GVM±R in Patients With Relapsed or Refractory Aggressive NHL.

A Single Arm, Open Label, Multi-center Study of Mitoxantrone Hydrochloride Liposome, Gemcitabine, Vinorelbine With or Without Anti-CD20 Monoclonal Antibody (GVM±R) in Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

This is a prospective clinical study to evaluate the safety and efficacy of GVM±R in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL).

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-cell Lymphoma; Peripheral T Cell Lymphoma
• Intervention / Treatment: Drug: GVM±R regimen

Detailed Description

This is a single-arm, open label, multi-center clinical study to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in combination with gemcitabine, vinorelbine and/or anti-CD20 monoclonal antibody(GVM ± R) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL).Mitoxantrone hydrochloride liposome will be given on day 1 at dose of 18 mg/m2 and be combined with gemcitabine, vinorelbine and/or rituximab (Pts with CD20-positive lymphomas are evaluated by the investigator on whether to combine rituximab or choose another CD20 monoclonal antibody).Each cycle consists of 21 days. A maximum of 6 cycles of therapy are planned.

• Study Type: Interventional
• Enrollment (Estimated): 115
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wei Liu; Phone Number: 022-23608461; Email: liuwei@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC
      • Principal Investigator: Wei Liu
      • Contact: Wei Liu; Email: liuwei@ihcams.ac.cn
      • Contact: Email: liuwei@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18, ≤65 years.
2. Expected survival ≥ 3 months.
3. Subjects with aggressive NHL who have relapsed or proven refractory to at least one line of standard therapy or have achieved PR as the best response after a minimum of 4 cycles of therapy (patients with a Deauville score of 4 must have biopsy-proven residual disease). Relapse is defined as a disease response (PR/CR) to the last-line therapy with a duration of response exceeding 6 months. Refractory disease can be confirmed under any of the following conditions: 1) no partial or complete response to the last-line therapy; 2) the duration of complete or partial response to the last-line therapy is no longer than 6 months from the last dose of therapy; 3) Recurrence after hematopoietic stem cell transplantation.
4. Subjects must have at least one measurable lesion per lugano2014 criteria: for lymph node lesions, the long diameter should be > 1.5cm; For non-lymph node lesions, the long diameter should be > 1.0cm;
5. Eastern Cooperative Oncology Group (ECOG) : 0-2
6. Peripheral blood: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count (PLT) ≥75×109/L, Hemoglobin(HB)≥ 80g/L.(Restriction may be relaxed in patients with bone marrow involvement, Absolute neutrophil count (ANC) ≥1.0×109/L, Platelet count (PLT) ≥50×109/L, Hemoglobin(HB)≥ 75g/L).
7. Liver and kidney function: Serum creatinine (Scr) ≤1.5X upper limit of normal (ULN).Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5X ULN, Total bilirubin (TBIL) ≤1.5X upper limit of normal (ULN).(If the lymphoma involves the liver, TBIL≤3 X ULN.AST and ALT≤5 X ULN). For Pts diagnosed with Gilbert's disease, TBIL was enrolled if it was ≤3 X ULN.-

Exclusion Criteria:

1. The subject had previously received any of the following anti-tumor treatments:

   1. Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;
   2. Previously received doxorubicin or other anthracycline treatment, and the total cumulative dose of doxorubicin was more than 360 mg/m2 (For other anthracyclines, 1 mg doxorubicin equivalent to 2 mg epirubicin);
   3. Subjects who received anti-tumor treatment (including chemotherapy, targeted therapy, glucocorticoid, traditional Chinese medicine with anti-tumor activity, etc.) or participated in other clinical trials and received trial drugs within 4 weeks or 5 half-lives((whichever comes first) before the first administration of the study drugs;
   4. Subjects who received autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation within 100 days before the first administration of study drugs;
   5. Subjects who received chimeric antigen receptor T-cell (CAR-T) therapy.
2. Hypersensitivity to any study drug or its components.
3. Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.)

