Escalation Study to Determine Bioavailability of a Single Oral Dose of Decitabine in Patients With Myelodysplastic Syndrome (MDS)
Primary Purpose
Myelodysplastic Syndrome
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
decitabine
decitabine
decitabine
decitabine
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring MDS
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed de novo or secondary MDS.
- Age greater than or equal to 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Adequate renal and hepatic function (creatinine less than or equal to 2.0 mg/dL, total bilirubin less than 2.0 mg/dL, aspartate aminotransferase [AST] or alanine aminotransferase [ALT] less than 3 times the upper limit of normal).
- Life expectancy of at least 6 weeks.
- If currently receiving 5 day decitabine regimen, patient must be scheduled to receive one more cycle of 5 day decitabine.
- Recovered from all toxic effects of all prior therapy before entry into this study.
- Women of childbearing potential and all men must agree to practice a medically approved form of contraception (one of the following must be used: condoms [male or female] with a spermicidal agent, diaphragm or cervical cap with a spermicidal agent, intrauterine device, hormonal contraception, abstinence) during the course of the study and up to 2 months following the last dose of decitabine.
Exclusion Criteria:
- Candidates for up front high dose induction chemotherapy. MDS patients who are scheduled to receive decitabine prior to a bone marrow transplant or stem cell transplant are allowed.
- History of treatment failure with decitabine.
- Received any experimental agent within the preceding 30 days prior to screening.
- Uncontrolled cardiac or pulmonary disease.
- History of intestinal surgery, pancreatic surgery, or gastric surgery.
- Any clinically relevant disease, disorder (including psychiatric disorders), or condition, in the opinion of the Investigator, which may interfere with the objectives of the study, especially with the gastrointestinal (GI) absorption of the study drug, and/or with the safety of the subject in the study.
- Current active colitis of any etiology (Clostridium difficile colitis, ulcerative colitis, Crohn's disease, etc.) or a recent (less than 2 weeks) episode of colitis.
- Pregnant or lactating. Female patients of childbearing potential must have had a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to dosing.
- Known positive serology for human immunodeficiency virus (HIV).
- Active viral, fungal, or bacterial infection. No patient may enter the study unless infections have been fully treated.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
1
2
3
4
Arm Description
Outcomes
Primary Outcome Measures
Pharmacokinetic (PK) endpoints will be decitabine PK parameters: Tmax, Cmax, AUC0-inf, t1/2 and F.
Secondary Outcome Measures
Safety evaluations will include assessments of adverse events (AEs), medical history, physical examinations, vital signs measurements, use of concomitant medications, and laboratory assessments at baseline and throughout the study period.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00941109
Brief Title
Escalation Study to Determine Bioavailability of a Single Oral Dose of Decitabine in Patients With Myelodysplastic Syndrome (MDS)
Official Title
A Phase 1 Open-Label, Dose Escalation Study to Determine the Absolute Bioavailability of a Single Oral Dose Administration of Decitabine in Patients With Myelodysplastic Syndrome (MDS)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2016
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine how the body absorbs decitabine when taken orally in patients with Myelodysplastic Syndrome (MDS). Safety will also be assessed for this oral dose.
Detailed Description
Cohorts are dosed sequentially, and escalation may stop before the 5th cohort is dosed. Each cycle will be approximately 4 weeks in length. Following Cycle 1, patients may receive an additional 4 follow-up cycles of decitabine. Cycles 2-5 will include a 20 mg/m^2 1-hour IV infusion of decitabine on Days 1-5 for all cohorts.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome
Keywords
MDS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Arm Title
3
Arm Type
Experimental
Arm Title
4
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
Cohort 1: 30 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Intervention Type
Drug
Intervention Name(s)
decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
Cohort 2: 60 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Intervention Type
Drug
Intervention Name(s)
decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
Cohort 3: 120 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Intervention Type
Drug
Intervention Name(s)
decitabine
Other Intervention Name(s)
Dacogen
Intervention Description
Cohort 4: 240 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.
Primary Outcome Measure Information:
Title
Pharmacokinetic (PK) endpoints will be decitabine PK parameters: Tmax, Cmax, AUC0-inf, t1/2 and F.
Time Frame
Cycle 1 on Days 1 and 2 from predose up to 6 hours after administration.
Secondary Outcome Measure Information:
Title
Safety evaluations will include assessments of adverse events (AEs), medical history, physical examinations, vital signs measurements, use of concomitant medications, and laboratory assessments at baseline and throughout the study period.
Time Frame
Up to 30 days after the last dose of decitabine
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed de novo or secondary MDS.
Age greater than or equal to 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Adequate renal and hepatic function (creatinine less than or equal to 2.0 mg/dL, total bilirubin less than 2.0 mg/dL, aspartate aminotransferase [AST] or alanine aminotransferase [ALT] less than 3 times the upper limit of normal).
Life expectancy of at least 6 weeks.
If currently receiving 5 day decitabine regimen, patient must be scheduled to receive one more cycle of 5 day decitabine.
Recovered from all toxic effects of all prior therapy before entry into this study.
Women of childbearing potential and all men must agree to practice a medically approved form of contraception (one of the following must be used: condoms [male or female] with a spermicidal agent, diaphragm or cervical cap with a spermicidal agent, intrauterine device, hormonal contraception, abstinence) during the course of the study and up to 2 months following the last dose of decitabine.
Exclusion Criteria:
Candidates for up front high dose induction chemotherapy. MDS patients who are scheduled to receive decitabine prior to a bone marrow transplant or stem cell transplant are allowed.
History of treatment failure with decitabine.
Received any experimental agent within the preceding 30 days prior to screening.
Uncontrolled cardiac or pulmonary disease.
History of intestinal surgery, pancreatic surgery, or gastric surgery.
Any clinically relevant disease, disorder (including psychiatric disorders), or condition, in the opinion of the Investigator, which may interfere with the objectives of the study, especially with the gastrointestinal (GI) absorption of the study drug, and/or with the safety of the subject in the study.
Current active colitis of any etiology (Clostridium difficile colitis, ulcerative colitis, Crohn's disease, etc.) or a recent (less than 2 weeks) episode of colitis.
Pregnant or lactating. Female patients of childbearing potential must have had a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to dosing.
Known positive serology for human immunodeficiency virus (HIV).
Active viral, fungal, or bacterial infection. No patient may enter the study unless infections have been fully treated.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eisai US Medical Services
Organizational Affiliation
Eisai Inc.
Official's Role
Study Director
Facility Information:
City
Scottsdale
State/Province
Arizona
Country
United States
City
Denver
State/Province
Colorado
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
Bronx
State/Province
New York
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Tacoma
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Escalation Study to Determine Bioavailability of a Single Oral Dose of Decitabine in Patients With Myelodysplastic Syndrome (MDS)
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