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

The goal of this clinical trial is to determine the maximum tolerated dose (MTD) of PI3Kδ inhibitor linperlisib when combined with fixed dose of HDAC inhibitor chidamide in participants with peripheral T-cell lymphoma (PTCL), and to compare the combination of linperlisib and chidamide to standard CHOP (cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone) regimen chemotherapy in the frontline treatment of PTCL to see which therapy is better.

Study Overview

• Status: Recruiting
• Conditions: Peripheral T-cell Lymphoma
• Intervention / Treatment: Drug: Linperlisib and chidamide; Drug: cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone

Detailed Description

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 optimal dose of linperlisib.

In the phase II trial, 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 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
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yanyan Liu; Phone Number: 86 037165587791; Email: yyliu@zzu.edu.cn
• Study Contact Backup: Name: Zheng Yan; Phone Number: 86 13598097015; Email: zlyyyanzheng3920@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Recruiting
      • Affiliated Cancer Hospital of Zhengzhou University
      • Contact: Yanyan Liu; Phone Number: 86-037165587791; Email: yyliu@zzu.edu.cn
      • Contact: Zheng Yan; Phone Number: 86+13598097015; Email: zlyyyanzheng3920@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-75 years at the time of inclusion (Age 18-80 years for phase Ib 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 and NK/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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orally administered, targeted therapy; Participants will receive a combination of linperlisib in combination with chidamide orally.	Drug: Linperlisib and chidamide; A combination of linperlisib and chidamide will be administered for 6 cycles in patients responded to treatment.
Active Comparator: Intravenously chemotherapy; Participants will receive standard CHOP regimen chemotherapy including cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone.	Drug: cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone; A combination of cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone (CHOP) will be administered for 6 cycles in patients responded to treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRR	Complete response rate	Through study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	12 months
PFS	Progression-free survival	12 months
AE	Adverse event	Through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: Yanyan Liu
• Investigators: Principal Investigator: Yanyan Liu, A

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Epirubicin; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: HNSZLYYML08

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No