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The phase Ib part of this study aims to determine the recommended phase II dose （RP2D）of linperlisib in combination with chidamide for the treatment of peripheral T-cell lymphoma (PTCL).
The phase IIa part is designed to evaluate the preliminary efficacy and safety of the linperlisib plus chidamide regimen in newly diagnosed PTCL patients.
The phase IIb part compares the efficacy and safety of linperlisib combined with chidamide versus the standard CHOP (CHOP-like) regimen in newly diagnosed PTCL patients.
In the phase Ib trial, participants with newly diagnosed or relapsed/refractory PTCL will receive fixed dose of chidamide (20 mg, twice a week) and escalating dose of linperlisib (40 mg, 60 mg, or 80 mg, once a day), to find out the RP2D.
The phase IIa study is an exploratory efficacy study enrolling newly diagnosed PTCL patients who receive linperlisib in combination with chidamide to evaluate the efficacy and safety of the regimen.
In the phase IIb study, participants with newly diagnosed PTCL will be randomized into experimental arm (arm A) to receive linperlisib in combination with chidamide, or control arm (arm B) to receive standard CHOP (or CHOP-like) regimen chemotherapy.
Interim efficacy assessment will be performed after three cycles of treatment. Responded participants will receive another three cycles of treatment. After a total of 6 cycles of treatment, participants can choose autologous hematopoietic stem cell transplantation, maintenance treatment with linperlisib and/or chidamide, or watch and wait.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase Ib: Dose-escalation cohort | Experimental | Linperlisib was administered in three dose groups of 40 mg, 60 mg, and 80 mg once daily (QD), with each group enrolling 3-6 patients with newly diagnosed or relapsed/refractory PTCL. Chidamide was given at a fixed dose of 20 mg twice weekly. During the 21-day DLT (dose-limiting toxicity) observation period, the maximum tolerated dose (MTD) of linperlisib was assessed, and the recommended phase II dose (RP2D) was determined for use in the phase II study. |
|
| Phase IIa: Expansion cohort | Experimental | In newly diagnosed PTCL patients, the efficacy and safety of Linperlisib (RP2D) combined with Chidamide were evaluated. Each treatment cycle is 3 weeks, and patients who responded effectively would receive a total of six cycles of therapy. |
|
| Phase IIb: Randomized controlled study: experimental arm | Experimental | Patients randomized to the experimental group will receive combination therapy with Linperlisib and Chidamide. |
|
| Phase IIb: Randomized controlled study: Control arm | Active Comparator | Patients randomized to the control group will receive conventional CHOP or CHOP-like regimen chemotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linperlisib and chidamide | Drug | Linperlisib is a selective PI3Kδ inhibitor that has been approved in mainland China for the treatment of relapsed or refractory follicular lymphoma, with a recommended monotherapy dose of 80 mg orally once daily. In this study, Linperlisib was administered at three dose levels of 40 mg, 60 mg, and 80 mg in order to determine the recommended Phase II dose (RP2D) when combined with a fixed dose of Chidamide (20 mg twice weekly). Chidamide has been approved in mainland China for the treatment of relapsed or refractory PTCL and double-expressor DLBCL. In this study, it was administered at a fixed dose of 20 mg twice weekly in combination with Linperlisib. |
| Measure | Description | Time Frame |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) | Phase Ib | Approximately 3 months |
| CRR (Complete response rate) | Phase IIa and IIb | Through study completion, an average of 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| PFS (progression-free survival) | Phase IIa and IIb | Through study completion, an average of about 3 years |
| OS | Phase IIa and IIb | Through study completion, an average of about 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between baseline tumor gene mutation profile and clinical efficacy (CRR, PFS, OS) | Phase Ib, IIa and IIb Baseline tumor tissue will be analyzed using a targeted next-generation sequencing (NGS) panel to determine the tumor gene mutation profile, including the presence of predefined somatic mutations. Clinical efficacy will be evaluated by CRR, PFS, and OS as defined in the protocol. The correlations between baseline tumor gene mutation profile and CRR, PFS, and OS will be explored using appropriate statistical methods (Chi-square Test, Fisher's Exact Test, Log-rank, logistic regression, and Cox proportional hazards models). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yanyan Liu | Contact | 86 037165587791 | yyliu@zzu.edu.cn | |
| Zheng Yan | Contact | 86 13598097015 | zlyyyanzheng3920@zzu.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Yanyan Liu | A | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Affiliated Cancer Hospital of Zhengzhou University | Recruiting | Zhengzhou | Henan | 450008 | China |
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| ID | Term |
|---|---|
| D016411 | Lymphoma, T-Cell, Peripheral |
| ID | Term |
|---|---|
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C547816 | N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide |
| D003520 | Cyclophosphamide |
| D004317 | Doxorubicin |
| D015251 | Epirubicin |
| D014750 | Vincristine |
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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|
| Linperlisib and chidamide | Drug | All patients received Linperlisib at the RP2D dose once daily and Chidamide 20 mg twice weekly, with each treatment cycle lasting 3 weeks. After three cycles, an interim efficacy assessment was performed. Patients who showed a therapeutic response received an additional three cycles, and the final efficacy evaluation was conducted after six cycles. |
|
| Linperlisib and chidamide | Drug | Patients received Linperlisib at the RP2D dose once daily and Chidamide 20 mg twice weekly, with each treatment cycle lasting 3 weeks. After three cycles, an interim efficacy assessment was performed. Patients who showed a therapeutic response received an additional three cycles, and the final efficacy evaluation was conducted after six cycles. |
|
| cyclophosphamide, doxorubicin/epirubicin, vincristine, and prednisone | Drug | Patients receive conventional CHOP (or CHOP-like regimens such as CHOPE or EPOCH) chemotherapy, with 3 weeks for one cycle. After three cycles, an interim efficacy assessment was performed. Patients who showed a response received an additional three cycles, and the final efficacy evaluation was conducted after six cycles. |
|
| AE (Adverse event) | Phase Ib, IIa and IIb | Through study completion, an average of 3 years |
| Physical Functioning and Fatique as Measured by the European Organization for Research and Treatment of Cancer Quality of Life - Core 30 Questionnaire (EORTCQLQ-C30) | Phase IIb | Cycle 1 Day 1 through follow-up period |
| Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy -Lymphoma (FACT-Lym) Subscale | Phase IIb | Cycle 1 Day 1 through follow-up period |
| Through study completion, an average of about 3 years |
| Correlation between plasma circulating tumor DNA (ctDNA) levels and clinical efficacy (CRR, PFS, OS) | Plasma circulating tumor DNA (ctDNA) will be measured at baseline and at predefined on-treatment time points using a next-generation sequencing (NGS)-based assay. ctDNA will be quantified as variant allele frequency (VAF, %) and/or copies per milliliter (copies/mL). Clinical efficacy will be evaluated by CRR, PFS, and OS as defined in the protocol. Exploratory analyses will assess the correlations between baseline ctDNA levels, on-treatment ctDNA levels, and changes from baseline in ctDNA, and clinical efficacy outcomes (CRR, PFS, OS) using appropriate statistical methods (Kaplan-Meier Curves, Cox Proportional Hazards Model, Linear Regression Analysis, Generalized Estimating Equations/Mixed Effects Models, Receiver Operating Characteristic [ROC] Curve,Time-dependent Cox Regression Model, Mixed Effects Models, Multiple Comparison Correction, Spearman Rank Correlation, Group Comparisons, and Multivariate Regression Analysis). | Through study completion, an average of about 3 years |
| Correlation between tumor microenvironment characteristics assessed by single-cell sequencing and clinical efficacy (CRR, PFS, OS) | Tumor microenvironment characteristics will be assessed using single-cell sequencing or flow cytometry of tumor tissue obtained at baseline (and, if available, at on-treatment time points). Parameters of interest may include the composition and abundance of immune cell subsets (CD8+ T cells, regulatory T cells, NK cell, macrophage subpopulations) and their gene-expression signatures. These variables will be quantified as the proportion of each cell subset among total viable cells (%) or as gene-expression scores. Clinical efficacy will be evaluated by CRR, PFS, and OS as defined in the protocol. The correlations between tumor microenvironment features (e.g., immune cell subset composition and gene-expression-based signatures) and clinical efficacy outcomes (CRR, PFS, OS) will be explored using appropriate statistical methods (Kaplan-Meier Curves, Cox Proportional Hazards Model, Multivariate Cox Regression, Multivariate Logistic Regression, Linear and Logistic Regression......) | Through study completion, an average of about 3 years |
| Liling Zhang | Recruiting | Wuhan | Hubei | 430022 | China |
|
| Yajun Li | Recruiting | Changsha | Hunan | 410003 | China |
|
| Ming Jiang | Recruiting | Chengdu | Sichuan | 610041 | China |
|
| Huilai Zhang | Recruiting | Tianjin | Tianjin Municipality | 300060 | China |
|
| Cong Li | Recruiting | Hangzhou | Zhejiang | 310000 | China |
|
| D009369 |
| Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |