Description:
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.
Title
- Brief Title: Effect of Food on Blood Levels of ASTX727
- 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
Clinical Trial IDs
- ORG STUDY ID:
ASTX727-04
- NCT ID:
NCT03813186
Conditions
- Myelodysplastic Syndromes
- Chronic Myelomonocytic Leukemia
- Acute Myeloid Leukemia
Interventions
Drug | Synonyms | Arms |
---|
ASTX727 + Day 2 Food | cedazuridine + decitabine + food on Day 2 | ASTX727 + Day 2 Food |
ASTX727 + Day 4 Food | cedazuridine + decitabine + food on Day 4 | ASTX727 + Day 4 Food |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | |
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. | |
Eligibility Criteria
Inclusion Criteria:
1. 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.
2. Men or women ≥18 years with either:
1. 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.
2. 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
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4. Adequate organ function defined as follows:
1. 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.
2. Renal: serum creatinine ≤1.5 × ULN or if serum creatinine is elevated; calculated
creatinine clearance or glomerular filtration rate ≥50 mL/min.
5. 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.
6. 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.
Exclusion Criteria:
1. Known or suspected hypersensitivity to decitabine, azacitidine, or cedazuridine.
2. 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.
3. Poor medical risk because of other conditions such as uncontrolled systemic diseases
or active uncontrolled infections.
4. 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.
5. Prior gastric surgery for ulcer disease, weight loss, etc., that would impair normal
motility or absorption.
6. Second malignancy currently requiring active chemotherapy. To clarify, patients with
breast or prostate cancer stable on or responding to endocrine therapy, are eligible.
7. Known history of human immunodeficiency virus or if known seropositive for hepatitis C
virus or hepatitis B virus.
8. Active uncontrolled gastric or duodenal ulcer.
9. Subjects with Acute Promyelocytic Leukemia.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | AUC0-t (area under the concentration-time curve from time 0 to t hours). |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Area under the concentration-time curve from time 0 to t hours. |
Secondary Outcome Measures
Measure: | hemoglobin level |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Assessed in g/dL |
Measure: | platelet count |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Assessed as 10^9/L |
Measure: | white blood cell count |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Assessed as fraction of 1 |
Measure: | neutrophils |
Time Frame: | 6 months |
Safety Issue: | |
Description: | Assessed as percent |
Measure: | Subject-reported and investigator-observed incidence and severity of adverse events. |
Time Frame: | 6 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Astex Pharmaceuticals, Inc. |
Trial Keywords
- MDS
- CMML
- ASTX727
- decitabine
- AML
Last Updated
February 18, 2020