Linperlisib Combined With Chidamide in Patients With PTCL
PI3Kδ Inhibitor Linperlisib Combined With HDAC Inhibitor Chidamide Versus CHOP in Patients With Peripheral T-cell Lymphoma: a Multicenter, Open Label, Phase Ib/II Study
Yanyan Liu
134 participants
May 25, 2024
INTERVENTIONAL
Conditions
Summary
The phase Ib part of this study aims to determine the recommended phase II dose （RP2D）of linperlisib in combination with chidamide for the treatment of peripheral T-cell lymphoma (PTCL). The phase IIa part is designed to evaluate the preliminary efficacy and safety of the linperlisib plus chidamide regimen in newly diagnosed PTCL patients. The phase IIb part compares the efficacy and safety of linperlisib combined with chidamide versus the standard CHOP (CHOP-like) regimen in newly diagnosed PTCL patients.
Eligibility
Inclusion Criteria8
- Age 18-75 years at the time of inclusion (Age 18-80 years for phase Ib and IIa study)
- Patients with a newly diagnosed and histologically confirmed PTCL (phase Ib study includes both newly diagnosed and relapsed/refractory PTCL). Anaplastic large cell lymphoma, NK/T-cell lymphoma, and primary cutaneous T-cell lymphoma are not included.
- ECOG PS 0-2 at protocol entry
- Estimated life expectancy of 6 months or longer
- Measurable disease
- Hemoglobin ≥ 8 g/dL (≥5 mmol/l); Platelets ≥ 75 x 10E9/L; Absolute neutrophil count ≥ 1.0 x 10E9/L; Platelets ≥ 50 x 10E9/L permitted if documented bone marrow involvement; Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); Serum glutamic-oxaloacetic transaminase (AST) and/or serum glutamic-pyruvic transaminase (ALT) ≤ 2.5 x ULN, or ≤ 5 x ULN if elevation is due to hepatic involvement by lymphoma; Serum creatinine ≤ 1.5 x ULNb; left ventricular ejection fraction (LVEF) ≥ 50%
- Women of childbearing potential must use safe anticonception (e.g. contraceptive pills, intrauterine devices etc.) during the study and 12 months after the last administration of study drugs; Male patients must use contraception for the duration of the study and 6 months after the last administration of study drugs if his partner is of childbearing potential
- Written informed consent
Exclusion Criteria11
- Patients previously treated with PI3K inhibitor
- Patients previously treated with chidamide (phase Ib study is not limited by this item)
- Suspected or documented central nervous system involvement by lymphoma
- Patients with positive HIV and/or active hepatitis B and/or hepatitis C infection
- Patients with active, uncontrolled infections
- Unwillingness or inability to comply with the protocol
- Deemed 'unfit' by the treating physician
- Pregnant and/or breastfeeding women
- Concurrent severe and/or uncontrolled medical disease which is not lymphoma-related
- Patients with contraindications to chemotherapy
- Known hypersensitivity to one or more of the study drugs
Interventions
Linperlisib is a selective PI3Kδ inhibitor that has been approved in mainland China for the treatment of relapsed or refractory follicular lymphoma, with a recommended monotherapy dose of 80 mg orally once daily. In this study, Linperlisib was administered at three dose levels of 40 mg, 60 mg, and 80 mg in order to determine the recommended Phase II dose (RP2D) when combined with a fixed dose of Chidamide (20 mg twice weekly). Chidamide has been approved in mainland China for the treatment of relapsed or refractory PTCL and double-expressor DLBCL. In this study, it was administered at a fixed dose of 20 mg twice weekly in combination with Linperlisib.
All patients received Linperlisib at the RP2D dose once daily and Chidamide 20 mg twice weekly, with each treatment cycle lasting 3 weeks. After three cycles, an interim efficacy assessment was performed. Patients who showed a therapeutic response received an additional three cycles, and the final efficacy evaluation was conducted after six cycles.
Patients received Linperlisib at the RP2D dose once daily and Chidamide 20 mg twice weekly, with each treatment cycle lasting 3 weeks. After three cycles, an interim efficacy assessment was performed. Patients who showed a therapeutic response received an additional three cycles, and the final efficacy evaluation was conducted after six cycles.
Patients receive conventional CHOP (or CHOP-like regimens such as CHOPE or EPOCH) chemotherapy, with 3 weeks for one cycle. After three cycles, an interim efficacy assessment was performed. Patients who showed a response received an additional three cycles, and the final efficacy evaluation was conducted after six cycles.
Locations(6)
View Full Details on ClinicalTrials.gov
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NCT06421948