Treatment for early relapsed or refractory diffuse large B-cell lymphoma

Prospective, Single-center, Phase II Clinical Study of Anlotinib in Combination With Rituximab，Gemcitabine and Oxaliplatin (A-RGEMOX) in the Treatment of Early Relapsed/Refractory Diffuse Large B-cell Lymphoma

This study is testing a new combination treatment for people with early relapsed or hard-to-treat diffuse large B-cell lymphoma to see if it can help them feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (other)
• Drugs / interventions: rituximab, chemotherapy, anlotinib
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06086197 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of a combination treatment involving anlotinib, rituximab, gemcitabine, and oxaliplatin (A-RGEMOX) for patients with early relapsed or refractory diffuse large B-cell lymphoma (DLBCL). DLBCL is an aggressive form of lymphoma with a poor prognosis for those who experience early relapse or are refractory to initial treatments. The study aims to improve response rates and long-term survival for this high-risk patient population. Participants will be monitored for their response to the treatment and overall health outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histopathologically confirmed DLBCL who have experienced early relapse or are refractory to first-line treatment.

Not a fit: Patients who have not received first-line treatment or those with other types of lymphoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates for patients with early relapsed or refractory DLBCL.

How similar studies have performed: Previous studies have indicated potential benefits of targeting angiogenesis in lymphoma treatment, suggesting this approach may be promising.

Eligibility 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.

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Principal investigator: Haiyan Yang — Zhejiang Cancer Hospital
• Study coordinator: Xi Chen

Conditions: Diffuse Large B-cell Lymphoma Recurrent, Diffuse Large B Cell Lymphoma Refractory, angiogenesis, anlotinib, early relapse, treatment