Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS)
NCT ID: NCT02103478
Last Updated: 2024-08-27
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
130 participants
INTERVENTIONAL
2014-10-28
2019-12-04
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Phase 1 Dose Escalation
Starting cohort was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m\^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
ASTX727 Dose Escalation
Oral investigational product and approved IV decitabine
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (E7727) (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m\^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
ASTX727 Dose Confirmation
Randomization cross over design for courses 1 and 2
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine (E7727)/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m\^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
ASTX727 Fixed-Dose Combination
Fixed-dose investigational product
Interventions
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ASTX727 Dose Escalation
Oral investigational product and approved IV decitabine
ASTX727 Dose Confirmation
Randomization cross over design for courses 1 and 2
ASTX727 Fixed-Dose Combination
Fixed-dose investigational product
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Eastern Cooperative Oncology Group (ECOG) 0 to 2
* No major surgery within 2 weeks of starting study treatment
* No cytotoxic chemotherapy within 2 weeks of starting study treatment
* Able to swallow pills
Exclusion Criteria
* Treatment with investigational therapy within 2 weeks of study treatment
* Uncontrolled medical disease(s) or active, uncontrolled infection
* Diagnosed with acute myeloid leukemia (AML)
* Active uncontrolled gastric or duodenal ulcer
* Known history of HIV or hepatitis C or B
18 Years
ALL
No
Sponsors
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Astex Pharmaceuticals, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Mohammad Azab, MD
Role: STUDY_DIRECTOR
Astex Pharmaceuticals, Inc.
James Lowder, MD
Role: STUDY_CHAIR
Astex Pharmaceuticals, Inc.
Locations
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Mayo Clinic
Phoenix, Arizona, United States
University of Southern California
Los Angeles, California, United States
University of Chicago
Chicago, Illinois, United States
Horizon Oncology
Lafayette, Indiana, United States
Johns Hopkins
Baltimore, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
John Theurer Cancer Center/ Hackensack University Medical Center
Hackensack, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, United States
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States
M. D. Anderson
Houston, Texas, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
University of Alberta Hospital
Edmonton, Alberta, Canada
Sunnybrook Health Sciences Centre, Odette Cancer Centre
Toronto, Ontario, Canada
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Hôpital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Countries
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References
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Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, Odenike O, DeZern AE, Yee K, Busque L, O'Connell C, Michaelis LC, Brandwein J, Kantarjian H, Oganesian A, Azab M, Savona MR. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020 Aug 6;136(6):674-683. doi: 10.1182/blood.2019004143.
Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, Faderl S, Harb W, Kantarjian H, Lowder J, Oganesian A, Azab M, Garcia-Manero G. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol. 2019 Apr;6(4):e194-e203. doi: 10.1016/S2352-3026(19)30030-4.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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ASTX727-01
Identifier Type: -
Identifier Source: org_study_id
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