Phase I/II Study of Linperlisib Plus Chidamide for R/R Peripheral T-cell Lymphoma: a Prospective, Multi-center Study

Phase I/II Study of Linperlisib in Combination With Chidamide for Relapsed and Refractory Peripheral T-cell Lymphoma: a Prospective, Multi-center Study

HDAC inhibitor chidamide and PI3K inhibitor linperlisib has shown clinical activity as mono-therapy in PTCL. The combination of duvelisib and romidepsin is highly active for relapsed and refractory PTCLs. The aim of this study is to further explore the efficacy and safety of HDAC inhibitor chidamide combined with PI3K inhibitor linperlisib in the treatment of relapsed and refractory PTCLs.

Study Overview

• Status: Recruiting
• Conditions: Peripheral T Cell Lymphoma
• Intervention / Treatment: Drug: Linperlisib in combined with Chidamide

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chong Wei, Dr; Phone Number: +86 13521760705; Email: QH5035@163.com
• Study Contact Backup: Name: Daobin Zhou, Dr; Phone Number: +8613901113623; Email: Zhoudb@pumch.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Beijing Hospital
    • Contact: Hui Liu
  • Beijing/China
    • Beijing, Beijing/China, China, 100000
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Daobin Zhou, PhD&MD; Phone Number: 010-69155020; Email: zhoudb@pumch.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ages 18-75;
• Pathologically confirmed diagnosis of PTCL, not otherwise specified (PTCL, NOS), anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), or other PTCL subtypes that the researchers considered to be eligible;
• Fulfills the criteria for relapsed/refractory lymphoma;
• There must be at least one measurable lesion: for measurable lymph node, the longest diameter should be > 1.5cm, for measurable extranodal lesion, the longest diameter should be > 1.0cm;
• ECOG score of 0-2;

• Adequate bone marrow hematopoietic function: neutrophil count (ANC)

  ≥1.5×109/L, platelet count (PLT) ≥80×109/L, hemoglobin (HGB) ≥90g/L;

• Adequate organ function: NYHA grade 1-2, LVEF≥50%, ALT<3UNL, TBil<2ULN, SPO2 > 93%@RA, SCr>60ml/(min·1.73m2);

Exclusion Criteria:

• Extranodal natural killer/T cell lymphoma;
• Previously treated with PI3K inhibitors;
• Acute myocardial infarction or unstable angina, congestive heart failure, symptomatic arrhythmia, and significantly prolonged QT interval (> 450ms in men and > 470ms in women) within 6 months;
• Uncontrolled active infections;
• Active hepatitis B and C infection (hepatitis B virus DNA over 1×103 copies /mL is excluded, hepatitis C virus RNA over 1×103 copies /mL is excluded);
• Pregnant or lactating women;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linperlisib plus Chidamide; Linperlisib combined with chidamide	Drug: Linperlisib in combined with Chidamide; Phase 1: dose escalation phase. Drug Linperlisib: 3 dose level of 40mg, 60mg, 80mg qd; Drug Chidamide: fixed dose of 20mg twice weekly in a 4-week cycle;; Phase 2: dose expansion phase. Drug Linperlisib: RP2D established in the phase I study; Drug Chidamide: fixed dose of 20mg twice weekly in a 4-week cycle;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended phase 2 dose (RP2D)	Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) will be established according to the incidence of dose-limiting toxicities (DLTs) of escalated doses of linperlisib.	4 weeks since the date of first dose
Objective response rate (ORR)	Objective response rate (ORR) for phase 2 study	evaluated every 3 months (up to 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Progression-free survival was defined as the time from the date of enrollment until the date of the first documented day of disease progression or relapse, or death from any cause, whichever occurred first.	recruitment to data cut-off (up to 5 years)
Overall survival	Overall survival was defined as the time from the date of enrollment to the date of death from any cause.	recruitment to data cut-off (up to 5 years)
complete remission (CR) rate	Treatment responses were assessed according to the 2014 Lugano classification criteria	evaluated every 3 months (up to 24 months)
adverse events	Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	evaluated every treatment cycle (up to 24 months)

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2023
• Primary Completion (Estimated): September 25, 2024
• Study Completion (Estimated): September 25, 2025

Study Registration Dates

• First Submitted: October 9, 2023
• First Submitted That Met QC Criteria: October 9, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: September 1, 2023

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
• Other Study ID Numbers: PUMCH-NHL-016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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