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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 134
- 试验地点
- 6
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Phase Ib: Dose-escalation cohort
Linperlisib was administered in three dose groups of 40 mg, 60 mg, and 80 mg once daily (QD), with each group enrolling 3-6 patients with newly diagnosed or relapsed/refractory PTCL. Chidamide was given at a fixed dose of 20 mg twice weekly. During the 21-day DLT (dose-limiting toxicity) observation period, the maximum tolerated dose (MTD) of linperlisib was assessed, and the recommended phase II dose (RP2D) was determined for use in the phase II study.
干预措施: Linperlisib and chidamide (Drug)
Phase IIa: Expansion cohort
In newly diagnosed PTCL patients, the efficacy and safety of Linperlisib (RP2D) combined with Chidamide were evaluated. Each treatment cycle is 3 weeks, and patients who responded effectively would receive a total of six cycles of therapy.
干预措施: Linperlisib and chidamide (Drug)
Phase IIb: Randomized controlled study: experimental arm
Patients randomized to the experimental group will receive combination therapy with Linperlisib and Chidamide.
干预措施: Linperlisib and chidamide (Drug)
Phase IIb: Randomized controlled study: Control arm
Patients randomized to the control group will receive conventional CHOP or CHOP-like regimen chemotherapy.
干预措施: cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: Approximately 3 months
Phase Ib
CRR (Complete response rate)
时间窗: Through study completion, an average of 3 years
Phase IIa and IIb
次要结局
- PFS (progression-free survival)(Through study completion, an average of about 3 years)
- OS(Through study completion, an average of about 3 years)
- AE (Adverse event)(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)(Cycle 1 Day 1 through follow-up period)
- Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy -Lymphoma (FACT-Lym) Subscale(Cycle 1 Day 1 through follow-up period)
研究者
Yanyan Liu
Professor
Henan Cancer Hospital