R-MINI-CHOP versus R-MINI-CHP in combination with polatuzumab-vedotin, as primary treatment for patients with diffuse large B-cell lymphoma, ≥80 years, or frail ≥75 years – an open label randomized Nordic Lymphoma Group phase III trial - NLG-LBC7 (POLAR BEAR)

The primary objective of this study is to evaluate the **efficacy** of pola-R-mini-CHP compared to R-mini-CHOP as a primary treatment for patients with **Diffuse Large B-Cell Lymphoma** who are aged 80 years or older, or who are frail and aged 75 years or older. This comparison is clinically relevant as it aims to determine the most effective treatment regimen for this specific patient population, potentially improving therapeutic outcomes and guiding clinical decision-making.

Secondary objectives include:

• Assessing efficacy through the evaluation of response duration, complete remission rate (CR), overall response rate (ORR), health-related quality of life (HRQOL), lymphoma-specific survival (LSS), and overall survival (OS).
• Evaluating safety by collecting data on adverse events and serious adverse events.
• Assessing health-related quality of life using the EORTC QLQ-C30 questionnaire.

The clinical trial involves a total of **50 participants** diagnosed with **Diffuse Large B-Cell Lymphoma**. The study population includes both male and female subjects, with an age range starting from 80 years or frail individuals aged 75 years and above, as determined by a simplified comprehensive geriatric assessment. Participants were selected based on specific criteria, including histologically confirmed lymphoma of certain subtypes, stage II-IV disease, and a WHO performance status of 0 to 3, provided it is related to the lymphoma. The trial does not include a vulnerable population. Participants have not received previous treatment for lymphoma and have at least one measurable site of disease. Lifestyle factors such as diet and physical activity are not specified in the data provided. The selection process ensures that all participants have given written informed consent to partake in the study.

The clinical trial is designed to evaluate the efficacy of **pola-R-mini-CHP** compared to R-mini-CHOP as a primary treatment for patients with **Diffuse Large B-Cell Lymphoma**. This is a randomized, open-label, phase III trial conducted by the Nordic Lymphoma Group. The trial involves a comparison of two treatment regimens, with the primary endpoint being progression-free survival. Secondary endpoints include response duration, complete remission rate, overall response rate, health-related quality of life, overall survival, lymphoma-specific survival, and safety.

The trial is expected to run from August 19, 2020, to December 31, 2025. Participants will be involved in the study for a maximum treatment period of 126 days, depending on the specific regimen they are assigned to. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor treatment response and safety, and an end-of-study visit to assess final outcomes. Participants must meet specific inclusion criteria, such as being 80 years or older, or frail individuals aged 75 years or older, with histologically confirmed lymphoma of certain subtypes and stage II-IV disease. Exclusion criteria are not specified in the provided data.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The trial involves the administration of several drugs, including **prednisone**, **polatuzumab vedotin**, **rituximab**, **cyclophosphamide**, **vincristine sulfate**, and **doxorubicin hydrochloride**, with specific dosing regimens and routes of administration. The trial is not categorized as low intervention and is conducted under the regulatory framework for phase III trials.

The clinical trial involves the administration of several **experimental medications** and standard-of-care therapies. **Prednisone** is administered in tablet form, with a maximum daily dose of 40 mg/m² and a total dose not exceeding 1200 mg/m² over a treatment period of 126 days. The route of administration is periosseous use. Compliance with the dosing schedule is monitored throughout the trial.

**Polatuzumab vedotin**, marketed as Polivy, is provided as a powder for concentrate for solution for infusion. The maximum daily dose is 1.8 mg/kg, with a total dose limit of 10.8 mg/kg over 126 days. It is administered via infusion. This medication is designated as an orphan drug and is used in combination with other treatments in the trial.

**Rituximab** is utilized in two forms: as a solution for injection and as a solution for infusion. The subcutaneous injection form has a maximum daily dose of 1400 mg, with a total dose of 7000 mg over 105 days. The infusion form is dosed at 375 mg/m² daily, with a total dose of 2250 mg/m² over 126 days. Both forms are integral to the trial's treatment regimen.

**Cyclophosphamide** is administered as a solution for injection or infusion, with a maximum daily dose of 400 mg/m² and a total dose of 2400 mg/m² over 105 days. The route of administration is intravenous infusion, and it is categorized under chemotherapy treatments in the study.

**Vincristine sulfate** is provided as a solution for infusion, with a maximum daily dose of 1 mg and a total dose of 6 mg over 126 days. It is administered intravenously and is part of the chemotherapy regimen in the trial.

**Doxorubicin hydrochloride** is administered as a solution for infusion, with a maximum daily dose of 25 mg/m² and a total dose of 150 mg/m² over 105 days. The route of administration is intravenous infusion, and it is also classified as a chemotherapy agent in the study.

Participant compliance with the dosing schedules is closely monitored to ensure adherence to the treatment protocols. The trial aims to evaluate the efficacy of the combination of these treatments in patients with diffuse large B-cell lymphoma, particularly focusing on the comparison between R-mini-CHOP and pola-R-mini-CHP regimens.

The efficacy of the clinical trial will be assessed using a combination of primary and secondary endpoints. The primary endpoint is **progression-free survival**, which will be measured to evaluate the efficacy of the treatment regimen pola-R-mini-CHP compared to R-mini-CHOP in patients with diffuse large B-cell lymphoma. Secondary endpoints include response duration, complete remission rate, overall response rate, health-related quality of life, overall survival, lymphoma-specific survival, and safety. These endpoints will provide a comprehensive evaluation of the treatment's impact on the disease and patient well-being.

Data collection and analysis will be conducted at specified intervals throughout the trial. The trial is designed as an open-label, randomized phase III study, and the efficacy parameters will be measured using validated clinical assessment tools and patient-reported outcomes. The trial is expected to conclude by December 31, 2025, with recruitment having started on August 19, 2020. The results will be analyzed to determine the comparative efficacy of the treatment regimens in the specified patient population.