Evaluation of Brentuximab Vedotin, Doxorubicin Hydrochloride, Dacarbazine, and Nivolumab in Untreated Classical Hodgkin Lymphoma Patients

The primary objective of this clinical trial is to evaluate the **complete response (CR) rate** at the end of treatment (EOT) with the combination of brentuximab vedotin and other agents in subjects with previously untreated **Classical Hodgkin Lymphoma (cHL)**. This objective is clinically relevant as achieving a complete response is indicative of the absence of detectable disease, which is a critical endpoint in the treatment of cHL, potentially leading to improved long-term outcomes for patients.

The clinical trial involves a total of **233 participants** diagnosed with **Classical Hodgkin Lymphoma** (cHL). The study population includes both male and female subjects, with an age range starting from 12 years in the United States and 18 years in other regions. Participants are required to have a histologically confirmed diagnosis of cHL, as per the current World Health Organization Classification, and must present with bidimensional measurable disease documented by PET/CT or CT imaging. The trial specifically targets treatment-naïve individuals with Ann Arbor Stage I or II cHL without bulky mediastinal disease. All participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, indicating they are ambulatory and capable of all self-care but unable to carry out any work activities. The selection process did not focus on any vulnerable populations, and no specific lifestyle considerations such as diet or physical activity were highlighted in the trial criteria.

The clinical trial is designed to evaluate the efficacy and tolerability of **brentuximab vedotin** alone or in combination with other anticancer therapies in subjects with **Classical Hodgkin Lymphoma** (cHL). This is a phase 2, randomized, double-blind, controlled trial. The trial is expected to run from July 2021 to November 2027, with the primary objective being to assess the complete response rate at the end of treatment (EOT) in subjects with previously untreated cHL. Secondary endpoints include the incidence, severity, seriousness, and relatedness of adverse events (AEs), as well as the incidence and severity of laboratory abnormalities, overall response rate (ORR), duration of response (DOR), duration of complete response (DOCR), event-free survival (EFS), and progression-free survival (PFS).

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed cHL, bidimensional measurable disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. The trial will include multiple follow-up visits to monitor treatment response and safety, with the end-of-study visit marking the conclusion of participant involvement. The expected length of participant involvement is up to 10 treatment cycles, with each cycle lasting approximately 3 weeks. Conditions that may lead to early termination from the study include the occurrence of unacceptable toxicity, disease progression, or withdrawal of consent by the participant.

The clinical trial involves the administration of several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Dacarbazine Lipomed** is provided as a 500 mg powder for solution for infusion. It is an alkylating agent with cytostatic properties, administered intravenously. The maximum daily dose is 850 mg/m², with a total maximum dose of 10,200 mg/m² over a treatment period of up to 4 cycles. Participant compliance is monitored through regular assessments of infusion administration and dosage adherence.

**Doxorubicin Hydrochloride**, marketed as DOXORUBICINE ACCORD, is available as a 2 mg/ml solution for infusion. This antineoplastic cytostatic antibiotic belongs to the anthracycline family and is administered via intravenous infusion. The maximum daily dose is 90 mg/m², with a total maximum dose of 360 mg/m² over a treatment period of up to 4 cycles. Compliance is ensured by monitoring infusion schedules and dosage accuracy.

**Brentuximab Vedotin**, under the brand name ADCETRIS, is supplied as a 50 mg powder for concentrate for solution for infusion. It is an antibody-drug conjugate administered through intravenous administration. The dosing regimen includes a maximum daily dose of 1.2 mg/kg, with a total maximum dose of 120 mg over a treatment period of up to 10 cycles. Participant adherence is tracked through infusion records and dose verification.

**Nivolumab**, marketed as OPDIVO, is provided as a 10 mg/mL concentrate for solution for infusion. It is administered via intravenous infusion, with a maximum daily dose of 10 mg/mL and a total maximum dose of 240 mg over a treatment period of up to 4 cycles. Compliance is monitored by ensuring adherence to the infusion protocol and dosage accuracy.

All medications are administered in a controlled clinical setting, with participant compliance monitored through infusion records and regular assessments to ensure adherence to the dosing schedules. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments.

The efficacy of the clinical trial will be assessed primarily by evaluating the complete response (CR) rate at the end of treatment (EOT) in subjects with previously untreated classical Hodgkin lymphoma (cHL). This primary endpoint will provide a measure of the proportion of patients achieving a complete response following the treatment regimen. Secondary endpoints will include the incidence, severity, seriousness, and relatedness of adverse events (AEs), as well as the incidence and severity of laboratory abnormalities. Additional secondary efficacy parameters will encompass the overall response rate (ORR), duration of response (DOR), duration of complete response (DOCR), event-free survival (EFS), and progression-free survival (PFS).

The trial will utilize imaging techniques such as PET/CT or CT to document bidimensional measurable disease, which will be critical in assessing the response to treatment. The schedule for measuring these efficacy parameters will align with the trial's design, ensuring that data collection occurs at appropriate intervals to capture meaningful changes in the disease state. The analysis of these endpoints will be conducted using validated methodologies to ensure the reliability and accuracy of the results. The trial is designed to provide comprehensive insights into the efficacy of **brentuximab vedotin** in combination with other anticancer therapies, contributing to the understanding of its therapeutic potential in cHL.