Escalation Study to Determine Bioavailability of a Single Oral Dose of Decitabine in Patients With Myelodysplastic Syndrome (MDS)

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)

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: decitabine; Drug: decitabine; Drug: decitabine; Drug: decitabine

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States
  • Colorado
    • Denver, Colorado, United States
  • Minnesota
    • Rochester, Minnesota, United States
  • New York
    • Bronx, New York, United States
  • Texas
    • Houston, Texas, United States
  • Washington
    • Tacoma, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed de novo or secondary MDS.
2. Age greater than or equal to 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
4. 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).
5. Life expectancy of at least 6 weeks.
6. If currently receiving 5 day decitabine regimen, patient must be scheduled to receive one more cycle of 5 day decitabine.
7. Recovered from all toxic effects of all prior therapy before entry into this study.
8. 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:

1. 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.
2. History of treatment failure with decitabine.
3. Received any experimental agent within the preceding 30 days prior to screening.
4. Uncontrolled cardiac or pulmonary disease.
5. History of intestinal surgery, pancreatic surgery, or gastric surgery.
6. 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.
7. 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.
8. 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.
9. Known positive serology for human immunodeficiency virus (HIV).
10. Active viral, fungal, or bacterial infection. No patient may enter the study unless infections have been fully treated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: decitabine; Cohort 1: 30 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 2: 60 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 3: 120 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 4: 240 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen
Experimental: 2	Drug: decitabine; Cohort 1: 30 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 2: 60 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 3: 120 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 4: 240 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen
Experimental: 3	Drug: decitabine; Cohort 1: 30 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 2: 60 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 3: 120 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 4: 240 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen
Experimental: 4	Drug: decitabine; Cohort 1: 30 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 2: 60 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 3: 120 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen; Drug: decitabine; Cohort 4: 240 mg oral on Day 1 and 20 mg/m^2 1-hour IV infusion on Days 2-5 of Cycle 1.; Other Names: Dacogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic (PK) endpoints will be decitabine PK parameters: Tmax, Cmax, AUC0-inf, t1/2 and F.	Cycle 1 on Days 1 and 2 from predose up to 6 hours after administration.

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	Up to 30 days after the last dose of decitabine

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Investigators: Study Director: Eisai US Medical Services, Eisai Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: July 15, 2009
• First Submitted That Met QC Criteria: July 16, 2009
• First Posted (Estimated): July 17, 2009

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: MDS
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: E7373-A001-101