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

Cutaneous T-cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06037239
• Other study ID #: PUMCH-NHL-015
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 1, 2023
• Est. completion date: July 2025

Study information

• Verified date: July 2023
• Source: Peking Union Medical College Hospital
• Contact: Wei Zhang
• Phone: +8613681473557
• Email: vv1223[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: July 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cutaneous T-cell Lymphoma
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral

Intervention

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

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Objective response rate (ORR)(Phase 2)		evaluated every 3 months (up to 24 months)
Secondary	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)
Secondary	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)
Secondary	complete remission (CR) rate	Treatment responses were assessed according to the 2014 Lugano classification criteria	evaluated every 3 months (up to 24 months)
Secondary	adverse events	Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	evaluated every treatment cycle (up to 24 months)