Clinical trial NCT06244368: GVM±R in Patients With Relapsed or Refractory Aggressive NHL.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Peripheral T Cell Lymphoma
Diffuse Large B-cell Lymphoma
Keywords: aggressive non-Hodgkin's lymphoma (NHL)
Mitoxantrone hydrochloride liposome
GVM±R
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: First Hospital of China Medical University
name: Hebei Medical University Fourth Hospital
name: Chengdu Shangjin Nanfu Hospital
name: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
name: Xuanwu Hospital, Beijing
name: The Affiliated Ganzhou Hospital of Nanchang University
name: Beijing Tongren Hospital
name: The First Affiliated Hospital of Dalian Medical University
name: The First Hospital of Jilin University
name: People's Hospital of Zhengzhou University
name: The First Affiliated Hospital of Bengbu Medical University
name: The Second Affiliated Hospital of Kunming Medical University
name: The First Affiliated Hospital of Nanchang University
name: The Second Affiliated Hospital of Harbin Medical University
name: Shengjing Hospital
name: Peking University Third Hospital
name: First Affiliated Hospital of Harbin Medical University
name: China-Japan Friendship Hospital
First posted: 2024-02-06
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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. -

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: up to 2 years
Secondary outcomes:
measure: Complete Response Rate (CRR)
timeFrame: up to 2 years
measure: Progression-Free-Survival (PFS)
timeFrame: up to 2 years
measure: Overall survival (OS)
timeFrame: up to 2 years
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC
name: Wei Liu
role: PRINCIPAL_INVESTIGATOR
affiliation: First Hospital of China Medical University
name: Xiaojing Yan
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebei Medical University Fourth Hospital
name: HaiSheng、Chen Liu 、Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: Chengdu Shangjin Nanfu Hospital
name: Yongqian Jia
role: PRINCIPAL_INVESTIGATOR
affiliation: Affiliated Cancer Hospital & Institute of Guizhou Medical University
name: Yunhong Huang
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of Dalian Medical University
name: Xiaobo Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: Xuanwu Hospital, Beijing
name: Wanling Sun
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Ganzhou Hospital of Nanchang University
name: Mingxing Zhong
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tongren Hospital
name: Liang Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Dalian Medical University
name: Xiuli Sun
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Hospital of Jilin University
name: Ou Bai
role: PRINCIPAL_INVESTIGATOR
affiliation: People's Hospital of Zhengzhou University
name: Shuxia Guo
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Bengbu Medical University
name: Yanli Yang
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of Kunming Medical University
name: Zeping Zhou
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Nanchang University
name: Fei Li
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of Harbin Medical University
name: Aichun Liu
role: PRINCIPAL_INVESTIGATOR
affiliation: Shengjing Hospital
name: Aijun Liao
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Third Hospital
name: Hongmei Jing
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Harbin Medical University
name: Shuye Wang
role: PRINCIPAL_INVESTIGATOR
affiliation: China-Japan Friendship Hospital
name: Zhenling Li
role: PRINCIPAL_INVESTIGATOR
References: