A Phase I/II Study of Mitoxantrone Liposome Combined With Chidamide in Relapsed/Refractory Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous group of aggressive non-Hodgkin lymphoma (NHL) originating from mature thymus T cells.Mitoxantrone Hydrochloride Liposome Injection can accelerate the entry of mitoxantrone into cells, reduce the efflux of mitoxantrone, ensure the concentration of intracellular drugs, reverse the drug resistance mechanism, and enhance anti-tumor activity.We will explore the dose-limiting toxicity (DLT) of Mitoxantrone Hydrochloride Liposome Injection combined with Chidamide in the treatment of relapsed or refractory peripheral T-cell lymphoma, estimate the maximum tolerated dose (MTD) of the combination, and determine the phase II recommended dose RP2D.In the phase II study, we will evaluate the safety and efficacy of the combination regimen.

Detailed Description
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This study was a single-arm, open, multicenter phase I/II clinical study. An estimated 87 to 96 patients with relapsed or refractory PTCL will be enrolled. This program is divided into two parts: The phase I study is expected to enroll 9 to 18 patients with relapsed or refractory PTCL who will be treated with Mitoxantrone Hydrochloride Liposome Injection combined with Chidamide.The phase II study is expected to enroll 78 patients.

Official Title
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A Multicenter, Single-arm, Prospective Phase I/II Trial of Mitoxantrone Hydrochloride Liposome Injection Combined With Chidamide in Relapsed or Refractory Peripheral T-cell Lymphoma

Conditions
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Relapsed and Refractory Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Mitoxantrone liposome combine with Chidamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients participated voluntarily and signed informed consent； PTCL confirmed by histopathology； There must be at least one evaluable or measurable lesion that meets Lugano2014 criteria； The ECOG score is 0 to 1； ANC≥1.5×10*9/L，PLT≥75 × 10*9/L；HB≥80 g/L；TBIL≤1.5ULN；ALT or AST≤2.5 ULN； Scr≤1.5ULN； Use contraception during treatment and for one year after the end of treatment. Exclusion Criteria: Patients with central nervous system (CNS) involvement and/or hemophagocytic syndrome； The estimated survival time is less than 6 months； History of allergy to anthracyclines or liposomes; Previous recipients of mitoxantrone or mitoxantrone liposome;Previous treatment with doxorubicin or other anthracyclines had a cumulative dose of doxorubicin > 360 mg/m2（For other anthracyclines, 1 mg of doxorubicin is equivalent to 2 mg of epirubicin, and the maximum cumulative dose of liposomal doxorubicin is 2460mg/m2）； The use of Chidamide is contraindicated; Impaired heart function or significant heart disease; Hepatitis B, hepatitis C active stage infection; Had undergone major surgery within 4 to 6 weeks prior or expected to undergo major surgery during the study; severe infection; Poorly controlled high blood pressure or diabetes; A history of active visceral bleeding within the previous 3 months A history of malignancy within five years; History of mental illness; A history of substance abuse or dependence; pregnant or lactating woman; The investigators did not consider it appropriate to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Mitoxantrone Hydrochloride Liposome Injection Combined With Chidamide<br> | Drug: Mitoxantrone liposome combine with Chidamide<br>* Mitoxantrone Hydrochloride Liposome Injection： Grade 1: 14mg/ m2, D1; Grade 2: 17mg/ m2, D1; Grade 3: 20mg/ m2, D1; Chidamide：20mg twice a week (D1 and D4 or D2 and D5 or D3 and D6) Every 28 days for a cycle, a maximum of 6 cycles of treatment. Mitoxantrone Hydrochloride Liposome Injection RP2D was determined in the phase I trial, and the combination regimen will be used to in the phase II study, with a cycle of every 28 days and a maximum of 6 cycles of treatment. Subsequently, maintenance treatment was performed: Chidamide, 20mg twice a week, for 1 year.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RP2D | Phase II recommended dose | 24 months | 
| ORR | Objective remission rate | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD | Maximum tolerated dose | 24 months | 
| DLT | Dose-limiting toxicity | 24 months | 
| DOR | Duration of remission time | 24 months |