Prospective Study on Nilotinib Versus Imatinib with Nilotinib Switch in BCR-ABL+ Chronic Myeloid Leukemia in Chronic Phase

The primary objective of this study is to evaluate the **efficacy** of Nilotinib (NIL) as a frontline therapy compared to Imatinib (IM) in newly diagnosed patients with Chronic Myeloid Leukemia (CML) in the Chronic Phase (CP). In cases where an optimal response is not achieved with IM, a switch to NIL will be implemented, as defined by the European LeukemiaNet (ELN) criteria. This objective is clinically relevant as it aims to determine the most effective initial treatment strategy for achieving sustained treatment-free remission in CML patients, potentially improving long-term outcomes and quality of life.

Secondary objectives include: - Monitoring the molecular response. - Assessing progression-free survival (PFS) and overall survival in the two study arms. - Evaluating rates of major molecular response (MR3.0) during the study. - Investigating the dynamics of molecular response. - Exploring the relationship between baseline characteristics and the primary objectives, as well as between early molecular response and the primary objectives. - Assessing the safety profile of both treatment arms. - Determining the rate and time-distribution of discontinuation causes of the first-line tyrosine kinase inhibitor (TKI). - Investigating quality of life (QoL) differences between treatment arms over time.

The clinical trial focuses on patients diagnosed with **Chronic Myeloid Leukemia (CML) in Chronic Phase (CP)**. The study population includes both male and female participants, aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, indicating they are ambulatory and capable of self-care. Participants must have adequate end organ function and evidence of typical BCR-ABL transcripts suitable for standardized RQ-PCR. The trial does not specify the total number of participants, as this information was not provided by the sponsor. The selection criteria ensure that participants have a confirmed diagnosis of BCR/ABL+ CML in the chronic phase, with specific hematological parameters. The study population may include individuals from vulnerable groups, although specific lifestyle considerations such as diet or physical activity are not detailed in the available data.

The clinical trial is designed to evaluate the efficacy of **nilotinib** as a frontline therapy compared to **imatinib**, with a switch to nilotinib in the absence of an optimal response, in patients with **Chronic Myeloid Leukemia (CML)** in the chronic phase. This is a prospective, randomized, controlled, and open-label study. The trial aims to assess the rates of molecular response (MR4.5) at 24 months and the rate of patients who remain in sustained treatment-free remission without molecular relapse 12 months after entering the treatment-free remission phase. Secondary endpoints include determining the depth of molecular response by four years, estimating progression-free survival and overall survival at 60 months, and assessing the safety profile of both treatment arms.

The trial is expected to last approximately 10 years, with an estimated recruitment start date in November 2016 and an estimated end date in January 2026. Participants will be involved in the study for a maximum treatment period of 48 months. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor response and safety, and an end-of-study visit to assess final outcomes. Participants must meet specific inclusion criteria, such as being 18 years or older, having a confirmed diagnosis of BCR-ABL+ CML in the chronic phase, and having adequate end organ function. Conditions that may lead to early termination from the study include significant adverse events, lack of compliance, or withdrawal of consent.

The clinical trial involves the administration of two experimental medications, **Glivec** and **Tasigna**, both of which are utilized in the treatment of BCR-ABL+ chronic myeloid leukemia. **Glivec** is presented in the form of 100 mg hard capsules, with the active substance being **imatinib**. The pharmaceutical form is a hard capsule, and the medication is administered orally. The maximum daily dose for **Glivec** is 400 mg, with a total maximum dose of 584 g over the treatment period. The treatment period is set for a maximum of 48 months. **Glivec** is a chemical substance, and its administration is monitored to ensure compliance with the dosing schedule.

**Tasigna** is another experimental medication used in this study, presented as 150 mg hard capsules containing the active substance **nilotinib**. Similar to **Glivec**, **Tasigna** is administered orally in the form of hard capsules. The maximum daily dose for **Tasigna** is 600 mg, with a total maximum dose of 876 g over the treatment period, which is also set for a maximum of 48 months. **Tasigna** is a chemical substance, and participant compliance with the dosing schedule is closely monitored throughout the study.

Both medications are produced by Novartis Europharm Limited and are not formulated for pediatric use. The trial does not involve any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The study aims to evaluate the efficacy of **nilotinib** as a frontline therapy compared to **imatinib**, with a switch to **nilotinib** in the absence of an optimal response, as defined by the European LeukemiaNet (ELN) criteria.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include evaluating the rates of molecular response (MR4.5) at 24 months and assessing the rate of patients who remain in sustained treatment-free remission (TFR) at MR3.0 without molecular relapse 12 months after entering the TFR phase. Molecular relapse is defined as the loss of major molecular response (MMR) or confirmed loss of MR3.0.

Secondary endpoints will focus on determining the depth of molecular response by 4 years, estimating progression-free survival (PFS) and overall survival in the two arms of the study at 60 months, and determining the rates of major molecular response (MR3.0) at 1, 2, 3, and 4 years. Additional assessments will include the dynamics of molecular response, the relationship between baseline characteristics and the achievement of MR4.5, and the sustained treatment-free remission rate at MR3.0. The relationship between early molecular response and the achievement of MR4.5 and sustained TFR rate will also be evaluated. Safety profiles of both Nilotinib (NIL) and Imatinib (IM) arms will be assessed, along with the rate and time-distribution of discontinuation of the first-line tyrosine kinase inhibitor (TKI) due to side effects, toxicity, and adverse events (AEs). Quality of life (QoL) differences between treatment arms over time will also be investigated.