Phase II Evaluation of Fludarabine and Treosulfan Conditioning Regimen for Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia Patients Aged 40-65

The primary objective of this prospective Phase II study is to evaluate the **safety** and **efficacy** of the Fludarabine plus Treosulfan (14g) (FT14) conditioning regimen for allogeneic Stem Cell Transplantation (allo-SCT) in patients with **Acute Myeloid Leukemia (AML)** aged between 40 and 65 years who are in complete morphological remission (CR/CRi/MLFS). This evaluation is clinically relevant as it aims to determine the potential of the FT14 regimen to improve outcomes in AML patients undergoing allo-SCT, a critical treatment option for this patient population.

The clinical trial involves participants diagnosed with **Acute Myeloid Leukemia (AML)**, specifically those in complete morphological remission. The study population includes both male and female subjects aged between 40 and 65 years. Participants are required to have adequate hepatic and renal function, as well as an ECOG Performance Status of less than 2. The trial does not include a vulnerable population. The selection criteria ensure that participants are eligible for allogeneic stem cell transplantation (allo-SCT) from an HLA-identical matched related or unrelated donor. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **Phase II** study designed to evaluate the safety and efficacy of a conditioning regimen comprising **fludarabine** and **treosulfan** for allogeneic stem cell transplantation in patients with **Acute Myeloid Leukemia (AML)**. The trial employs a **randomized, double-blind, controlled** design to ensure the reliability and validity of the results. The estimated duration of the trial is from September 30, 2022, to September 30, 2025, with the primary endpoint being the 1-year leukemia-free survival after transplantation.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and organ function. The inclusion criteria specify that participants must be between 40 and 65 years old, have a diagnosis of AML in complete remission, and be eligible for transplantation from an HLA-identical matched donor. Following the screening, participants will receive the study treatment and attend regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, assessing the final outcomes and any adverse events.

The expected length of participant involvement is approximately three years, aligning with the overall trial duration. Conditions that may lead to early termination from the study include significant adverse reactions, withdrawal of consent, or non-compliance with study protocols. The trial aims to provide valuable insights into the potential benefits and risks of the conditioning regimen, contributing to the optimization of treatment strategies for AML patients undergoing stem cell transplantation.

The clinical trial involves the administration of **Treosulfan**, marketed as Treosulfan Tillomed 5g polvere per soluzione per infusione. This experimental medication is provided in the form of a **solution for infusion**. The active substance, treosulfan, is a chemical compound with an ATC code of L01AB02. The maximum daily dose is 14 mg/m², with a total maximum dose of 30 gm/m² over a treatment period of up to 3 days. The route of administration is via infusion.

**Fludarabine Phosphate** is another experimental medication used in this trial, marketed as FLUDARABINE TEVA 25 mg/ml, solution à diluer pour injectable ou perfusion. It is provided as an **injection** and is also administered via infusion. The maximum daily dose is 30 mg/m², with a total maximum dose of 150 mg/m² over a treatment period of up to 5 days. The ATC code for fludarabine is L01BB05.

**Ciclosporin** is used as a non-experimental treatment in this study. It is an immunosuppressant administered via **parenteral use**. The maximum daily dose is 3.5 mg/kg, with a total maximum dose of 52.5 mg/kg over a treatment period of up to 2 weeks. The ATC code for ciclosporin is L04AD01.

**Mycophenolic Acid**, also known as mycophenolate, is another non-experimental treatment used in the study. It is administered as an **infusion**. The maximum daily dose is 2.5 mg/kg, with a total maximum dose of 10 mg/kg over a treatment period of up to 4 days. The ATC code is L04AA04.

**Methotrexate Sodium** is included as a non-experimental treatment, provided in the form of an **infusion**. The maximum daily dose is 30 mg, with a total maximum dose of 150 mg over a treatment period of up to 5 days. The ATC code for methotrexate is L01BA01.

**Anti-T Lymphocyte Immunoglobulin for Human Use, Rabbit**, marketed as Grafalon 20 mg/ml concentrato per soluzione per infusione, is used as a non-experimental treatment. It is a structurally diverse substance derived from blood, administered via **infusion**. The maximum daily dose is 20 mg/kg, with a total maximum dose of 60 mg/kg over a treatment period of up to 3 days. The ATC code is L04AA04.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint of 1-year leukemia-free survival (LFS) following allogeneic stem cell transplantation (allo-SCT) in patients with **Acute Myeloid Leukemia (AML)**. The trial aims to determine the effectiveness of the Fludarabine plus Treosulfan (FT14) conditioning regimen in achieving complete morphological remission in AML patients aged 40 to 65 years. The assessment will focus on the survival rate without leukemia recurrence one year post-transplantation.