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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Overall Response Rate (ORR) [Срок оценки: up to 2 years]

Вторичные конечные точки (4)

• Complete Response Rate (CRR) [Срок оценки: up to 2 years]
• Progression-Free-Survival (PFS) [Срок оценки: up to 2 years]
• Overall survival (OS) [Срок оценки: up to 2 years]
• Incidence of Treatment-Emergent Adverse Events [Срок оценки: up to 2 years]

Критерии участия

Критерии включения

• Age ≥18, ≤65 years.
• Expected survival ≥ 3 months.
• 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.
• 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;
• Eastern Cooperative Oncology Group (ECOG) : 0-2
• 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).
• 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.-

Критерии исключения

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

• Subjects who have been treated with mitoxantrone or mitoxantrone liposomes;
• 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);
• 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;
• Subjects who received autologous hematopoietic stem cell transplantation or allogeneic hematopoietic stem cell transplantation within 100 days before the first administration of study drugs;
• Subjects who received chimeric antigen receptor T-cell (CAR-T) therapy.
• Hypersensitivity to any study drug or its components.
• Uncontrolled systemic diseases (such as active infection, uncontrolled hypertension, diabetes, etc.)
• Heart function and disease meet one of the following conditions:

• Long QTc syndrome or QTc interval > 480 ms;
• Complete left bundle branch block, grade II or III atrioventricular block;
• Serious and uncontrolled arrhythmias requiring drug treatment;
• New York Heart Association grade ≥ III;
• Left Ventricular Ejection Fractions (LVEF)< 50%;
• 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.
• 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).
• Human immunodeficiency virus (HIV) infection (defined as HIV antibody positive).
• 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.
• Pregnant and lactating women and patients of childbearing age who are unwilling to take contraceptive measures.
• ≥ Grade 3 neuritis.
• Active central nervous system (CNS) lymphoma;
• Unsuitable subjects for this study determined by the investigator. -

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC — Тяньцзинь

Идентификаторы

NCT: NCT06244368 · IIT2023065

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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