NCT03306264

Study of ASTX727 vs IV Decitabine in Participants With MDS, CMML, and AML

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), Chronic Myelomonocytic Leukemia (CMML), and Acute Myeloid Leukemia (AML)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 227 (actual)
• Sponsor: Astex Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Multicenter PK study of ASTX727 versus IV decitabine. Adult participants who were candidates to receive IV decitabine were randomized 1:1 to receive the ASTX727 tablet Daily×5 in Cycle 1 followed by IV decitabine 20 mg/m\^2 Daily×5 in Cycle 2, or the converse order. After completion of PK studies during the first 2 treatment cycles, participants continued to receive treatment with ASTX727 from Cycle 3 onward (in 28-day cycles) until disease progression, unacceptable toxicity, or the participants discontinued treatment or withdrew from the study.

Detailed description

This Phase 3 study established PK equivalence of ASTX727 to IV decitabine in approximately 227 evaluable participants. Eligible participants were randomized to receive both study treatments: oral investigational drug ASTX727, and IV decitabine, as follows: participants were 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, participants received the ASTX727 tablet Daily×5. Serial PK measurements (blood draws) were 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. Participants were 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, participants received a 1-hour infusion of IV decitabine 20 mg/m\^2 Daily×5. Serial PK measurements were done on Days 1 and 5, along with pre-dose and 1-hour post-infusion assessments on Day 3. In Cycles ≥3, participants received the ASTX727 tablet Daily×5 in 28-day cycles. (No PK assessments were done from Cycle 3 onward.)

Conditions

• Myelodysplastic Syndromes
• Chronic Myelomonocytic Leukemia
• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	ASTX727	ASTX727 oral tablet
DRUG	Dacogen	Decitabine 20 mg/m\^2 one-hour IV infusion

Timeline

• Start date: 2018-02-15
• Primary completion: 2021-09-10
• Completion: 2023-05-25
• First posted: 2017-10-11
• Last updated: 2024-08-27
• Results posted: 2024-07-01

Locations

84 sites across 10 countries: United States, Austria, Canada, Czechia, France, Germany, Hungary, Italy, Spain, United Kingdom

Regulatory

• FDA-regulated drug study