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Trial record 1 of 1 for:    nct03502668
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Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS

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ClinicalTrials.gov Identifier: NCT03502668
Recruitment Status : Recruiting
First Posted : April 19, 2018
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: ASTX727 LD Drug: ASTX727 SD Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Multicenter, open label
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 27, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Decitabine

Arm Intervention/treatment
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 Name: 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 Name: 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 Name: oral decitabine (LD) + cedazuridine (E7727)

Drug: ASTX727 SD
oral decitabine (SD) + cedazuridine (E7727)
Other Name: oral decitabine (SD) + cedazuridine (E7727)




Primary Outcome Measures :
  1. Incidence of drug-related Grade ≥3 Adverse Events (AEs) or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule [ Time Frame: 18-24 months ]
    Phase 1: Safety

  2. Hematologic response based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence) [ Time Frame: 18-24 months ]
    Phase 2: Efficacy


Secondary Outcome Measures :
  1. %LINE-1 methylation change from baseline [ Time Frame: 18-24 months ]
    pharmacodynamics

  2. Area under the curve (AUC) [ Time Frame: 18-24 months ]
    pharmacokinetics parameter

  3. Maximum plasma concentration (Cmax) [ Time Frame: 18-24 months ]
    pharmacokinetics parameter

  4. Time to reach maximum concentration (Tmax) [ Time Frame: 18-24 months ]
    pharmacokinetics parameter

  5. Half life (t1/2) [ Time Frame: 18-24 months ]
    pharmacokinetics parameter

  6. 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 Frame: 18-24 months ]
    Phase 1: Efficacy

  7. Time to bone marrow blasts >5% [ Time Frame: 18-24 months ]
    Number of days from the date of randomization to the date when bone marrow blasts are >5% and increased by ≥50%.

  8. Leukemia-free survival [ Time Frame: 18-24 months ]
    Number of days from the date of randomization to the date when bone marrow or peripheral blood blasts reach ≥20%, or death from any cause

  9. Overall survival [ Time Frame: 18-24 months ]
    Number of days from the date of randomization to the date of death from any cause



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 RBCs or Hb of <8.5 g/dL in at least 2 blood counts prior to randomization.
    2. ANC of <0.5 × 10^9/L in at least 2 blood counts prior to randomization.
    3. 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. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03502668


Contacts
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Contact: Yuri Sano, MD, PhD 925-560-2844 yuri.sano@astx.com
Contact: Harold N Keer, MD, PhD 925-719-0741 harold.keer@astx.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Astex Pharmaceuticals, Inc.
Investigators
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Study Director: Yuri Sano, MD, PhD Astex Pharmaceuticals, Inc.
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Responsible Party: Astex Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03502668    
Other Study ID Numbers: ASTX727-03
First Posted: April 19, 2018    Key Record Dates
Last Update Posted: November 25, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astex Pharmaceuticals, Inc.:
low risk myelodysplastic syndromes, MDS, ASTX727
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors