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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed and Refractory Peripheral T-cell Lymphoma
• Intervention / Treatment: Drug: Mitoxantrone liposome combine with Chidamide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Li Zhiming, M.D.; Phone Number: 020-87343292; Email: Lizhm@sysucc.org.cn
• Study Contact Backup: Name: Li Zhiming, M.D.; Phone Number: 02087343292; Email: Lizhm@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Department of Medical Oncology,Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Mitoxantrone Hydrochloride Liposome Injection Combined With Chidamide

Drug: Mitoxantrone liposome combine with Chidamide; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: September 1, 2022
• First Posted (Actual): September 2, 2022

Study Record Updates

• Last Update Posted (Actual): September 2, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Mitoxantrone
• Other Study ID Numbers: 2022-FXY-140-内科

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No