Phase I/II Study of Linperlisib Plus Chidamide for R/R Cutaneous T-cell Lymphoma: a Prospective, Single-center Study
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Recommended phase 2 dose (RP2D)（Phase 1） [4 weeks since the date of first dose]
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.
- Objective response rate (ORR)（Phase 2） [evaluated every 3 months (up to 24 months）]
Secondary Outcome Measures
- Progression-free survival [Baseline up to data cut-off (up to 5 years)]
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.
- Overall survival [Baseline up to data cut-off (up to 5 years)]
Overall survival was defined as the time from the date of enrollment to the date of death from any cause.
- complete remission (CR) rate [evaluated every 3 months (up to 24 months）]
Treatment responses were assessed according to the 2014 Lugano classification criteria
- adverse events [evaluated every treatment cycle (up to 24 months）]
Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Eligibility Criteria
Criteria
Inclusion Criteria:
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Ages 18-75;
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Mycosis fungoides and Sezary syndrome confirmed by histopathology;
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Patients with measurable lesions, with or without extra-cutaneous lesions, and clinical stage IIB-IVB;
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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.);
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ECOG score of 0-2;
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Adequate bone marrow hematopoietic function: neutrophil count (ANC) ≥1.5×109/L, platelet count (PLT) ≥80×109/L, hemoglobin (HGB) ≥90g/L;
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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:
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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;
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Uncontrolled active infections;
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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)
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Pregnant or lactating women;
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Investigators judged that they were not suitable to participate in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking Union Medical College Hospital | Beijing | Beijing | China | 100730 |
Sponsors and Collaborators
- Peking Union Medical College Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PUMCH-NHL-015