PK/Efficacy Bridging Study of ASTX727 in Chinese Subjects With Myelodysplastic Syndromes

Myelodysplastic Syndromes Clinical Trial

Official title:

An Open-label, Crossover, Pharmacokinetic and Efficacy Bridging Study of Oral ASTX727 Versus IV Decitabine in Chinese Subjects With Myelodysplastic Syndromes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06091267
• Other study ID #: 393-403-00072
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 16, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: October 2023
• Source: Otsuka Beijing Research Institute
• Contact: Lei Cui
• Phone: +86 13161762886
• Email: cuilei[@]cn.otsuka.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an Open-Label, Crossover, Pharmacokinetic and Efficacy Bridging Study of Oral ASTX727 versus IV Decitabine in Chinese Subjects with Myelodysplastic Syndromes

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: June 30, 2026
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Agree to participate in this trial and voluntarily sign the informed consent form.

2. Men or women = 18 years at the time of signing the informed consent form.

3. Subjects with MDS previously treated or untreated with de novo or secondary MDS.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at screening.

Exclusion Criteria:

1. Prior treatment with more than 1 cycle of azacitidine or decitabine.

2. Cytotoxic chemotherapy or prior azacitidine or decitabine within 4 weeks of first dose of study treatment.

3. Conditions as judged by the investigator to be inappropriate for participation in the clinical trial.

4. Previous diagnosis of malignant tumor.

5. History of immune deficiency.

6. Acute myeloid leukemia (AML) with bone marrow or peripheral blast count = 20% or other malignant hematological diseases.

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• IV Decitabine
The subjects will receive decitabine 20 mg/m^2 IV daily × 5 days in 28-day cycles.
• Decitabine and cedazuridine
subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles.
• only Decitabine and cedazuridine
subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles, until disease progression, unacceptable toxicity, or the subject/investigator decides that the subject should discontinue treatment or withdraw from the trial.

Locations

Country	Name	City	State
China	The First Affiliated Hospital,Zhejiang University School of Medicine	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Beijing Research Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate	Assess efficacy [Complete Response Rate (CR)] of treatment with ASTX727 in Chinese subjects with myelodysplastic syndromes (MDS);	An analysis is planned when the last enrolled patient have completed Follow-up 12 months.
Primary	5day_AUC0-t	Assess pharmacokinetic (PK) parameters (Total 5-day AUC exposures of decitabine) after treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 days;	An analysis is planned when the last enrolled patient have completed the treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 day.
Secondary	Objective Response Rate	Objective Response Rate (ORR): The proportion of subjects who achieve CR and partial response (PR) based on IWG 2006 criteria;	through study completion, an average of 1 year.
Secondary	Clinical Response Rate	Clinical Response Rate: The proportion of subjects who achieve CR, PR, marrow complete response (mCR), and hematologic improvement (HI) based on IWG 2006 criteria.	through study completion, an average of 1 year.
Secondary	Rate of transfusion independence	Rate of transfusion independence: The proportion of subjects who had no blood transfusion of 2 or more units of PRBCs for 56 days or more after treatment;	through study completion, an average of 1 year.
Secondary	disease progression	Time to progression to acute myeloid leukemia (AML);	through study completion, an average of 1 year.
Secondary	Overall survival	Overall survival (OS).	through study completion, an average of 1 year.
Secondary	Safety assessment	Safety as assessed by adverse events (AEs), concomitant medications, physical examination, clinical laboratory tests (hematology , serum chemistry and urinalysis), vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, and electrocardiogram (ECG).	through study completion, an average of 1 year.
Secondary	peak concentration (Cmax)	Decitabine PK parameters: peak concentration (Cmax).	through study completion, an average of 1 year.
Secondary	time to peak concentration (Tmax)	Decitabine PK parameters: time to peak concentration (Tmax).	through study completion, an average of 1 year.
Secondary	area under the plasma concentration-time curve over a dosing interval (AUC0-t).	Decitabine PK parameters: area under the plasma concentration-time curve over a dosing interval (AUC0-t).	through study completion, an average of 1 year.
Secondary	accumulation ratio based on AUC0-t (Rac_AUC0-t).	Decitabine PK parameters: accumulation ratio based on AUC0-t (Rac_AUC0-t).	through study completion, an average of 1 year.
Secondary	accumulation ratio based on Cmax (Rac_Cmax).	Decitabine PK parameters: accumulation ratio based on Cmax (Rac_Cmax).	through study completion, an average of 1 year.
Secondary	Cmax	PK parameters of E7727 and E7727-epimer: Cmax.	through study completion, an average of 1 year.
Secondary	Tmax	PK parameters of E7727 and E7727-epimer: Tmax.	through study completion, an average of 1 year.
Secondary	AUC0-t	PK parameters of E7727 and E7727-epimer: area under the plasma concentration-time curve over a dosing interval .	through study completion, an average of 1 year.
Secondary	Rac_AUC0-t	PK parameters of E7727 and E7727-epimer: accumulation ratio based on AUC0-t.	through study completion, an average of 1 year.
Secondary	Rac_Cmax	PK parameters of E7727 and E7727-epimer: accumulation ratio based on Cmax.	through study completion, an average of 1 year.