International cooperative prospective study for children and adolescents with standard risk ALK-positive anaplastic large cell lymphoma (ALCL) estimating the efficacy of Vinblastine

The primary objective of this study is to demonstrate the potential to cure at least 75% of patients with **standard risk ALK-positive anaplastic large cell lymphoma (ALCL)** using Vinblastine monotherapy over a 24-month period. This objective is clinically significant as it aims to establish a less intensive treatment regimen that could potentially reduce the long-term side effects associated with more aggressive therapies, while maintaining high efficacy in treating this specific lymphoma subtype.

Secondary objectives include:

• Describing overall survival and treatment-related mortality associated with 24 months of Vinblastine monotherapy, where overall survival is defined as the time from diagnosis to death from any cause or last follow-up.
• Identifying clinical, pathological, and biological factors predictive of progressive disease during or after Vinblastine therapy, with progressive disease defined as the time from diagnosis to disease progression or a competing event such as death from any cause or secondary malignancy, or last follow-up.
• Estimating the rate of patients requiring multi-agent chemotherapy.
• Describing the toxicity of Vinblastine administered for 24 months, evaluated using the CTCAE v4.03 criteria.
• Describing the response to treatment after 3 weeks (between days 17-22), 3 months, and 6 months, assessed by appropriate imaging methods.

The clinical trial involves participants diagnosed with **standard risk ALK-positive anaplastic large cell lymphoma (ALCL)**. The study population includes both male and female subjects under the age of 18, indicating a pediatric focus. Participants are stratified into the standard risk group based on specific criteria, including newly diagnosed ALK-positive ALCL, stage I not completely resected, or stage II or III, and minimal disseminated disease (MDD) negative. The trial population is selected with consideration for vulnerable populations, as it includes minors. The sponsor has not provided the total number of participants. Key lifestyle considerations include the requirement for sexually active patients to use a highly effective contraceptive method. The trial necessitates informed consent from parents or legal guardians, along with the assent of the competent child, prior to study entry. Participants are expected to be followed up for at least three years after enrollment.

The clinical trial is designed to evaluate the efficacy of **vinblastine sulfate** in treating children and adolescents with standard risk ALK-positive anaplastic large cell lymphoma (ALCL). This study is a prospective, randomized, double-blind, controlled trial with an estimated duration from January 2020 to January 2028. The primary objective is to demonstrate that at least 75% of patients in the standard risk group can be cured with vinblastine monotherapy over a 24-month period. The trial will assess the probability of event-free survival (pEFS) at three years, with event-free survival defined as the time from diagnosis to the first event, such as progressive disease, nonresponse, secondary malignancy, or death from any cause.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age under 18 years, newly diagnosed ALK-positive ALCL, and informed consent from parents or legal guardians. The trial requires follow-up for at least three years post-enrollment. The treatment regimen includes the administration of vinblastine sulfate via intravenous use, with a maximum daily dose of 10 mg and a total dose not exceeding 504 mg over the treatment period. Participants will also receive one intrathecal triple therapy with Methotrexate, Cytarabine, and Prednisolone (or Hydrocortisone) before starting the protocol treatment.

Study visits will include regular follow-up assessments to monitor the patient's response to treatment and any adverse events. The end-of-study visit will occur at the conclusion of the 24-month treatment period or upon early termination. Conditions that may lead to early termination from the study include the occurrence of progressive disease, nonresponse, or any serious adverse events that compromise patient safety. The expected length of participant involvement is approximately three years, including the treatment and follow-up periods. The trial is not classified as a low-intervention study and is categorized under trial phase 5, with decisions made according to the primary trial objectives.

The clinical trial involves the use of **Vinblastine Sulfate**, an experimental medication, to evaluate its efficacy in treating children and adolescents with standard risk ALK-positive anaplastic large cell lymphoma (ALCL). **Vinblastine Sulfate** is a vinka-alkaloid and antimicrotubule drug, administered in the form of a solution for injection or infusion. The pharmaceutical form is specifically designed for **intravenous use**. The dosing regimen for this trial involves a maximum daily dose of 10 mg, with a total maximum dose of 504 mg/m² over the course of the treatment. The treatment period is set for a maximum of 24 months, during which the participants will receive the medication as per the specified dosing schedule.

In this study, **Vinblastine Sulfate** is the sole experimental treatment, and no additional non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial aims to demonstrate the potential of **Vinblastine Sulfate** monotherapy to cure at least 75% of patients in the standard risk group. Participant compliance with the dosing schedule will be closely monitored to ensure adherence to the treatment protocol. The trial does not involve any pediatric-specific formulations, and the medication is not classified as an orphan drug. The study is conducted under strict clinical guidelines to ensure the safety and efficacy of the treatment for the participants.

The efficacy of Vinblastine in treating children and adolescents with standard risk ALK-positive anaplastic large cell lymphoma (ALCL) will be assessed through the primary endpoint of the probability of event-free survival (pEFS) at 3 years. Event-free survival is defined as the time from diagnosis to the first occurrence of progressive disease, nonresponse, secondary malignancy, or death from any cause, or until the last follow-up. This endpoint will provide a measure of the treatment's ability to prevent disease progression and other adverse outcomes over a specified period.