Myelodysplastic SyndromesPhase 1NCT03813186
Effect of Food on Blood Levels of ASTX727
A Phase 1 study testing ASTX727 + Day 2 Food and ASTX727 + Day 4 Food in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Astex Pharmaceuticals, Inc. at 4 sites in United States.
Trial summary
This study is designed to examine blood levels of ASTX727, a fixed-dose combination tablet containing the combination of cedazuridine (100 mg) and decitabine (35 mg), when given under fed versus fasted conditions to participants with myelodysplastic syndromes (MDS), including refractory anemia with excess blasts in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Acute Myeloid Leukemia
- What is being tested?
- ASTX727 + Day 2 Food and ASTX727 + Day 4 Food
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesUnited States
- Study dates
- 8 Nov 2018to 16 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand and comply with the study procedures, including the ability to completely consume the breakfast meal in 20 minutes, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.
- Men or women ≥18 years with either:
- MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, CMML), and subjects with MDS IPSS int-1, -2, or high-risk MDS.
- AML, as diagnosed according to the 2016 WHO guidelines on acute leukemia, of any subtype except M3 (Acute Promyelocytic Leukemia), who are not candidates for intensive chemotherapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Adequate organ function defined as follows:
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- Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤5 × ULN.
- Renal: serum creatinine ≤1.5 × ULN or if serum creatinine is elevated; calculated creatinine clearance or glomerular filtration rate ≥50 mL/min.
- Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
- Subjects and their partners with reproductive potential must agree to use 2 highly effective contraceptive measures during the study and must agree not to become pregnant or father a child for 3 months after the last dose of study treatment.
Who cannot join
- Known or suspected hypersensitivity to decitabine, azacitidine, or cedazuridine.
- Treated with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment with investigational drug or therapy.
- Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
- Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of decitabine + cedazuridine or compromise the integrity of the study outcomes.
- Prior gastric surgery for ulcer disease, weight loss, etc., that would impair normal motility or absorption.
- Second malignancy currently requiring active chemotherapy. To clarify, patients with breast or prostate cancer stable on or responding to endocrine therapy, are eligible.
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- Known history of human immunodeficiency virus or if known seropositive for hepatitis C virus or hepatitis B virus.
- Active uncontrolled gastric or duodenal ulcer.
- Subjects with Acute Promyelocytic Leukemia.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Roswell Park
Buffalo, New York, 14263
Gabrail Cancer Center
Canton, Ohio, 44718
Vanderbilt
Nashville, Tennessee, 37232
Mays Cancer Center UT Health San Antonio MD Anderson Cancer Center
San Antonio, Texas, 78229
About this study
Official title: A Phase 1b Study to Evaluate the Effect of Food on Pharmacokinetics of ASTX727 (Cedazuridine and Decitabine) in Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia
This study is designed to examine blood levels of ASTX727, a fixed-dose combination tablet containing the combination of cedazuridine (100 mg) and decitabine (35 mg), when given under fed versus fasted conditions to participants with myelodysplastic syndromes (MDS), including refractory anemia with excess blasts in transformation or chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). This study will also assess the safety of ASTX727.
Read the detailed description
This is a Phase 1b, multicenter, open-label, randomized, two-sequence, crossover study of ASTX727 in participants with MDS, including refractory anemia with excess blasts in transformation or CMML, and AML. Participants will continue to be enrolled until evaluable data is collected from 12 participants. It is expected that approximately 18 participants will be enrolled in total.
This study will be conducted in 28-day cycles. All participants will take part in Cycle 1 and may continue into Cycles ≥2 at the investigator's discretion. Participants will receive one tablet of ASTX727 containing 100 mg cedazuridine and 35 mg decitabine once daily for 5 days in 28-day cycles starting from Cycle 1 Day 1.
Participants will be randomized in a 1:1 ratio to receive high-calorie, high-fat breakfast meal pre-dose on either Day 2 or Day 4 of Cycle 1. Blood will be drawn at specified time points in Cycle 1 on Days 2 through 5 to assess the effect of food on the PK of cedazuridine and decitabine.
