Safety & Pharmacokinetics Study Of Azacitidine (SC And Oral) In Subjects With MDS, CMML, AML, Lymphoma And Multiple Myeloma
RACE
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
1 other identifier
interventional
31
1 country
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2008
Longer than P75 for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 12, 2008
CompletedFirst Submitted
Initial submission to the registry
September 25, 2008
CompletedFirst Posted
Study publicly available on registry
September 29, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 6, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 7, 2016
CompletedNovember 8, 2019
November 1, 2019
7.7 years
September 25, 2008
November 6, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (6)
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
- +1 more secondary outcomes
Study Arms (2)
Arm 1
EXPERIMENTALsubcutaneous 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.
Arm 2
EXPERIMENTALOral Azacitidine All Cycles - Oral azacitidine will be administered a maximum of 600 mg on Days 1 - 7 of a 28 days cycle.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (11)
California Cancer Care Inc
Greenbrae, California, 94904, United States
Main Cancer Centers of Florida, P.A.
Ocoee, Florida, 34761, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Northwest Cancer Specialists, P.C.
Albuquerque, New Mexico, 87109, United States
Willamette Valley Cancer Institute
Springfield, Oregon, 97477, United States
University of Texas- MD Anderson
Houston, Texas, 77030, United States
Hematology and Oncology Assoc. of South Texas
San Antonio, Texas, 78229, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-4417, United States
Yakima Valley Memorial Hospital/ North Star Lodge
Yakima, Washington, 98902, United States
Related Publications (1)
Laille E, Savona MR, Scott BL, Boyd TE, Dong Q, Skikne B. Pharmacokinetics of different formulations of oral azacitidine (CC-486) and the effect of food and modified gastric pH on pharmacokinetics in subjects with hematologic malignancies. J Clin Pharmacol. 2014 Jun;54(6):630-9. doi: 10.1002/jcph.251. Epub 2014 Jan 18.
PMID: 24374798BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Barry Skikne, MD, FACP, FCP (SA)
Celgene Corporation
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 25, 2008
First Posted
September 29, 2008
Study Start
August 12, 2008
Primary Completion
April 6, 2016
Study Completion
April 7, 2016
Last Updated
November 8, 2019
Record last verified: 2019-11