Linperlisib Combined With Chidamide in Patients With PTCL

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Linperlisib and chidamide
  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 r
• Препарат Linperlisib and chidamide
  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.
• Препарат Linperlisib and chidamide
  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.
• Препарат cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone
  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.

Первичные конечные точки

• Recommended Phase 2 Dose (RP2D) [Срок оценки: Approximately 3 months]
• CRR (Complete response rate) [Срок оценки: Through study completion, an average of 3 years]

Вторичные конечные точки (5)

• PFS (progression-free survival) [Срок оценки: Through study completion, an average of about 3 years]
• OS [Срок оценки: Through study completion, an average of about 3 years]
• AE (Adverse event) [Срок оценки: 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) [Срок оценки: Cycle 1 Day 1 through follow-up period]
• Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy -Lymphoma (FACT-Lym) Subscale [Срок оценки: Cycle 1 Day 1 through follow-up period]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 6 центров

• Affiliated Cancer Hospital of Zhengzhou University — Чжэнчжоу
• Liling Zhang — Ухань
• Yajun Li — Чанша
• Ming Jiang — Чэнду
• Huilai Zhang — Тяньцзинь
• Cong Li — Ханчжоу

Идентификаторы

NCT: NCT06421948 · HNSZLYYML08

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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