Study of ASTX727 vs IV Decitabine in MDS and CMML
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|ClinicalTrials.gov Identifier: NCT03306264|
Recruitment Status : Recruiting
First Posted : October 11, 2017
Last Update Posted : November 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia||Drug: ASTX727 Drug: Dacogen||Phase 3|
This Phase 3 study will establish PK equivalence of ASTX727 to IV decitabine in approximately 118 evaluable subjects. Eligible subjects will receive both study treatments: oral investigational drug ASTX727, and IV decitabine, as follows: subjects will be randomly assigned 1:1 to receive ASTX727 or IV decitabine in Cycle 1 and then cross over to the other therapy in Cycle 2.
In the ASTX727 cycle, subjects will receive the ASTX727 tablet Daily×5. Serial PK measurements (blood draws) will be done on Days 1, 2, and 5, along with pre-dose PK assessments on Days 1-5 and an assessment at 3 hours post dose on Day 3. Subjects will be required to fast from food for 4 hours on days when receiving ASTX727: at least 2 hours before and 2 hours after dosing.
In the IV decitabine cycle, subjects will receive a 1-hour infusion of IV decitabine 20 mg/m^2 Daily×5. Serial PK measurements will be done on Days 1 and 5, along with pre-dose and 1-hour post-infusion assessments on Day 3.
In Cycles ≥3, subjects will receive the ASTX727 tablet Daily×5 in 28-day cycles. (No PK assessments will be done from Cycle 3 onward.)
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||132 participants|
|Intervention Model:||Crossover Assignment|
|Intervention Model Description:||Multicenter, randomized, open-label, 2-period, 2-sequence crossover study|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3, Randomized, Open-Label, Crossover Study of ASTX727 (Cedazuridine and Decitabine Fixed-Dose Combination) Versus IV Decitabine in Subjects With Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) [ASTX727-02]|
|Actual Study Start Date :||February 15, 2018|
|Estimated Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||June 30, 2019|
ASTX727 (cedazuridine + decitabine) - Cycle 1 or Cycle 2 (crossover)
ASTX727 is a tablet for oral administration, containing the fixed-dose combination of 100 mg cedazuridine (a cytidine deaminase inhibitor) and 35 mg decitabine, given by mouth Dailyx5 in 28-day cycles (in Cycle 1 or Cycle 2, then in Cycle 3 and beyond).
Other Name: cedazuridine + decitabine
Active Comparator: IV decitabine
Dacogen (decitabine for injection) - Cycle 1 or Cycle 2 (crossover)
Decitabine 20 mg/m^2 one-hour IV infusion Dailyx5 (in one 28-day cycle: either Cycle 1 or Cycle 2).
Other Name: decitabine for injection
- Total 5-day Area Under the Curve (AUC) exposures of decitabine [ Time Frame: 18 months ]Primary Endpoint
- Numbers of subjects with adverse events (AEs); the severity (intensity) of AEs will be graded according to CTCAE v4.03. [ Time Frame: 18 months ]Safety assessment
- Long Interspersed Nucleotide Elements (LINE)-1 demethylation [ Time Frame: 18 months ]Pharmacodynamics assessment
- Maximum plasma concentration (Cmax) [ Time Frame: 2 months ]Secondary pharmacokinetics parameter
- Time to reach maximum concentration (Tmax) [ Time Frame: 2 months ]Secondary pharmacokinetics parameter
- Elimination rate constant [ Time Frame: 2 months ]Secondary pharmacokinetics parameter
- Apparent total systemic clearance [ Time Frame: 2 months ]Secondary pharmacokinetics parameter
- Apparent elimination half life [ Time Frame: 2 months ]Secondary pharmacokinetics parameter
- Apparent volume of distribution [ Time Frame: 2 months ]Secondary pharmacokinetics parameter
- Complete response (CR), marrow CR, partial response; hematologic improvement based on International Working Group 2006 MDS response criteria. [ Time Frame: 18 months ]Efficacy analysis - Clinical response
- Red blood cell (RBC) transfusion independence: defined as no RBC transfusion for 56 consecutive days. [ Time Frame: 18 months ]Efficacy analysis - RBC transfusion independence
- Platelet transfusion independence: defined as no platelet transfusion for 8 consecutive weeks. [ Time Frame: 18 months ]Efficacy analysis - Platelet transfusion independence
- Leukemia-free survival: number of days from date of randomization to date when bone marrow or peripheral blood blasts reach ≥20%, or death. [ Time Frame: 18 months ]Efficacy analysis - Leukemia-free survival
- Overall survival: number of days from date subject was randomized to date of death. [ Time Frame: 18 months ]Efficacy analysis - Overall survival
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): NCT03306264
|Contact: James N Lowder, MDfirstname.lastname@example.org|
|Contact: Harold Keer, MD, PhDemail@example.com|
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|Study Director:||James N Lowder, MD||Astex Pharmaceuticals|