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Linperlisib Combined With Chidamide in Patients With PTCL

ConditionPeripheral T-cell Lymphoma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorYanyan Liu

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18-75 years at the time of inclusion (Age 18-80 years for phase Ib and IIa study)

Patients with a newly diagnosed and histologically confirmed PTCL (phase Ib study includes both newly diagnosed and relapsed/refractory PTCL). Anaplastic large cell lymphoma, NK/T-cell lymphoma, and primary cutaneous T-cell lymphoma are not included.

ECOG PS 0-2 at protocol entry

Estimated life expectancy of 6 months or longer

Disqualifiers

Patients previously treated with PI3K inhibitor

Patients previously treated with chidamide (phase Ib study is not limited by this item)

Suspected or documented central nervous system involvement by lymphoma

Patients with positive HIV and/or active hepatitis B and/or hepatitis C infection

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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.

Treatment groups

134 Participants
are divided into 4 treatment groups
Group A: Phase Ib: Dose-escalation cohortExperimental treatment 1 intervention
Group B: Phase IIa: Expansion cohortExperimental treatment 1 intervention
Group C: Phase IIb: Randomized controlled study: experimental armExperimental treatment 1 intervention
Group D: Phase IIb: Randomized controlled study: Control armActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Recommended Phase 2 Dose (RP2D)

Phase Ib

Time frame
Approximately 3 months
2

CRR (Complete response rate)

Phase IIa and IIb

Time frame
Through study completion, an average of 3 years

Secondary outcomes

1

PFS (progression-free survival)

Phase IIa and IIb

Time frame
Through study completion, an average of about 3 years
2

OS

Phase IIa and IIb

Time frame
Through study completion, an average of about 3 years
3

AE (Adverse event)

Phase Ib, IIa and IIb

Time frame
Through study completion, an average of 3 years
4

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

Time frame
Cycle 1 Day 1 through follow-up period

Other outcomes

1

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).

Time frame
Through study completion, an average of about 3 years
2

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).

Time frame
Through study completion, an average of about 3 years
3

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......)

Time frame
Through study completion, an average of about 3 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Yanyan Liu

Lead sponsor

Henan Cancer Hospital

Sponsor institution

Source ClinicalTrials.gov
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