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

Study Overview
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Brief Summary
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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.

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

Conditions
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Cutaneous T-cell Lymphoma

Intervention / Treatment
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* Drug: Linperlisib in combined with Chidamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Linperlisib + Chidamide<br>Linperlisib combined with chidamide | Drug: Linperlisib in combined with Chidamide<br>* 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<br>|

What is the study measuring?
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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） |