Linperlisib Combined With Chidamide in Patients With PTCL

NCT06421948 | Recruiting Phase 1

• 1 other identifier: HNSZLYYML08
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Peripheral T-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D)

  Phase Ib

  Approximately 3 months

• CRR (Complete response rate)

  Phase IIa and IIb

  Through study completion, an average of 3 years

Secondary Outcomes (5)

• 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

Other Outcomes (3)

• Correlation between baseline tumor gene mutation profile and clinical efficacy (CRR, PFS, OS)

  Through study completion, an average of about 3 years

• Correlation between plasma circulating tumor DNA (ctDNA) levels and clinical efficacy (CRR, PFS, OS)

  Through study completion, an average of about 3 years

• Correlation between tumor microenvironment characteristics assessed by single-cell sequencing and clinical efficacy (CRR, PFS, OS)

  Through study completion, an average of about 3 years

Study Arms (4)

Phase Ib: Dose-escalation cohort

EXPERIMENTAL

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.

Drug: Linperlisib and chidamide

Phase IIa: Expansion cohort

EXPERIMENTAL

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.

Drug: Linperlisib and chidamide

Phase IIb: Randomized controlled study: experimental arm

EXPERIMENTAL

Patients randomized to the experimental group will receive combination therapy with Linperlisib and Chidamide.

Drug: Linperlisib and chidamide

Phase IIb: Randomized controlled study: Control arm

ACTIVE COMPARATOR

Patients randomized to the control group will receive conventional CHOP or CHOP-like regimen chemotherapy.

Drug: cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone

Interventions

Linperlisib and chidamide DRUG

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.

Phase Ib: Dose-escalation cohort

cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone DRUG

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.

Phase IIb: Randomized controlled study: Control arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yanyan Liu: lead

Study Sites (6)

Affiliated Cancer Hospital of Zhengzhou University

Zhengzhou, Henan, 450008, China

RECRUITING

Liling Zhang

Wuhan, Hubei, 430022, China

RECRUITING

Yajun Li

Changsha, Hunan, 410003, China

RECRUITING

Ming Jiang

Chengdu, Sichuan, 610041, China

RECRUITING

Huilai Zhang

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Cong Li

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; Cyclophosphamide; Doxorubicin; Epirubicin; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Yanyan Liu

  A

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanyan Liu

CONTACT

86 037165587791; yyliu@zzu.edu.cn

Zheng Yan

CONTACT

86 13598097015; zlyyyanzheng3920@zzu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 6, 2024
• First Posted: May 20, 2024
• Study Start: May 25, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-05

Locations

CN (6)