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

Official Title

A Randomized, Open-Label, Phase 1-2 Study of ASTX727 Low Dose (ASTX727 LD) Extended Schedule in Subjects With Lower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS)

Summary:

Multicenter, open-label study of various ASTX727 LD doses and schedules to assess safety, pharmacodynamics, pharmacokinetics, and hematologic response in subjects with International Prognostic Scoring System (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.

Trial Description

Primary Outcome:

  • Incidence of drug-related Grade ≥3 Adverse Events (AEs) or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule
  • Hematologic response based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Secondary Outcome:
  • %LINE-1 methylation change from baseline
  • Area under the curve (AUC)
  • Maximum plasma concentration (Cmax)
  • Time to reach maximum concentration (Tmax)
  • Half life (t1/2)
  • Hematologic response (Phase 1 only) based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
  • Time to bone marrow blasts >5%
  • Leukemia-free survival
  • Overall survival

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 (long interspersed nucleotide element-1 (LINE-1 methylation, and fetal hemoglobin as fraction of total hemoglobin), and PK.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society