A-RGEMOX in the Treatment of Early Relapsed/Refractory DLBCL

• Status: Recruiting
• Trial end date: 2026-10-01
• Target enrollment: 0
• Participant gender: All

Summary

As the most common subtype of lymphoma, diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy. However, patients with early relapse (relapse within 12 months since diagnosis or the end of first-line treatment, ER) or primary refractory had an even worse prognosis. Thus, the investigators plan to evaluate the efficacy and safety of anlotinib combined with rituximab, gemcitabine, oxaliplatin (A-RGEMOX) in the treatment of early relapsed/refractory diffuse large B-cell lymphoma.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhejiang Cancer Hospital
• Treatments: Gemcitabine; Oxaliplatin; Rituximab

Criteria

Inclusion Criteria:

• Participate in the clinical study voluntarily: fully understand and be informed of the study and sign the informed consent in person; Willing to follow and be able to complete all test procedures.

• Age≥18 years old, ECOG score ≥2 points, both male and female.

• Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified; high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement; high-grade B-cell lymphoma, not otherwise specified; EBV positive diffuse large B-cell lymphoma

• Must meet one of the following conditions:

1. Early relapse: response (≥PR) to first-line systemic therapy (including rituximab and anthracyclines) and disease progression within 12 months after the end of treatment;

2. Refractory: first-line treatment includes rituximab and anthracyclines, and no response has been achieved with the most recent systemic treatment (≥PR).

• At least one evaluable or measurable lesion that meets Lugano2014 criteria (evaluable lesion: PET/CT examination showing increased uptake in lymph nodes or extranodal areas (higher than liver) and PET/CT and/or CT consistent with lymphoma; Measurable lesions: nodular lesions >15mm in length or extragendal lesions >10mm in length with increased FDG uptake).

• Adequate organ and bone marrow function, no serious hematopoietic dysfunction, abnormal heart, lung, liver, kidney function and immune deficiency:

1. Neutrophil absolute count (ANC) ≥1.5×109/L (1500/mm3), platelet ≥75×109/L, hemoglobin ≥100g/L (if bone marrow is involved, platelet ≥50×109/L, ANC ≥1.0×109/L, hemoglobin ≥80g/L).

2. Liver function: serum bilirubin ≤2.5 times the upper limit of normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the upper limit of normal value (AST or ALT≤5 times the upper limit of normal value is allowed if liver is involved).

3. Renal function: creatinine clearance ≥60 mL/min (estimated according to the Cockcroft-Gault formula).

4. Coagulation function: INR≤1.5 times the upper limit of normal value; PT and APTT≤1.5 times the upper limit of normal value.

• Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.

• Negative serum pregnancy test and effective contraceptive use from signing informed consent until 6 months after the last chemotherapy.

• Life expectancy > 3 months.

Exclusion Criteria:

• Pathological subtypes: primary central nervous system diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma.

• Hemophagocytic syndrome at the time of diagnosis.

• Central nervous system involvement secondary to lymphoma.

• Participating in other clinical studies, or the first study drug is administered less than 4 weeks after the end of treatment in the previous clinical study.

• Medical history of other active malignancy within 2 years prior to enrollment, except for the following conditions:(1) adequately treated in situ of the cervix carcinoma; (2) local basal cell carcinoma or squamous cell carcinoma of skin; (3) Pre-existing malignant disease that is under control and has undergone local radical treatment (surgical or other forms).

• History of Human Immunodeficiency Virus (HIV) infection and/or acquired Immunodeficiency syndrome. Patients with positive hepatitis B surface antigen or hepatitis C virus antibody must be tested hepatitis B virus DNA (no more than 1000 iu/ml) and HCV RNA detection (below the detection limit). Patients with hepatitis B virus carriers, or stabilized hepatitis B with anti-virus treatment and cured hepatitis C can be included.

• Major surgery was performed within 28 days prior to study initiation.

• Any active infection, including bacterial, fungal or viral infections, that requires systemic antiinfection therapy within 14 days prior to treatment.

• Accompanied with severe or uncontrolled disease, including symptomatic of congestive heart failure, uncontrolled hypertension, unstable angina, active peptic ulcer or A history of severe hemorrhagic diseases, such as hemophilia A, hemophilia B, von willebrand disease or blood transfusion or other medical intervention history of spontaneous bleeding.

• History of stroke or intracranial hemorrhage within 6 months prior to first administration of the study drug.

• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months.

• Patients who must take antiplatelet drugs and anticoagulants at the same time due to underlying diseases, and there is no alternative treatment plan.

• Continuous treatment with strong CYP1A2 and CYP3A inhibitors or inducers is required. Patients were excluded if they had taken a strong CYP1A2 and CYP3A inhibitors or inducer within 7 days prior to the first administration of the study drug (or had taken these drugs for less than 5 half-lives).

• Hypersensitivity to the experimental drug is known.

• Patients deemed unsuitable for the study by researchers.