcutaneous and oral formulations of azacitidine [ Time Frame: 1 - 18 months ] [ Designated as safety issue: Yes ]
To assess response rates [ Time Frame: 1 - 18 months ] [ Designated as safety issue: No ]
To assess RBC transfusion independence [ Time Frame: 1 - 18 months ] [ Designated as safety issue: No ]
To investigate the pharmacokinetics of oral azacitidine [ Time Frame: 1 -18 months ] [ Designated as safety issue: No ]
To assess the pharmacodynamic effects of oral azacitidine [ Time Frame: 1 -18 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	September 2008
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1 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 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. Other Name: Vidaza
Experimental: Arm 2 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 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. Other Name: Vidaza

Arms

Assigned Interventions

Experimental: Arm 1

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

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.

Other Name: Vidaza

Experimental: Arm 2

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

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.

Other Name: Vidaza

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00761722

Locations

United States, Kansas
Kansas University Medical Center
Kansas City, Kansas, United States, 66160
United States, Texas
Cancer Care Center of South Texas
San Antonio, Texas, United States, 78229
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Northwest Cancer Specialists
Vancouver, Washington, United States, 98684
North Star Lodge Cancer Center
Yakima, Washington, United States, 98902

Sponsors and Collaborators

Celgene Corporation

Investigators

Study Director:

Jay Backstrom, M.D.

Celgene Corporation

More Information

No publications provided

Responsible Party:	Celgene Corporation
ClinicalTrials.gov Identifier:	NCT00761722 History of Changes
Other Study ID Numbers:	AZA PH US 2008 CL 008
Study First Received:	September 25, 2008
Last Updated:	February 2, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Celgene Corporation:

Acute Myeloid Leukemia
Myelodysplastic Syndromes
Lymphoma
Multiple Myeloma
Chronic Myelomonocytic Leukemia (CMML)

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Chronic
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Lymphoproliferative Disorders

Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Precancerous Conditions
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2012