After completion of the first treatment cycle, participants may continue to receive treatment with ASTX727 at the investigator's discretion for subsequent cycles (Days 1 through 5 of 28-day cycles), until disease progression, unacceptable toxicity, investigator decision to discontinue treatment, or the participant decides to discontinue treatment or withdraw from the study. In Cycles ≥2, participants will fast for 2 hours before and 2 hours after taking the ASTX727 tablet on all dosing days.
- Being tested
- ASTX727 + Day 2 Food, ASTX727 + Day 4 Food
- Keywords
- MDS, CMML, ASTX727, decitabine, AML
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX727 + Day 2 FoodDrug
Also called cedazuridine + decitabine + food on Day 2
ASTX727 is an oral drug product composed of a fixed-dose combination of cedazuridine (E7727), a CDA inhibitor, and decitabine. Food is a high-calorie, high-fat breakfast meal of 800-1000 calories given on Day 2.
ASTX727 + Day 4 FoodDrug
Also called cedazuridine + decitabine + food on Day 4
ASTX727 is an oral drug product composed of a fixed-dose combination of cedazuridine (E7727), a CDA inhibitor, and decitabine. Food is a high-calorie, high-fat breakfast meal of 800-1000 calories given on Day 4.
| Study group | Role | What they receive |
|---|---|---|
| ASTX727 + Day 2 Food | Experimental | Subjects will receive ASTX727 on Days 1-5 of Cycle 1 and a high-calorie, high-fat breakfast meal of 800-1000 calories pre-dose on Day 2 of Cycle 1. Receives: Drug: ASTX727 + Day 2 Food |
| ASTX727 + Day 4 Food | Experimental | Subjects will receive ASTX727 on Days 1-5 of Cycle 1 and a high-calorie, high-fat breakfast meal of 800-1000 calories pre-dose on Day 4 of Cycle 1. Receives: Drug: ASTX727 + Day 4 Food |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC0-t (area under the concentration-time curve from time 0 to t hours).
Area under the concentration-time curve from time 0 to t hours.
Measured: 6 months
AUC0-8 (area under the concentration-time curve from time 0 to 8 hours).
Area under the concentration-time curve from time 0 to 8 hours.
Measured: 6 months
AUC0-24 (area under the concentration-time curve from time 0 to 24 hours).
Area under the concentration-time curve from time 0 to 24 hours
Measured: 6 months
AUC0-inf (area under the concentration-time curve from time 0 to infinity).
Area under the concentration-time curve from time 0 to infinity.
Measured: 6 months
Cmax (maximum plasma concentration).
Maximum plasma concentration.
Measured: 6 months
Secondary outcomes (5)
hemoglobin level
Assessed in g/dL
Measured: 6 months
platelet count
Assessed as 10^9/L
Measured: 6 months
white blood cell count
Assessed as fraction of 1
Measured: 6 months
neutrophils
Assessed as percent
Measured: 6 months
Subject-reported and investigator-observed incidence and severity of adverse events.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2019
- Study start8 Nov 2018
- Primary completion14 Jun 2019
- Study completion16 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astex Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03813186
- Sponsor's protocol ID
- ASTX727-04
- Status last verified
- Aug 2024
- First submitted
- 11 Jan 2019
- Last updated
- 2 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.
PubMed 16609072
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study to Evaluate the Effect of Food on Pharmacokinetics of ASTX727 (Cedazuridine and Decitabine) in Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03813186
- Acronym / sponsor ID
- ASTX727-04
- Keywords
- MDS, CMML, ASTX727, decitabine, AML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Astex Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Nov 2018 (actual)
- Primary completion
- 14 Jun 2019 (actual)
- Study completion
- 16 Dec 2019 (actual)
- First posted
- 23 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to examine blood levels of ASTX727, a fixed-dose combination tablet containing the combination of cedazuridine (100 mg) and decitabine (35 mg), when given under fed versus fasted conditions to participants with myelodysplastic syndromes (MDS), including refractory anemia with excess blasts in transformation or chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). This study will also assess the safety of ASTX727.
Detailed description
This is a Phase 1b, multicenter, open-label, randomized, two-sequence, crossover study of ASTX727 in participants with MDS, including refractory anemia with excess blasts in transformation or CMML, and AML. Participants will continue to be enrolled until evaluable data is collected from 12 participants. It is expected that approximately 18 participants will be enrolled in total.
