Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. 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.
  2. 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:
  3. 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.
  4. ANC of <0.5 × 10^9/L in at least 2 blood counts prior to randomization.
  5. Platelet counts of <50 × 10^9/L in at least 2 blood counts prior to randomization.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  7. Adequate organ function.
  8. 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.
  9. 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

  1. Treatment with any investigational drug or therapy within 2 weeks before study treatment.
  2. Treatments for MDS must be concluded 1 month prior to study treatment.
  3. Diagnosis of chronic myelomonocytic leukemia (CMML).
  4. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
  5. 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.
  6. Known active infection with human immunodeficiency virus or hepatitis viruses.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Multicenter, open label
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1 Stage A
3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD
  • Drug: ASTX727 LD
    oral decitabine (LD) + cedazuridine (E7727)
    Other names:
    • oral decitabine (LD) + cedazuridine (E7727)
Experimental
Phase 1 Stage B
3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD
  • Drug: ASTX727 LD
    oral decitabine (LD) + cedazuridine (E7727)
    Other names:
    • oral decitabine (LD) + cedazuridine (E7727)
Experimental
Phase 2
80 additional subjects randomized in a 1:1 ratio studying two different doses
  • Drug: ASTX727 LD
    oral decitabine (LD) + cedazuridine (E7727)
    Other names:
    • oral decitabine (LD) + cedazuridine (E7727)
  • Drug: ASTX727 SD
    oral decitabine (SD) + cedazuridine (E7727)
    Other names:
    • oral decitabine (SD) + cedazuridine (E7727)

Recruiting Locations

The University of Alabama at Birmingham
Birmingham, Alabama 35233
Contact:
Nandika S Nagodawithana, MBBS, MSc, MD, MSHI
205-934-6624
nandika@uab.edu

More Details

NCT ID
NCT03502668
Status
Recruiting
Sponsor
Astex Pharmaceuticals, Inc.

Study Contact

Yuri Sano, MD, PhD
925-560-2844
yuri.sano@astx.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.