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Clinical Trial 19939

Cancer Type: Malignant Hematology
Interventions:

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • David Sallman

Call 813-745-6100
or 1-800-679-0775
Overview

Study 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 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.

Objective

Study Objectives: Phase 1 Primary Objectives: To assess the safety profile of doses and schedules of ASTX727 LD. To select the ASTX727 LD dose(s) and schedule(s) to study in Phase 2. Secondary Objectives: To assess the pharmacodynamic (PD) activity of doses and schedules of ASTX727 LD. To characterize the pharmacokinetics (PK) of decitabine, cedazuridine, and its metabolite cedazuridine-epimer. To assess hematologic response. Phase 2 Primary Objective: To assess the clinical efficacy of the doses and schedules selected from Phase 1. Secondary Objectives: To assess the safety of the selected ASTX727 LD doses and schedules. To assess PD activity and PK of decitabine at the selected ASTX727 LD doses and 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: (a) Red blood cell (RBC) transfusion dependence of 2 or more units of RBCs or Hb of > 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