This study will be conducted in 28-day cycles. All participants will take part in Cycle 1 and may continue into Cycles ≥2 at the investigator's discretion. Participants will receive one tablet of ASTX727 containing 100 mg cedazuridine and 35 mg decitabine once daily for 5 days in 28-day cycles starting from Cycle 1 Day 1.
Participants will be randomized in a 1:1 ratio to receive high-calorie, high-fat breakfast meal pre-dose on either Day 2 or Day 4 of Cycle 1. Blood will be drawn at specified time points in Cycle 1 on Days 2 through 5 to assess the effect of food on the PK of cedazuridine and decitabine.
After completion of the first treatment cycle, participants may continue to receive treatment with ASTX727 at the investigator's discretion for subsequent cycles (Days 1 through 5 of 28-day cycles), until disease progression, unacceptable toxicity, investigator decision to discontinue treatment, or the participant decides to discontinue treatment or withdraw from the study. In Cycles ≥2, participants will fast for 2 hours before and 2 hours after taking the ASTX727 tablet on all dosing days.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ASTX727 + Day 2 Food | Experimental | Drug: ASTX727 + Day 2 FoodSubjects will receive ASTX727 on Days 1-5 of Cycle 1 and a high-calorie, high-fat breakfast meal of 800-1000 calories pre-dose on Day 2 of Cycle 1. |
| ASTX727 + Day 4 Food | Experimental | Drug: ASTX727 + Day 4 FoodSubjects will receive ASTX727 on Days 1-5 of Cycle 1 and a high-calorie, high-fat breakfast meal of 800-1000 calories pre-dose on Day 4 of Cycle 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Able to understand and comply with the study procedures, including the ability to completely consume the breakfast meal in 20 minutes, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.
- Men or women ≥18 years with either:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Adequate organ function defined as follows:
- Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
Key exclusion criteria (9 listed)
- Known or suspected hypersensitivity to decitabine, azacitidine, or cedazuridine.
- Treated with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment with investigational drug or therapy.
- Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
- Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of decitabine + cedazuridine or compromise the integrity of the study outcomes.
- Prior gastric surgery for ulcer disease, weight loss, etc., that would impair normal motility or absorption.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASTX727 + Day 2 FoodAlso: cedazuridine + decitabine + food on Day 2ASTX727 is an oral drug product composed of a fixed-dose combination of cedazuridine (E7727), a CDA inhibitor, and decitabine. Food is a high-calorie, high-fat breakfast meal of 800-1000 calories given on Day 2. | Drug | ASTX727 + Day 2 Food |
| ASTX727 + Day 4 FoodAlso: cedazuridine + decitabine + food on Day 4ASTX727 is an oral drug product composed of a fixed-dose combination of cedazuridine (E7727), a CDA inhibitor, and decitabine. Food is a high-calorie, high-fat breakfast meal of 800-1000 calories given on Day 4. | Drug | ASTX727 + Day 4 Food |
Primary outcome
AUC0-t (area under the concentration-time curve from time 0 to t hours).
Time frame: 6 months
Area under the concentration-time curve from time 0 to t hours.
AUC0-8 (area under the concentration-time curve from time 0 to 8 hours).
Time frame: 6 months
Area under the concentration-time curve from time 0 to 8 hours.
AUC0-24 (area under the concentration-time curve from time 0 to 24 hours).
Time frame: 6 months
Area under the concentration-time curve from time 0 to 24 hours
AUC0-inf (area under the concentration-time curve from time 0 to infinity).
Time frame: 6 months
Area under the concentration-time curve from time 0 to infinity.
Cmax (maximum plasma concentration).
Time frame: 6 months
Maximum plasma concentration.
5 secondary outcomes
hemoglobin level
Time frame: 6 months
platelet count
Time frame: 6 months
white blood cell count
Time frame: 6 months
neutrophils
Time frame: 6 months
Subject-reported and investigator-observed incidence and severity of adverse events.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2024.
- Background: PubMed 16609072Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASTX727 + Day 2 Food and ASTX727 + Day 4 Food in people with Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia, run by Astex Pharmaceuticals, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC0-t (area under the concentration-time curve from time 0 to t hours). (time frame: 6 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03813186, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2024.