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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT00761722

Collaborator

(none)

Enrollment

Locations

Arms

91.8

Actual Duration (Months)

2.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Lymphoma Multiple Myeloma Leukemia, Myelomonocytic, Chronic	Drug: azacitidine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 12, 2008

Actual Primary Completion Date :

Apr 6, 2016

Actual Study Completion Date :

Apr 7, 2016

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: Vidaza

Arm

Intervention/Treatment

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 Names:

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

Other Names:

Vidaza

Outcome Measures

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. [1 - 18 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	California Cancer Care Inc	Greenbrae	California	United States	94904
2	Main Cancer Centers of Florida, P.A.	Ocoee	Florida	United States	34761
3	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
4	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
5	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
6	Northwest Cancer Specialists, P.C.	Albuquerque	New Mexico	United States	87109
7	Willamette Valley Cancer Institute	Springfield	Oregon	United States	97477
8	University of Texas- MD Anderson	Houston	Texas	United States	77030
9	Hematology and Oncology Assoc. of South Texas	San Antonio	Texas	United States	78229
10	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-4417
11	Yakima Valley Memorial Hospital/ North Star Lodge	Yakima	Washington	United States	98902