Phase 2 Open-Label Study of Brentuximab Vedotin and CHP in Frontline Treatment of Peripheral T-Cell Lymphoma with <10% CD30 Expression

The primary objective of this study is to evaluate the **overall response rate (ORR)** per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma. This is clinically relevant as it provides a standardized assessment of treatment efficacy in patients with **Peripheral T-cell Lymphoma** (PTCL), particularly those with less than 10% CD30 expression, which is crucial for determining the potential benefit of the treatment regimen involving brentuximab vedotin and CHP (A+CHP).

Secondary objectives include:

• Evaluating the complete response (CR) rate following completion of study treatment.
• Assessing progression-free survival (PFS).
• Evaluating overall survival (OS).
• Determining the duration of response (DOR).
• Evaluating ORR per BICR using modified Lugano criteria.
• Assessing the safety and tolerability of the treatment regimen.

These secondary objectives are important for providing a comprehensive understanding of the treatment's impact on disease progression, patient survival, and safety profile, which are critical factors in the management of PTCL.

The clinical trial involves a total of **44 participants** diagnosed with **Peripheral T-cell Lymphoma**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on specific inclusion criteria, including a diagnosis of newly diagnosed Peripheral T-cell Lymphoma, excluding systemic anaplastic large cell lymphoma, as per the Revised European-American Lymphoma World Health Organization 2016 classification. The trial population is characterized by a diverse range of T-cell lymphoma subtypes, with a requirement for CD30 expression of less than 10% by local assessment. Participants are required to have an Eastern Cooperative Oncology Group performance status of 2 or less, and specific baseline laboratory data must be met. The study also includes individuals who are HIV-positive, provided they meet certain health criteria. Both males and females of childbearing potential must adhere to effective contraceptive measures during and after the study. The trial population is considered vulnerable, and all participants or their legally authorized representatives must provide written informed consent. The sponsor has not provided additional information regarding lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **phase 2**, open-label study to evaluate the efficacy of **brentuximab vedotin** in combination with CHP (cyclophosphamide, doxorubicin, and prednisone) for the frontline treatment of subjects with **Peripheral T-cell Lymphoma** (PTCL) exhibiting less than 10% CD30 expression. The primary objective is to assess the overall response rate (ORR) per blinded independent central review (BICR) using the Revised Response Criteria for Malignant Lymphoma. Secondary endpoints include complete response rate, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and the incidence and severity of adverse events.

The trial is expected to span approximately 4.5 years, with an estimated recruitment start date of July 28, 2021, and an anticipated end date of January 19, 2026. Participants will be involved in the study for a maximum treatment period of 6 months. 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. The inclusion criteria require participants to be 18 years or older, with newly diagnosed PTCL, excluding systemic anaplastic large cell lymphoma (sALCL), and to meet specific laboratory and health status requirements. Exclusion criteria are not explicitly detailed in the provided data.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, withdraw consent, or if the investigator deems it in the participant's best interest. The study drugs include **brentuximab vedotin** administered via intravenous infusion, and CHP components, which include **cyclophosphamide** and **doxorubicin hydrochloride** administered intravenously, and **prednisone** administered orally. The trial is not categorized as low intervention and is conducted under standard clinical trial regulations to ensure participant safety and data integrity.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. The primary experimental medication is **Brentuximab Vedotin**, an **antibody-drug conjugate**. It is provided as a powder for concentrate for solution for infusion and is administered via **intravenous administration**. The dosing regimen involves a maximum daily dose of 1.8 mg/kg, with a total treatment period of up to 6 months. This medication is designated as an orphan drug, indicating its use in rare conditions.

**Prednisone** is used as a comparator treatment in various dosages: 5 mg, 10 mg, 20 mg, and 50 mg, all formulated as tablets for **oral use**. The maximum daily dose for each formulation is 100 mg/m², with a treatment period extending up to 6 months. Prednisone is classified as a **corticosteroid** and is chemically synthesized. The manufacturer for these formulations is GALENPHARMA GMBH.

**Cyclophosphamide** is another comparator treatment, provided as a 500 mg powder for solution for injection or infusion. It is administered as a **solution for injection**, with a maximum daily dose of 750 mg/m². The treatment duration is also up to 6 months. Cyclophosphamide is a **chemotherapeutic agent** and is chemically derived, manufactured by SANDOZ LTD.

**Doxorubicin Hydrochloride** is included as a comparator, available as a 2 mg/ml solution for infusion. It is administered via **intravenous administration**, with a maximum daily dose of 50 mg/m² over a treatment period of 6 months. This agent is classified under **chemotherapeutic agents** and is chemically synthesized, produced by ACCORD HEALTHCARE FRANCE SAS.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to evaluate the overall response rate using the Revised Response Criteria for Malignant Lymphoma, as assessed by a blinded independent central review.

Efficacy in this clinical trial will be assessed primarily through the **Overall Response Rate (ORR)** as determined by a Blinded Independent Central Review (BICR) using the Revised Response Criteria for Malignant Lymphoma. This primary endpoint will be evaluated following the completion of the study treatment. Secondary endpoints include the complete response rate, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and ORR using modified Lugano criteria, all assessed per BICR. Additionally, the type, incidence, severity, seriousness, and relatedness of adverse events, as well as laboratory abnormalities, will be monitored.