Treatment for patients with aggressive non-Hodgkin's lymphoma

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 study is testing a new combination treatment for people with aggressive non-Hodgkin's lymphoma to see if it helps them feel better and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 115 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, chemotherapy, doxorubicin, rituximab
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT06244368 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the safety and efficacy of a treatment regimen combining mitoxantrone hydrochloride liposome with gemcitabine, vinorelbine, and/or anti-CD20 monoclonal antibodies in patients with relapsed or refractory aggressive non-Hodgkin lymphoma. It is a single-arm, open-label, multi-center study where participants will receive the treatment over a maximum of six 21-day cycles. The study aims to determine how well this combination therapy works in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with relapsed or refractory aggressive non-Hodgkin lymphoma who have not responded to at least one prior therapy.

Not a fit: Patients who are younger than 18 or older than 65, or those with non-aggressive forms of lymphoma, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with aggressive non-Hodgkin's lymphoma who have limited treatment choices.

How similar studies have performed: Other studies have shown promising results with similar treatment approaches in aggressive non-Hodgkin lymphoma, indicating potential for success.

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. -

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Wei Liu — Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC
• Study coordinator: Wei Liu

Conditions Peripheral T Cell Lymphoma; Diffuse Large B-cell Lymphoma; aggressive non-Hodgkin's lymphoma; Mitoxantrone hydrochloride liposome; GVM±R