Linperlisib Combined With Chidamide in Patients With PTCL

Phase 2RecruitingNCT06421948

Yanyan Liu134 enrolled

Overview

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.

In the phase Ib trial, participants with newly diagnosed or relapsed/refractory PTCL will receive fixed dose of chidamide (20 mg, twice a week) and escalating dose of linperlisib (40 mg, 60 mg, or 80 mg, once a day), to find out the RP2D. The phase IIa study is an exploratory efficacy study enrolling newly diagnosed PTCL patients who receive linperlisib in combination with chidamide to evaluate the efficacy and safety of the regimen. In the phase IIb study, participants with newly diagnosed PTCL will be randomized into experimental arm (arm A) to receive linperlisib in combination with chidamide, or control arm (arm B) to receive standard CHOP (or CHOP-like) regimen chemotherapy. Interim efficacy assessment will be performed after three cycles of treatment. Responded participants will receive another three cycles of treatment. After a total of 6 cycles of treatment, participants can choose autologous hematopoietic stem cell transplantation, maintenance treatment with linperlisib and/or chidamide, or watch and wait.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

134

Conditions

Peripheral T-cell Lymphoma

Interventions

Linperlisib and chidamideDRUG

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.

Linperlisib and chidamideDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Criteria: * 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

Locations (6)

Affiliated Cancer Hospital of Zhengzhou University

Zhengzhou, Henan, China

RECRUITING

Liling Zhang

Wuhan, Hubei, China

RECRUITING

Yajun Li

Changsha, Hunan, China

Outcomes

Primary Outcomes

Recommended Phase 2 Dose (RP2D)

Phase Ib

Time frame: Approximately 3 months

CRR (Complete response rate)

Phase IIa and IIb

Time frame: Through study completion, an average of 3 years

Secondary Outcomes

PFS (progression-free survival)

Phase IIa and IIb

Time frame: Through study completion, an average of about 3 years

Phase IIa and IIb

Time frame: Through study completion, an average of about 3 years

AE (Adverse event)

Phase Ib, IIa and IIb

Time frame: Through study completion, an average of 3 years

Physical Functioning and Fatique as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTCQLQ-C30)

Phase IIb

Time frame: Cycle 1 Day 1 through follow-up period

Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy -Lymphoma (FACT-Lym) Subscale

Phase IIb

Time frame: Cycle 1 Day 1 through follow-up period

Central Contacts

Yanyan Liu

CONTACT

86 037165587791 yyliu@zzu.edu.cn

Zheng Yan

CONTACT

86 13598097015 zlyyyanzheng3920@zzu.edu.cn

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.