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

Phase I/II Study of Linperlisib in Combination With Chidamide for Relapsed and Refractory Cutaneous T-cell Lymphoma: a Prospective, Single-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 against relapsed and refractory T-cell lymphomas including cutaneous T-cell lymphomas (CTCLs). 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 CTCLs.

Study Overview

• Status: Recruiting
• Conditions: Cutaneous T-cell Lymphoma
• Intervention / Treatment: Drug: Linperlisib in combined with Chidamide

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Chong Wei; Phone Number: +8613521760705; Email: QH5035@163.com
• Study Contact Backup: Name: Wei Zhang; Phone Number: +8613681473557; Email: vv1223@vip.sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Zhang Wei; Phone Number: +86 136 8147 3557; Email: vv1223@vip.sina.com
      • Contact: Wei Chong; Phone Number: +86 13521760705; Email: QH5035@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ages 18-75;
• Mycosis fungoides and Sezary syndrome confirmed by histopathology;
• Patients with measurable lesions, with or without extra-cutaneous lesions, and clinical stage IIB-IVB;
• No remission or relapse after at least one systemic therapy (including total body electron irradiation, becarodine, retinoic acid, interferon, photoseparation and replacement, methotrexate, chidamide, etc.);
• 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<2.5UNL, TBil<1.5ULN, SPO2 > 93%@RA, SCr>60ml/(min·1.73m2);

Exclusion Criteria:

• 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;
• Investigators judged that they were not suitable to participate in the study

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 + 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. 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)（Phase 1）	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)（Phase 2）		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.	Baseline up 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.	Baseline up 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 4.0	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): July 1, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 14, 2023

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: July 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; Lymphoma, T-Cell, Cutaneous
• Other Study ID Numbers: PUMCH-NHL-015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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