Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS)

Last updated: July 31, 2024
Sponsor: Astex Pharmaceuticals, Inc.
Overall Status: Completed

Phase

1/2

Condition

Leukemia

Myelodysplastic Syndromes (Mds)

Platelet Disorders

Treatment

ASTX727 Dose Escalation

ASTX727 Fixed-Dose Combination

ASTX727 Dose Confirmation

Clinical Study ID

NCT02103478
ASTX727-01
  • Ages > 18
  • All Genders

Study Summary

This first-in-human, 3-stage, open-label study evaluated the safety and pharmacokinetics of ASTX727, as well as determined the dose for later stages.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • International Prognostic Scoring System (IPSS) low, intermediate -1, intermediate-2,or high risk MDS (including chronic myelomonocytic leukemia; CMML) in DoseEscalation and Dose Confirmation-Randomization; only intermediate-2, or high riskMDS in Dose Confirmation-Open Label

  • 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

Exclusion Criteria:

  • Previous treatment with 2 or more courses of decitabine (all stages) or azacitidine (Dose Confirmation stage only)

  • 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

Study Design

Total Participants: 130
Treatment Group(s): 3
Primary Treatment: ASTX727 Dose Escalation
Phase: 1/2
Study Start date:
October 28, 2014
Estimated Completion Date:
December 04, 2019

Study Description

The trial was designed to define daily doses of the individual components (cedazuridine [E7727] or decitabine) so that decitabine exposure after oral administration would be comparable to exposure after IV decitabine at the approved daily dose of 20 mg/m^2. The main objective of Phases 1 and 2 was to establish and confirm the doses of the 2 components to be used in the final fixed-dose combination (FDC) product (ASTX727) using mainly pharmacokinetics and pharmacodynamics as endpoints.

Connect with a study center

  • University of Alberta Hospital

    Edmonton, Alberta T6G 2G3
    Canada

    Site Not Available

  • Princess Margaret Cancer Center

    Toronto, Ontario M5G 2M9
    Canada

    Site Not Available

  • Sunnybrook Health Sciences Centre, Odette Cancer Centre

    Toronto, Ontario M4N 3M5
    Canada

    Site Not Available

  • Hôpital Maisonneuve-Rosemont

    Montréal, Quebec H1T 2M4
    Canada

    Site Not Available

  • Mayo Clinic

    Phoenix, Arizona 85054
    United States

    Site Not Available

  • Mayo Clinic

    Scottsdale, Arizona 85259
    United States

    Site Not Available

  • University of Southern California

    Los Angeles, California 90024
    United States

    Site Not Available

  • University of Chicago

    Chicago, Illinois 60637
    United States

    Site Not Available

  • Horizon Oncology

    Lafayette, Indiana 47905
    United States

    Site Not Available

  • Johns Hopkins

    Baltimore, Maryland 21231
    United States

    Site Not Available

  • Dana Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Site Not Available

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Site Not Available

  • John Theurer Cancer Center/ Hackensack University Medical Center

    Hackensack, New Jersey 07601
    United States

    Site Not Available

  • Roswell Park Cancer Institute

    Buffalo, New York 14263
    United States

    Site Not Available

  • Weill Cornell Medical College - New York Presbyterian Hospital

    New York, New York 10021
    United States

    Site Not Available

  • Vanderbilt Ingram Cancer Center

    Nashville, Tennessee 37232
    United States

    Site Not Available

  • M. D. Anderson

    Houston, Texas 77030
    United States

    Site Not Available

  • Medical College of Wisconsin

    Milwaukee, Wisconsin 53226
    United States

    Site Not Available

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