Treatment for elderly patients with newly diagnosed diffuse large B-cell lymphoma

Prospective, Single-arm, Phase II Clinical Study of Rituximab, Lenalidomide, and Zanubrutinib Combination Regimen Followed by Immunochemotherapy in the Treatment of Elderly Patients With Newly-diagnosed Diffuse Large B-cell Lymphoma

This study is testing a new treatment plan for older patients with diffuse large B-cell lymphoma to see if a gentler approach helps them feel better and manage their cancer more effectively.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (estimated)
• Ages: 65 Years to 85 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, rituximab, zanubrutinib
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05290090 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to treat elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) using a combination regimen known as ZR2, which includes rituximab, lenalidomide, and zanubrutinib for two cycles. Following this, patients will receive up to four cycles of standard immunochemotherapy to reduce overall treatment intensity and improve their tolerance. The study focuses on addressing the unique challenges faced by older patients, such as comorbidities and poor performance status, which can hinder their ability to tolerate standard therapies. The goal is to enhance the patients' physical condition and long-term quality of life while effectively managing their lymphoma.

Who should consider this trial

Good fit: Ideal candidates are elderly patients aged 70-85 or those aged 65-70 with a poor performance status (ECOG score ≥2) who have newly diagnosed DLBCL.

Not a fit: Patients with prior anti-tumor therapies or those with serious hematopoietic dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and quality of life for elderly patients with DLBCL.

How similar studies have performed: While the combination of rituximab, lenalidomide, and BTK inhibitors has shown promise in other studies, this specific approach in elderly DLBCL patients is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Age: 70-85 years old, or 65-70 years old with ECOG score ≥2 points, both male and female.
3. Histopathologically confirmed as diffuse large B-cell lymphoma, not otherwise specified.
4. No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or biotherapy (tumor vaccine, cytokine, or anti-tumor growth factor).
5. 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).
6. Adequate organ and bone marrow function, no serious hematopoietic dysfunction, abnormal heart, lung, liver, kidney function and immune deficiency (no blood transfusion, granulocytic colony stimulating factor or other relevant medical support within 14 days prior to the use of the study drug) :

   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.
7. Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.
8. Negative serum pregnancy test and effective contraceptive use from signing informed consent until 6 months after the last chemotherapy.
9. Life expectancy \> 3 months.

Exclusion Criteria:

1. Pathological subtypes: primary central nervous system diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, 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
2. Hemophagocytic syndrome at the time of diagnosis.
3. Central nervous system involvement secondary to lymphoma.
4. Participating in other clinical studies.
5. 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).
6. 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.
7. Major surgery was performed within 28 days prior to study initiation.
8. Any active infection, including bacterial, fungal or viral infections, that requires systemic antiinfection therapy within 14 days prior to treatment.
9. 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.
10. History of stroke or intracranial hemorrhage within 6 months prior to first administration of the study drug.
11. History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past 12 months.
12. Patients who must take antiplatelet drugs and anticoagulants at the same time due to underlying diseases, and there is no alternative treatment plan.
13. Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is required. Patients were excluded if they had taken a CYP3A potent or moderate-acting inhibitor 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).
14. Hypersensitivity to the experimental drug is known.
15. 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, Hangzhou, China
• Study coordinator: xi chen

Conditions Diffuse Large B Cell Lymphoma; diffuse large B cell lymphoma; elderly; rituximab; lenalidomide; zanubrutinib; treatment; chemo-free