A Single-arm, Multicenter, Prospective Clinical Study of Mitoxantrone Liposome Combined With Chidamide and Azacitidine in the Treatment of Relapsed and Refractory Peripheral T-cell Lymphoma

A Single-arm, Multicenter, Prospective Clinical Study of Mitoxantrone Hydrochloride Liposome Injection Combined With Chidamide and Azacitidine in the Treatment of Relapsed and Refractory Peripheral T-cell Lymphoma

To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection combined with chidamide and azacitidine in the treatment of relapsed and refractory peripheral T-cell lymphoma

Study Overview

• Status: Recruiting
• Conditions: Peripheral T Cell Lymphoma
• Intervention / Treatment: Drug: Mitoxantrone liposome、Chidamide、Azacitidine

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xibin Xiao; Phone Number: 13858015535; Email: xiaoxibinzju@zju.edu.cn
• Study Contact Backup: Name: Wenbin Qian; Phone Number: 13605801032

Study Locations

• China
  • Zhejiang
    • Zhejiang, Zhejiang, China
      • Recruiting
      • Second Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Xibin Xiao; Phone Number: 13858015535; Email: xiaoxibinzju@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients fully understand this study, voluntarily participate in and sign an informed consent form (ICF);
2. Age: 18~75 years old;
3. Expected survival time ≥ 3 months;
4. Histopathologically confirmed PTCL, one of the following subtypes:

(1) Peripheral T-cell lymphoma unspecified (PTCL-NOS) (2) Angioimmunoblastic T-cell lymphoma (AITL) (3) Anaplastic large T-cell lymphoma (ALCL), ALK+ (4) Anaplastic large T-cell lymphoma (ALCL), ALK- (5) Other subtypes of PTCL that the researchers believe can be enrolled; 5. Relapsed/refractory patients who have received at least first-line systemic therapy with anthracycline-containing regimens in the past. Relapse was defined as relapse after CR or progression after PR; refractory was defined as previous systemic chemotherapy treatment, 2 cycles of response evaluation as PD, or 4 cycles of response evaluation as SD; 6. There must be at least one evaluable or measurable lesion that meets the Lugano2014 criteria: lymph node lesions, measurable lymph nodes should be >1.5cm in length; non-lymph node lesions, measurable extranodal lesions should be >1.0cm in length; 7. ECOG score 0-2 points; 8. Bone marrow function: neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, hemoglobin ≥80g/L (the neutrophil count in patients with bone marrow involvement can be relaxed to ≥1.0×109/L, Platelet count can be relaxed to ≥50×109/L, and hemoglobin can be relaxed to ≥75 g/L); Liver and kidney function: Serum creatinine ≤1.5 times the upper limit of normal; AST and ALT ≤2.5 times the upper limit of normal (for patients with liver involvement ≤5 times the upper limit of normal); total bilirubin ≤1.5 times the upper limit of normal (for liver involvement patients ≤ 3 times the upper limit of normal);

Exclusion Criteria:

1. The subject's previous history of anti-tumor therapy meets one of the following conditions:

   1. Those who have received mitoxantrone or mitoxantrone liposome in the past;
   2. Have received doxorubicin or other anthracycline therapy in the past, and the total cumulative dose of doxorubicin is more than 360 mg/m2 (1 mg doxorubicin equivalent to 2 mg epirubicin converted from other anthracyclines);
   3. Patients who have received autologous hematopoietic stem cell transplantation within 100 days of the first medication, or have received allogeneic hematopoietic stem cell transplantation;
   4. Received anti-tumor therapy (including chemotherapy, targeted therapy, hormone therapy, taking traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received clinical trial drugs within 4 weeks before the first use of the study drug;
2. Hypersensitivity to any study drug or its components;
3. Uncontrollable systemic diseases (such as advanced infection, uncontrollable hypertension, diabetes, etc.);

4. Cardiac function and disease meet one of the following conditions:

   1. Long QTc syndrome or QTc interval >480 ms;
   2. Complete left bundle branch block, second or third degree atrioventricular block;
   3. severe, uncontrolled arrhythmia requiring medical treatment;
   4. New York College of Cardiology classification ≥ grade III;
   5. Cardiac ejection fraction (LVEF) less than 50%;
   6. History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia, or any other arrhythmia requiring treatment, clinically significant pericardial disease within 6 months prior to recruitment, or acute ischemic or active ECG evidence of conduction system abnormalities.
5. Active infection of hepatitis B and C (HBV surface antigen positive and hepatitis B virus DNA more than 1x103 copies/mL; hepatitis C virus RNA more than 1x103 copies/mL);
6. Human immunodeficiency virus (HIV) infection (HIV antibody positive);
7. Past or present with other malignant tumors (except for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ, and other malignant tumors that have been effectively controlled without treatment within the past five years);
8. Suffering from primary or secondary central nervous system (CNS) lymphoma or a history of CNS lymphoma at the time of recruitment;
9. There are obvious gastrointestinal diseases at the time of screening, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
10. Pregnant, lactating women and patients of childbearing age who are unwilling to take contraceptive measures;
11. Subjects with lymphoma and leukemia (proportion of malignant tumor cells in bone marrow examination> 20%) Circumstances judged by other investigators to be inappropriate 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 liposome combined with Chidamide and Azacitidine	Drug: Mitoxantrone liposome、Chidamide、Azacitidine; Mitoxantrone liposome 20mg/m2, d1; Chidamide 20mg, biw; Azacitidine 100mg, d1~7; Every 4 weeks is a cycle, with a maximum of 4 cycles of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	objective response rate	one year

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Ningbo No. 1 Hospital; Jinhua Central Hospital; Huizhou Municipal Central Hospital
• Investigators: Principal Investigator: Wenbin Qian, 13605801032

Study record dates

Study Major Dates

• Study Start (Anticipated): August 11, 2022
• Primary Completion (Anticipated): August 11, 2023
• Study Completion (Anticipated): August 11, 2024

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 9, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 9, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Relapsed and refractory peripheral T-cell lymphoma; mitoxantrone liposomes
• 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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Azacitidine; Mitoxantrone
• Other Study ID Numbers: 2022-0453

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No