Treatment for relapsed or refractory diffuse large B-cell lymphoma using a combination of drugs

The Efficiency and Safety of Zanubrutinib in Combination With Polatuzumab Vedotin, Bendamustine and Rituximab in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma: a Prospective, Single-arm, Multicenter Study

This study is testing a new combination of drugs to see if it can help people aged 18 to 75 with relapsed or refractory diffuse large B-cell lymphoma feel better and improve their chances of recovery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: chemotherapy, Polatuzumab, rituximab, Zanubrutinib
• Locations: 1 site (Hanzhou, Zhejiang)
• Trial ID: NCT06554600 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial investigates the efficacy and safety of a combination therapy involving Zanubrutinib, Polatuzumab Vedotin, Bendamustine, and Rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Participants aged 18 to 75 will receive four courses of the Polo-ZBR regimen, followed by consolidation therapy for those who achieve a partial or complete response. After consolidation, patients will receive maintenance therapy with Zanubrutinib for one year, with follow-up lasting up to two years post-enrollment. The study aims to determine the effectiveness of this treatment approach in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with relapsed or refractory diffuse large B-cell lymphoma who have measurable lesions and meet specific inclusion criteria.

Not a fit: Patients who have not been diagnosed with DLBCL or those who have not experienced relapse or refractory disease after initial treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed or refractory DLBCL.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating DLBCL, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Aged between 18 and 75 (inclusive);
* For patients with DLBCL confirmed by histopathology (which needs to be confirmed by specimens after this or past recurrence), the following DLBCL histology will be considered eligible for study enrollment:

DLBCL, NOS(includes GCB type and ABC type); T-cell rich large B-cell lymphoma; High-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement; High-grade B-cell lymphoma, NOS; Primary mediastinal (thymus) large B-cell lymphoma; EB virus positive DLBCL, NOS;HHV-8 positive DLBCL, NOS;

* Relapsed refractory patients, defined as those who had no response after first-line treatment (including immunochemotherapy, chemotherapy or hematopoietic stem cell transplantation) or relapsed or refractory after remission;
* There is at least one two-dimensional measurable lesion with a short diameter ≥1.0cm;
* Estimated survival time ≥3 months;
* The patient is informed and agrees to the program;
* ECOG score 0-2 points;
* Those who understand the procedure and content of the experiment, voluntarily participate in the study and sign the informed consent;
* Patients can follow up on schedule, communicate well with researchers and complete the trial according to the trial regulations;
* Confirm negative pregnancy test of female patients of childbearing age within 7 days before administration; Women and men in the reproductive period must agree to use medically recognized effective contraception throughout the treatment period and for 6 months after the end of the trial.

Exclusion Criteria:

* Active bleeding within 4 weeks prior to initial administration or anticoagulant therapy such as warfarin or vitamin K antagonists during the study period, or a tendency to bleed (such as esophageal varicose veins at risk of bleeding, locally active ulcerative lesions) or a clotting disorder deemed by the investigator;
* Surgical procedures have been performed within 6 weeks prior to the signing of the informed consent for the first dose of the trial drug, but tests for diagnostic purposes are not considered surgical procedures, and the insertion of a vascular access device will be exempt from this exclusion criteria;
* History of stroke and intracranial hemorrhage within 6 months before the first administration, except intracranial hemorrhage after surgery;
* Those who cannot stop or adjust moderate or strong CYP3A inhibitors;
* Have received organ transplantation or allogeneic stem cell transplantation;
* Previous or concurrent history of other malignant tumors;
* Chronic or currently active infectious diseases requiring systemic antibiotic, antifungal, or antiviral treatment (except EBV infections);
* Accompanied by uncontrolled cardiovascular and cerebrovascular diseases, thrombotic diseases, connective tissue diseases and other diseases. Those who were not considered suitable for inclusion by the researchers;
* Laboratory test value at screening (unless due to lymphoma) : Leukocyte count \< 3.5×109/L, neutrophils \<1.5×109/L, platelets \<80×109/L, hemoglobin \<100g/L, ALT or AST were 2.5 times higher than the upper limit of normal, bilirubin was 1.5 times higher than the upper limit of normal, creatinine level was 1.5 times higher than the upper limit of normal;
* HbsAg positive patients need to check HBV-DNA \< 104 to be enrolled. In addition, if HBsAg is negative but HBcAb is positive (regardless of HBsAb status), HBV-DNA testing is also required, and HBV-DNA results \< 104 are required to be enrolled and continue treatment and monitoring of HBV-DNA. Patients with HCV antibody positive were required to check HCV-RNA quantitative DNA \< 103 to be enrolled;
* HIV antibody, treponema pallidum antibody positive;
* Pregnant or lactating women;
* Those who have a history of drug use or drug abuse upon inquiry;
* Patient communication, understanding and cooperation are not enough, or compliance is poor, and it cannot be guaranteed that the program is carried out according to the requirements;
* Known allergy to the investigational drug or its related ingredients;
* Patients with past or current lymphoma central invasion;
* The patient is unable to swallow the capsule or has a disease or condition that severely affects gastrointestinal function, such as malabsorption syndrome, removal of the stomach or small intestine, or complete intestinal obstruction;
* Patients who could not stop using any other antitumor drugs within 2 weeks prior to medication in this study;
* Participants considered unsuitable for this clinical trial due to various other reasons.

Where this trial is running

Hanzhou, Zhejiang

• 2nd Affiliated Hospital, School of Medicine, Zhejiang University — Hanzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Xianggui Yuan

Conditions Refractory or Relapsed Diffuse Large B Cell Lymphoma