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

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Astex Pharmaceuticals

Status and phase

Active, not recruiting
Phase 2
Phase 1

Conditions

Myelodysplastic Syndromes

Treatments

Drug: ASTX727 LD
Drug: ASTX727 SD

Study type

Interventional

Funder types

Industry

Identifiers

NCT03502668
ASTX727-03

Details and patient eligibility

About

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.

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

Enrollment

160 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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:

    1. Red blood cell (RBC) transfusion dependence of 2 or more units of RBC transfusions (RBC transfusion administered for hemoglobin (Hb) levels ≤9.0 g/dL are counted).
    2. Hb of <9.0 g/dL in at least 2 blood counts prior to randomization or in 1 blood count if RBC transfusion was received.
    3. Absolute Neutrophil Count (ANC) of <0.5 × 10^9/L in at least 2 blood counts prior to randomization.
    4. Platelet counts of <50 × 10^9/L in at least 2 blood counts prior to randomization.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

  4. Adequate organ function.

  5. 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.

  6. 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. Prior treatment with azacitidine, decitabine, or guadecitabine.
  4. Diagnosis of chronic myelomonocytic leukemia (CMML).
  5. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
  6. 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.
  7. Known active infection with human immunodeficiency virus or hepatitis viruses.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

160 participants in 3 patient groups

Phase 1 Stage A
Experimental group
Description:
3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD
Treatment:
Drug: ASTX727 LD
Phase 1 Stage B
Experimental group
Description:
3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD
Treatment:
Drug: ASTX727 LD
Phase 2
Experimental group
Description:
80 additional subjects randomized in a 1:1 ratio studying two different doses
Treatment:
Drug: ASTX727 SD
Drug: ASTX727 LD

Trial contacts and locations

29

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Data sourced from clinicaltrials.gov

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