Efficacy and Safety Evaluation of Golcadomide with Rituximab in Newly Diagnosed Advanced Stage Follicular Lymphoma: A Phase 2 Randomized Open-Label Study

The primary objective of this study is to evaluate the **Complete Metabolic Response (CMR)** in patients with newly diagnosed advanced stage follicular lymphoma. CMR is clinically significant as it indicates the absence of detectable cancer following treatment, which is a critical marker for assessing the effectiveness of the therapeutic regimen.

Secondary objectives include:

• Evaluating the safety of the combination of Golcadomide at two dose levels with **rituximab**.
• Determining the optimal dose of the combination for use in larger studies.
• Assessing the overall response to treatment and the duration of these responses.
• Evaluating **Progression-Free Survival (PFS)**, defined as the time from study initiation until disease progression or death.
• Assessing the efficacy of Golcadomide in combination with rituximab regarding **Overall Survival (OS)**, which measures the time from study start until death.
• Evaluating the efficacy of rituximab plus chemotherapy in participants with newly diagnosed advanced stage follicular lymphoma concerning CMR and the duration of responses.

The clinical trial involves a total of **113 participants** diagnosed with **Newly Diagnosed Advanced Stage Follicular Lymphoma**. The study population includes both male and female subjects, all of whom are over the age of 18. Participants were selected based on specific inclusion criteria, which required them to meet certain disease characteristics, laboratory values, and reproductive capacity status. The trial does not include a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits were not specified in the available data. The selection process ensured a diverse representation of eligible individuals to evaluate the Complete Metabolic Response (CMR) effectively.

The clinical trial is a **Phase II** randomized, open-label study designed to evaluate the efficacy and safety of **Golcadomide** in combination with **Rituximab** in patients with newly diagnosed advanced stage **follicular lymphoma**. The trial aims to assess the complete metabolic response (CMR) as the primary endpoint, with secondary endpoints including the evaluation of adverse events, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The trial is expected to commence recruitment on October 14, 2024, and conclude by November 15, 2028.

Participants will be randomly assigned to receive either the investigational treatment or a comparator. The investigational treatment involves the administration of Golcadomide orally in capsule form, while Rituximab is administered subcutaneously. The trial will include a screening visit to confirm eligibility based on inclusion criteria such as age over 18 and specific disease characteristics. Participants will undergo regular follow-up visits to monitor treatment response and safety, with assessments conducted at intervals such as 6 and 12 months post-treatment initiation. The end-of-study visit will evaluate the overall treatment outcomes and any long-term effects.

The expected duration of participant involvement varies, with the maximum treatment period for Golcadomide being 336 days. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or disease progression. Participants will be closely monitored throughout the trial to ensure safety and efficacy, with data collected on treatment-emergent adverse events and laboratory test results. The trial's design and procedures are structured to provide comprehensive data on the investigational treatment's impact on follicular lymphoma, contributing to the understanding of its potential benefits and risks.

**Golcadomide** is the primary experimental medication in this clinical trial. It is administered in the form of a **capsule** and is taken **orally**. The maximum daily dose is **0.4 mg**, with a total maximum dose of **67.2 mg** over a treatment period of up to **336 days**. The active substance, **golcadomide**, is chemically derived and is provided by Celgene Corporation. Participant compliance with the dosing schedule is monitored throughout the trial.

**Rituximab** is used as a comparator treatment in this study. It is available in two pharmaceutical forms: a **solution for injection** and a **solution for infusion**. The subcutaneous route involves a maximum daily dose of **1400 mg** and a total maximum dose of **28000 mg** over **24 weeks**. The intravenous form is dosed at **375 mg/m²** with a total maximum dose of **7875 mg/m²** over the same period. Rituximab is a protein-based medication, and its administration is closely monitored to ensure adherence to the protocol.

**Prednisone** is another comparator treatment, provided in **tablet** form for **oral use**. The maximum daily dose is **100 mg**, with a total maximum dose of **3000 mg** over a treatment period of **126 days**. Prednisone is a chemically synthesized corticosteroid, and its administration is monitored to ensure participant compliance.

**Bendamustine Hydrochloride** is administered as a **powder for concentrate for solution for infusion** via the **intravenous** route. The maximum daily dose is **90 mg/m²**, with a total maximum dose of **1080 mg/m²** over **168 days**. This chemically derived medication is used as a comparator in the trial.

**Vincristine Sulfate** is provided as a **solution for injection** and is administered **intravenously**. The maximum daily dose is **2 mg**, with a total maximum dose of **12 mg** over **126 days**. This chemical compound is used as a comparator treatment in the study.

**Cyclophosphamide** is administered as a **powder for solution for injection/infusion** via the **intravenous** route. The maximum daily dose is **750 mg/m²**, with a total maximum dose of **4500 mg/m²** over **126 days**. This chemically synthesized medication is used as a comparator in the trial.

**Pegfilgrastim** is used as an auxiliary treatment in the study. It is provided as a **solution for injection** and administered **subcutaneously**. The dosing is based on **mg/ml**, with a maximum daily and total dose of **9999 mg/ml**. The treatment period is not specified, indicating continuous monitoring and administration as needed.

**Doxorubicin** is administered as a **solution for injection** via the **intravenous** route. The maximum daily dose is **50 mg/m²**, with a total maximum dose of **300 mg/m²** over **126 days**. This chemically derived medication is used as a comparator in the trial.

**Betamethasone Sodium Phosphate** is provided as a **solution for injection** and administered **intravenously**. The maximum daily dose is **100 mg**, with a total maximum dose of **600 mg** over **18 days**. This chemical compound is used as a comparator treatment in the study.

The efficacy of the clinical trial will be assessed primarily through the evaluation of the **Complete Metabolic Response (CMR)**. This endpoint is defined as the absence of detectable cancer in the body at the end of the treatment period. The primary endpoint will be measured at various timepoints, such as 6 months and 12 months after the initiation of treatment, to determine if the patient's condition has completely responded to the treatment.

Secondary endpoints include the assessment of adverse events (AEs), including Treatment-Emergent Adverse Events (TEAEs), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ORR will be evaluated as the percentage of participants whose cancer shrinks or disappears. PFS will be measured as the time from the start of treatment until disease progression or death, while OS will be the time from treatment initiation until death. These parameters will be collected and analyzed throughout the treatment period to provide a comprehensive evaluation of the treatment's efficacy and safety.