Combination treatment for relapsed or refractory diffuse large B-cell lymphoma

A Prospective, Single Arm, Open Label Study to Evaluate the Safety and Efficacy of Zanubrutinib, Lenalidomide With R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma.

This study is testing a new combination treatment for people with relapsed or stubborn diffuse large B-cell lymphoma to see if it helps them when other treatments haven't worked.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: RenJi Hospital (Academic / other)
• Drugs / interventions: chemotherapy, Rituximab, zanubrutinib
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT06033820 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a combination therapy involving zanubrutinib, lenalidomide, and Rituximab-ICE in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). It is a prospective, single-center, open-label study that aims to provide a new treatment option for patients who have not responded to previous therapies. Participants will be monitored for their response to the treatment based on measurable disease criteria. The study focuses on patients who have already undergone at least one systemic treatment regimen for DLBCL.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed DLBCL who have experienced relapsed or refractory disease after prior treatments.

Not a fit: Patients who have not received any prior systemic therapy for DLBCL or those with non-CD20 positive tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with difficult-to-treat DLBCL.

How similar studies have performed: While this specific combination has not been widely tested, similar approaches using targeted therapies in DLBCL have shown promising results in other studies.

Eligibility criteria

Inclusion Criteria:

1. Age between 18 years and 75 years 2. Histologically confirmed diagnosis of DLBCL, CD20 positive 3. Patients received at least one systemic regimens for the treatment of DLBCL, and one therapy line must have included a CD20-targeted therapy.

4. Relapsed or refractory disease 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 6. Measurable disease on cross section imaging by PET and/or CT that is at least 1.5 cm in the longest diameter and measurable in two perpendicular dimensions as defined by IWG criteria.

7. Patients must meet the following laboratory criteria at screening, including:

1. Absolute neutrophil count (ANC) ≥1.5 x 109/L or ≥0.75 x 109/L if bone marrow involvement
2. Platelets ≥90 x 109/L or ≥50 x 109/L if bone marrow involvement
3. Hemoglobin ≥75 g/dL or ≥50 g/dL if bone marrow involvement
4. Total bilirubin ≤2.5 x upper limit of normal (ULN) unless bilirubin rise is due to Gilbert's syndrome or of hepatic involvement.
5. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤3 x (ULN) or \< 5 x ULN if hepatic involvement.
6. Creatinine Clearance Rate ≥60 mL/min.
7. INR ≤1.5 x ULN and aPTT ≤1.5 x ULN 8. Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[β-hCG\]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study. Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. For females, these restrictions apply for 3 month after the last dose of study drug.

9. Male subject agrees to use an acceptable method for contraception for the duration of the study. Men must agree to not donate sperm during and after the study. For males, these restrictions apply for 3 months after the last dose of study drug.

10. Sign an informed consent document indicating that they understand the purpose of and procedures required for the study, and are willing to participate in the study. Must be able to adhere to study visit schedules and other protocol requirements.

Exclusion Criteria:

1. Patients who have a history of "double/triple hit" genetics. 2. Patients who have, within 14 days prior to Day 1 dosing:

1. not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy.
2. undergone major surgery or suffered from significant traumatic injury.
3. received live vaccines.
4. required parenteral antimicrobial therapy for active, intercurrent infections. 3. Patients who have use investigational agents within the period ≤ 3 months prior to Day 1 dosing.

4. Patients who have,

1. Adverse events (AEs) due to previous anti-tumor therapy have not recovered
2. Known allergy or sensitivity to any drug contained in the regimen
3. have undergone ASCT within the period ≤3 months prior to signing the informed consent form.
4. have undergone previous allogenic stem cell transplantation.
5. have a history of deep venous thrombosis/embolism and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period.
6. concurrently use other anticancer or experimental treatments. 5. Coexistent second malignancy or history of prior malignancy within previous 5 years.

6. Patients who have,

1. Known history of active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
2. Known history of human immunodeficiency virus (HIV) infection.
3. Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures.
4. History of gastrointestinal disorder or defect that would interfere with the absorption of the study drug.
5. Patients with history of severe hemorrhagic disorders.
6. History of stroke or intracranial hemorrhage within 6 months prior to registration

Where this trial is running

Shanghai, Shanghai

• Renji Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Hong-Hui Huang, Professor

Conditions Diffuse Large B-cell Lymphoma Recurrent; Diffuse Large B Cell Lymphoma Refractory; diffuse large B-cell lymphoma; Zanubrutinib; Lenalidomide; Salvage therapy