In this study, the XNW5004 tablets combined with CHOP/CHOEP will be used for the treatment of newly diagnosed PTCL patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
176
The XNW5004 protocol has preset four dosage groups: 400mg, 800mg, 1200mg and 1600mg, administered twice daily (BID). The CHOP regimen is administered at a fixed dose, for a total of 6 cycles. After completing the combined treatment and without disease progression, the subjects will continue to receive XNW5004 at 1200mg BID for maintenance therapy.
It is expected to conduct dose escalation studies for XNW5004 in combination with CHOEP using 1-3 dose groups. The CHOEP regimen will be administered at a fixed dose for a total of 6 cycles. After completing the combined treatment and without disease progression, the subjects will continue to receive XNW5004 at 1200mg BID for maintenance therapy.
Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITINGIb/II:Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability].
Incidence and severity of adverse events that are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Time frame: through study completion, an average of 1 year
II:Objective response rate (ORR)
ORR is defined as the proportion of subjects who have a confirmed CR or a PR per lugano2014 assessed by Investigator.
Time frame: 36 months
Ib:Maximum tolerated dose (MTD) and/or the recommended Part 2 dose
To determine the maximum tolerated dose (MTD) and the recommended Part 2 dose with XNW5004.
Time frame: The first 21-day cycle of therapy
Ib/II:The maximum (peak) blood drug concentration (Cmax) is XNW5004
Collect blood samples at the specified intervals to determine the Cmax.
Time frame: through study completion, an average of 1 year
Ib/II:XNW5004 Peak Time (Tmax)
Collect blood samples at the specified intervals to determine the Tmax.
Time frame: through study completion, an average of 1 year
Ib/II:The area under the blood drug concentration-time curve of XNW5004 (AUC)
Collect blood samples at specified intervals to determine AUC
Time frame: through study completion, an average of 1 year
Ib/II:The maximum (peak) blood drug concentration in the steady state (Css,max)
Collect blood samples at specified intervals to determine Css,max
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Those who received the combination treatment of XNW5004 and CHOP, and who did not experience disease progression after the combined treatment, will continue to receive maintenance treatment with XNW5004 at a dose of 1200mg twice daily.
Those who received the combination treatment of XNW5004 and CHOEP, and who did not experience disease progression after the combined treatment, will continue to receive maintenance treatment with XNW5004 at a dose of 1200mg twice daily.
Time frame: through study completion, an average of 1 year
Ib/II:XNW5004 Steady-state Baseline Concentration (Css, min)
Collect blood samples at specified intervals to determine Css, min
Time frame: through study completion, an average of 1 year
Ib/II:The area under the blood drug concentration-time curve (AUCss) under steady-state conditions of XNW5004
Collect blood samples at specified intervals to determine AUCss
Time frame: through study completion, an average of 1 year
Ib/II:XNW5004 Elimination Half-Life (T1/2)
Collect blood samples at specified intervals to determine T1/2
Time frame: through study completion, an average of 1 year
Ib/II:Pharmacodynamic indicators, the relative change of H3K27me3 (trimethylation of lysine at position 27 of histone H3) compared to the baseline of histone H3
Collect blood samples at the specified time to determine the relative changes of H3K27me3 (trimethylation of lysine at position 27 of histone H3) compared to the baseline.
Time frame: through study completion, an average of 1 year
Ib/II:Objective Response Rate (ORR)
ORR is defined as the Lugano 2014 assessment, representing the proportion of subjects who were diagnosed with CR or PR.
Time frame: 36 months
Ib/II:Disease Control Rate (DCR)
Rate of complete response \[CR\], partial response \[PR\], and stable disease per lugano2014 assessed by Investigator.
Time frame: 36 months
Ib/II:Duration of response (DOR)
Duration of response (DOR) per lugano2014 assessed by Investigator.
Time frame: 36 months
Ib/II:Progression free survival (PFS)
Progression free survival (PFS) per lugano2014 assessed by Investigator
Time frame: 36 months
Ib/II:Overall Survival (OS)
The period from when the patient begins receiving treatment until the patient dies for any reason
Time frame: 36 months