Back to resultsPhase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS
Primary Purpose
Myelodysplastic Syndromes
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ASTX727 LD
ASTX727 SD
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring low risk myelodysplastic syndromes, MDS, ASTX727
Eligibility Criteria
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:
- 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).
- 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.
- Absolute Neutrophil Count (ANC) of <0.5 × 10^9/L in at least 2 blood counts prior to randomization.
- Platelet counts of <50 × 10^9/L in at least 2 blood counts prior to randomization.
- 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.
- Prior treatment with azacitidine, decitabine, or guadecitabine.
- 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.
Sites / Locations
- The University of Alabama at Birmingham
- University of Colorado, Anschutz Cancer Pavilion
- Yale Cancer Center
- Mayo Clinic Florida
- BRCR Medical Center Inc.
- Moffitt Cancer Center Site#507
- The University of Chicago
- Indiana University Health Hospital - Simon Cancer Center
- University of Kansas Clinical Research Center
- The Center for Cancer and Blood Disorders (RCCA MD LLC - Maryland Division)
- Mayo Clinic
- University of Nebraska Medical Center
- Roswell Park Comprehensive Cancer Center
- Oregon Health and Science University Knight Cancer Institute
- Sarah Cannon Research Institute
- Vanderbilt University Medical Center - Hematology-Oncology
- The University of Texas MD Anderson Cancer Center
- Texas Oncology - Tyler
- ZNA - Campus Middelheim
- Az St-Jan Brugge-Oostende A.V.
- London Regional Cancer Center
- University of Alberta Hospital - Hematology Research
- Universitaetsklinikum Freiburg Site#703
- Universitätsklinikum Halle
- Universita degli Studi di Firenze
- Hospital Universitario Vall d Hebron
- Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol
- Hospital General Universitario Gregorio Marañón
- Hospital Univeristario y Politecnico La Fe Servicio de Hematologia
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Phase 1 Stage A
Phase 1 Stage B
Phase 2
Arm Description
3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD
3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD
80 additional subjects randomized in a 1:1 ratio studying two different doses
Outcomes
Primary Outcome Measures
Incidence of drug-related Grade ≥3 Adverse Events (AEs) or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule
Phase 1: Safety
Hematologic response based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Phase 2: Efficacy
Secondary Outcome Measures
%LINE-1 methylation change from baseline
pharmacodynamics
Area under the curve (AUC)
pharmacokinetics parameter
Maximum plasma concentration (Cmax)
pharmacokinetics parameter
Time to reach maximum concentration (Tmax)
pharmacokinetics parameter
Half life (t1/2)
pharmacokinetics parameter
Hematologic response (Phase 1 only) based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Phase 1: Efficacy
Time to bone marrow blasts >5%
Number of days from the date of randomization to the date when bone marrow blasts are >5% and increased by ≥50%.
Leukemia-free survival
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
Overall survival
Number of days from the date of randomization to the date of death from any cause
Full Information
NCT ID
NCT03502668
First Posted
April 11, 2018
Last Updated
September 29, 2023
Sponsor
Astex Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03502668
Brief Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 27, 2018 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astex Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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 (long interspersed nucleotide element-1 (LINE-1 methylation, and fetal hemoglobin as fraction of total hemoglobin), and PK.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes
Keywords
low risk myelodysplastic syndromes, MDS, ASTX727
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Multicenter, open label
Masking
None (Open Label)
Allocation
Randomized
Enrollment
160 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 Stage A
Arm Type
Experimental
Arm Description
3 cohorts of 6 subjects each in a schedule in 28-day cycles of ASTX727 LD
Arm Title
Phase 1 Stage B
Arm Type
Experimental
Arm Description
3 cohorts of 10 subjects each in 28-day cycles of ASTX727 LD
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
80 additional subjects randomized in a 1:1 ratio studying two different doses
Intervention Type
Drug
Intervention Name(s)
ASTX727 LD
Other Intervention Name(s)
oral decitabine (LD) + cedazuridine (E7727)
Intervention Description
oral decitabine (LD) + cedazuridine (E7727)
Intervention Type
Drug
Intervention Name(s)
ASTX727 SD
Other Intervention Name(s)
oral decitabine (SD) + cedazuridine (E7727)
Intervention Description
oral decitabine (SD) + cedazuridine (E7727)
Primary Outcome Measure Information:
Title
Incidence of drug-related Grade ≥3 Adverse Events (AEs) or dose-limiting toxicities (DLTs) (if any) for each cohort dose/schedule
Description
Phase 1: Safety
Time Frame
18-24 months
Title
Hematologic response based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Description
Phase 2: Efficacy
Time Frame
18-24 months
Secondary Outcome Measure Information:
Title
%LINE-1 methylation change from baseline
Description
pharmacodynamics
Time Frame
18-24 months
Title
Area under the curve (AUC)
Description
pharmacokinetics parameter
Time Frame
18-24 months
Title
Maximum plasma concentration (Cmax)
Description
pharmacokinetics parameter
Time Frame
18-24 months
Title
Time to reach maximum concentration (Tmax)
Description
pharmacokinetics parameter
Time Frame
18-24 months
Title
Half life (t1/2)
Description
pharmacokinetics parameter
Time Frame
18-24 months
Title
Hematologic response (Phase 1 only) based on normalization of conversion of any baseline cytopenia or anemia (hemoglobin response, neutrophil response, platelet response, transfusion independence)
Description
Phase 1: Efficacy
Time Frame
18-24 months
Title
Time to bone marrow blasts >5%
Description
Number of days from the date of randomization to the date when bone marrow blasts are >5% and increased by ≥50%.
Time Frame
18-24 months
Title
Leukemia-free survival
Description
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
Time Frame
18-24 months
Title
Overall survival
Description
Number of days from the date of randomization to the date of death from any cause
Time Frame
18-24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
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).
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.
Absolute Neutrophil Count (ANC) of <0.5 × 10^9/L in at least 2 blood counts prior to randomization.
Platelet counts of <50 × 10^9/L in at least 2 blood counts prior to randomization.
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.
Prior treatment with azacitidine, decitabine, or guadecitabine.
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.
Facility Information:
Facility Name
The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
University of Colorado, Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Mayo Clinic Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
BRCR Medical Center Inc.
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Facility Name
Moffitt Cancer Center Site#507
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
The University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University Health Hospital - Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Clinical Research Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
The Center for Cancer and Blood Disorders (RCCA MD LLC - Maryland Division)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Oregon Health and Science University Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt University Medical Center - Hematology-Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
ZNA - Campus Middelheim
City
Antwerp
Country
Belgium
Facility Name
Az St-Jan Brugge-Oostende A.V.
City
Brugge
Country
Belgium
Facility Name
London Regional Cancer Center
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
University of Alberta Hospital - Hematology Research
City
Edmonton
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Universitaetsklinikum Freiburg Site#703
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitätsklinikum Halle
City
Halle
ZIP/Postal Code
06120
Country
Germany
Facility Name
Universita degli Studi di Firenze
City
Firenze
Country
Italy
Facility Name
Hospital Universitario Vall d Hebron
City
Barcelona
Country
Spain
Facility Name
Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol
City
Barcelona
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañón
City
Madrid
Country
Spain
Facility Name
Hospital Univeristario y Politecnico La Fe Servicio de Hematologia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase 1-2 Study of Low Dose ASTX727 (ASTX727 LD) in Lower Risk MDS
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