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

   1. Long QTc syndrome or QTc interval > 480 ms;
   2. Complete left bundle branch block, grade II or III atrioventricular block;
   3. Serious and uncontrolled arrhythmias requiring drug treatment;
   4. New York Heart Association grade ≥ III;
   5. Left Ventricular Ejection Fractions (LVEF)< 50%;
   6. A history of myocardial infarction, unstable angina pectoris, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, a history of clinically serious pericardial disease, or ECG evidence of acute ischemia or active conduction system abnormalities within 6 months before recruitment.
5. Active hepatitis B and C infection (defined as hepatitis B virus surface antigen positive and hepatitis B virus DNA higher than the Upper limit of normal(ULN); Hepatitis C virus antibody positive and hepatitis C virus RNA higher than the Upper limit of normal).
6. Human immunodeficiency virus (HIV) infection (defined as HIV antibody positive).
7. Patients with other malignant tumors, except for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervical carcinoma in situ or other tumors without treatment during the past 5 years.
8. Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures.
9. ≥ Grade 3 neuritis.
10. Active central nervous system (CNS) lymphoma;
11. Unsuitable subjects for this study determined by the investigator. -

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: GVM±R; Patients with relapsed or refractory aggressive NHL will undergo GVM±R therapy	Drug: GVM±R regimen; Mitoxantrone hydrochloride liposome (18 mg/m^2) on day 1； Gemcitabine (800 mg/m^2) on day 1,8； Vinorelbine (20mg/m^2) on day 1,8； Rituximab (375mg/m^2) on day 1; The regimen will be administered every 3 weeks, for a maximum of 6 cycles. The choice of CD20 monoclonal antibody will be determined by the attending physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Response is assessed according to the lugano criteria	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate (CRR)	Response is assessed according to the lugano criteria	up to 2 years
Progression-Free-Survival (PFS)	From the date of the first dose of therapy is given until disease progression, death or last follow-up	up to 2 years
Overall survival (OS)	From the date of inclusion to date of death, irrespective of cause	up to 2 years
Incidence of Treatment-Emergent Adverse Events	The adverse events were evaluated by NCI-CTCAE 5.0 standard Hematologic and non-hematologic toxicity	up to 2 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Collaborators: The First Affiliated Hospital of Nanchang University; Peking University Third Hospital; Shengjing Hospital; Xuanwu Hospital, Beijing; Beijing Tongren Hospital; China-Japan Friendship Hospital; The First Hospital of Jilin University; Hebei Medical University Fourth Hospital; Affiliated Cancer Hospital & Institute of Guangzhou Medical University; First Hospital of China Medical University; The Second Affiliated Hospital of Harbin Medical University; The First Affiliated Hospital of Dalian Medical University; First Affiliated Hospital of Harbin Medical University; The Second Affiliated Hospital of Kunming Medical University; The Affiliated Ganzhou Hospital of Nanchang University; Chengdu Shangjin Nanfu Hospital; People's Hospital of Zhengzhou University; The First Affiliated Hospital of Bengbu Medical University
• Investigators: Principal Investigator: Hongmei Jing, Peking University Third Hospital; Principal Investigator: Zeping Zhou, The Second Affiliated Hospital of Kunming Medical University; Principal Investigator: Wei Liu, Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC; Principal Investigator: Xiaojing Yan, First Hospital of China Medical University; Principal Investigator: HaiSheng、Chen Liu 、Huang, Hebei Medical University Fourth Hospital; Principal Investigator: Yongqian Jia, Chengdu Shangjin Nanfu Hospital; Principal Investigator: Yunhong Huang, Affiliated Cancer Hospital & Institute of Guizhou Medical University; Principal Investigator: Xiaobo Wang, The Second Affiliated Hospital of Dalian Medical University; Principal Investigator: Wanling Sun, Xuanwu Hospital, Beijing; Principal Investigator: Mingxing Zhong, The Affiliated Ganzhou Hospital of Nanchang University; Principal Investigator: Liang Wang, Beijing Tongren Hospital; Principal Investigator: Xiuli Sun, The First Affiliated Hospital of Dalian Medical University; Principal Investigator: Ou Bai, The First Hospital of Jilin University; Principal Investigator: Shuxia Guo, People's Hospital of Zhengzhou University; Principal Investigator: Yanli Yang, The First Affiliated Hospital of Bengbu Medical University; Principal Investigator: Fei Li, The First Affiliated Hospital of Nanchang University; Principal Investigator: Aichun Liu, The Second Affiliated Hospital of Harbin Medical University; Principal Investigator: Aijun Liao, Shengjing Hospital; Principal Investigator: Shuye Wang, First Affiliated Hospital of Harbin Medical University; Principal Investigator: Zhenling Li, China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2024
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: January 28, 2024
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: GVM±R; aggressive non-Hodgkin's lymphoma (NHL); Mitoxantrone hydrochloride liposome
• Additional Relevant MeSH Terms: Aberrant Motor Behavior in Dementia; Neoplasms; Immune System Diseases; Behavioral Symptoms; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, T-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell, Peripheral; Aggression
• Other Study ID Numbers: IIT2023065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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