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Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS

Trial Status: Active

Multicenter, open-label study of various ASTX727 LD doses and schedules to assess safety, pharmacodynamics, pharmacokinetics, and hematologic response in subjects with IPSS risk category of low-risk or Intermediate-1 MDS. This study will be conducted in two phases. In phase 1 subjects will be randomized into 3 cohorts in a 28-day cycles. Phase 2, 80 new subjects will be randomized in a 1:1 ratio into 2 doses / schedules.

Inclusion Criteria

  • Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.
  • Men or women ≥18 years with IPSS low risk or Int-1 MDS (all subjects). Subjects must have had at least 1 of the following disease-related criteria during the 8 weeks before randomization:
  • Red blood cell (RBC) transfusion dependence of 2 or more units of RBCs or Hb of <8.5 g/dL in at least 2 blood counts prior to randomization.
  • ANC of <0.5 × 10^9/L in at least 2 blood counts prior to randomization.
  • Platelet counts of <50 × 10^9/L in at least 2 blood counts prior to randomization.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Adequate organ function.
  • Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
  • Women of child-bearing potential must agree to use contraceptive measures of birth control for 6 months after completing treatment; men must use contraceptive measures and agree not to father a child for at least 3 months after completing treatment.

Exclusion Criteria

  • Treatment with any investigational drug or therapy within 2 weeks before study treatment.
  • Treatments for MDS must be concluded 1 month prior to study treatment.
  • Diagnosis of chronic myelomonocytic leukemia (CMML).
  • Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the subject has been disease free for at least 1 year.
  • Known active infection with human immunodeficiency virus or hepatitis viruses.

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: ACTIVE
Contact: Ravi Bhatia
Phone: 205-934-9591

California

Duarte
City of Hope Comprehensive Cancer Center
Status: APPROVED

Colorado

Aurora
University of Colorado Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Florida

Tampa
Moffitt Cancer Center
Status: ACTIVE

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: ACTIVE
Contact: Bobbie Ann Frye
Phone: 317-274-2992

Kansas

Fairway
University of Kansas Clinical Research Center
Status: ACTIVE
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: ACTIVE

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: ADMINISTRATIVELY_COMPLETE
Contact: Jay Yang
Phone: 313-516-8673

New York

Buffalo
Roswell Park Cancer Institute
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: IN_REVIEW

A Phase 1-2, multicenter, open-label study of various ASTX727 LD doses and schedules to assess the safety, pharmacodynamics (PD), pharmacokinetics (PK), and hematologic response in subjects with IPSS risk category of low-risk or Intermediate-1 MDS. The study will be conducted in 2 phases. Phase 1: In Stage A, subjects will be randomized into 3 cohorts of 6 subjects each testing different doses of oral decitabine with cedazuridine in 28-day cycles. When safety has been established in Phase 1 Stage A, Phase 1 Stage B will open, wherein additional 30 subjects will be randomized in a 1:1:1 ratio into 3 cohorts of 10 subjects. Phase 2: Using 2 doses/schedules one of which will be selected from Phase 1, 40 additional subjects per dose/schedule will be randomized in a 1:1 ratio. The selected doses/schedules will be evaluated for safety (drug-related AEs), efficacy (including hematologic response), PD (LINE-1 methylation, and fetal hemoglobin as fraction of total hemoglobin), and PK.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Astex Pharmaceuticals, Inc.

  • Primary ID ASTX727-03
  • Secondary IDs NCI-2018-01779
  • Clinicaltrials.gov ID NCT03502668