Myelodysplastic Syndromes
Conditions
Brief summary
This is an Open-Label, Crossover, Pharmacokinetic and Efficacy Bridging Study of Oral ASTX727 versus IV Decitabine in Chinese Subjects with Myelodysplastic Syndromes
Interventions
DRUGDecitabine and cedazuridine
subjects will receive treatment with ASTX727, 1 tablet/day for 5 consecutive days, in 28-day cycles.
DRUGIV Decitabine
The subjects will receive decitabine 20 mg/m\^2 IV daily × 5 days in 28-day cycles.
DRUGonly 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.
Sponsors
Otsuka Beijing Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | An analysis is planned when the last enrolled patient have completed Follow-up 12 months. | Assess efficacy \[Complete Response Rate (CR)\] of treatment with ASTX727 in Chinese subjects with myelodysplastic syndromes (MDS); |
| 5day_AUC0-τ | An analysis is planned when the last enrolled patient have completed the treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 day. | Assess pharmacokinetic (PK) parameters (Total 5-day AUC exposures of decitabine) after treatment with ASTX727 (oral) versus decitabine for IV infusion for 5 days; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | through study completion, an average of 1 year. | Objective Response Rate (ORR): The proportion of subjects who achieve CR and partial response (PR) based on IWG 2006 criteria; |
| Clinical Response Rate | through study completion, an average of 1 year. | Clinical Response Rate: The proportion of subjects who achieve CR, PR, marrow complete response (mCR), and hematologic improvement (HI) based on IWG 2006 criteria. |
| Rate of transfusion independence | through study completion, an average of 1 year. | 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; |
| disease progression | through study completion, an average of 1 year. | Time to progression to acute myeloid leukemia (AML); |
| Overall survival | through study completion, an average of 1 year. | Overall survival (OS). |
| Safety assessment | through study completion, an average of 1 year. | 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). |
| peak concentration (Cmax) | through study completion, an average of 1 year. | Decitabine PK parameters: peak concentration (Cmax). |
| time to peak concentration (Tmax) | through study completion, an average of 1 year. | Decitabine PK parameters: time to peak concentration (Tmax). |
| area under the plasma concentration-time curve over a dosing interval (AUC0-τ). | through study completion, an average of 1 year. | Decitabine PK parameters: area under the plasma concentration-time curve over a dosing interval (AUC0-τ). |
| accumulation ratio based on AUC0-τ (Rac_AUC0-τ). | through study completion, an average of 1 year. | Decitabine PK parameters: accumulation ratio based on AUC0-τ (Rac\_AUC0-τ). |
| accumulation ratio based on Cmax (Rac_Cmax). | through study completion, an average of 1 year. | Decitabine PK parameters: accumulation ratio based on Cmax (Rac\_Cmax). |
| Cmax | through study completion, an average of 1 year. | PK parameters of E7727 and E7727-epimer: Cmax. |
| Tmax | through study completion, an average of 1 year. | PK parameters of E7727 and E7727-epimer: Tmax. |
| AUC0-τ | through study completion, an average of 1 year. | PK parameters of E7727 and E7727-epimer: area under the plasma concentration-time curve over a dosing interval . |
| Rac_AUC0-τ | through study completion, an average of 1 year. | PK parameters of E7727 and E7727-epimer: accumulation ratio based on AUC0-τ. |
| Rac_Cmax | through study completion, an average of 1 year. | PK parameters of E7727 and E7727-epimer: accumulation ratio based on Cmax. |
Countries
China
Outcome results
None listed