Magrolimab plus intensive chemotherapy in newly diagnosed “ELN intermediate or poor-risk” AML patients intended to undergo allogeneic stem cell transplantation, a Phase 2, Single-arm, Open-Label Study (MAGROLIC)

The primary objective of this Phase 2, single-arm, open-label study is to evaluate the **best complete remission (CR)**, complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh) during induction chemotherapy in patients with newly diagnosed "ELN intermediate or poor-risk" acute myeloid leukemia (AML) who are intended to undergo allogeneic stem cell transplantation. This objective is clinically relevant as achieving CR, CRi, or CRh is a critical indicator of treatment efficacy and a predictor of long-term outcomes in AML patients.

Secondary objectives include:

• Overall Survival
• Event-Free Survival
• Relapse-Free Survival
• Rate of allogeneic hematopoietic stem cell transplantation
• Quality of life
• Rate and severity of adverse events for patients treated with **magrolimab** and induction chemotherapy

These secondary objectives aim to provide a comprehensive assessment of the treatment's impact on survival, relapse rates, transplantation success, patient quality of life, and safety profile, which are essential for understanding the broader clinical benefits and risks associated with the treatment regimen.

The clinical trial involves participants diagnosed with **high-risk myelodysplastic neoplasia** or **acute myeloid leukemia**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. The trial does not specifically target a vulnerable population. Participants were selected based on their diagnosis of AML or MDS-IB-2 according to WHO 2022 criteria and categorized as "intermediate or adverse risk" per ELN 2022 guidelines. The intention to undergo intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation is a key consideration for inclusion. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is a Phase 2, single-arm, open-label study designed to evaluate the efficacy of **Magrolimab** in combination with intensive chemotherapy in patients newly diagnosed with "ELN intermediate or poor-risk" **acute myeloid leukemia** (AML) or high-risk myelodysplastic neoplasia. The primary objective is to assess the best complete remission (CR), complete remission with incomplete hematologic recovery (CRi), or complete remission with partial hematologic recovery (CRh) during induction chemotherapy. The trial will include a maximum of two induction cycles, with the primary endpoint being the achievement of CR/CRi/CRh at the end of induction therapy. Secondary endpoints include overall survival, event-free survival, relapse-free survival, rate of allogeneic hematopoietic stem cell transplantation, and quality of life assessments using validated questionnaires.

The trial is expected to commence recruitment on October 2, 2023, and is estimated to conclude by September 30, 2028. Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as AML or MDS-IB-2 according to WHO 2022 criteria and intention to undergo intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation. Follow-up visits will be conducted to monitor treatment response, adverse events, and overall health status. The end-of-study visit will occur after the completion of the treatment regimen or upon early termination from the study.

Participant involvement is anticipated to last up to four months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include non-achievement of complete remission after two induction chemotherapies, hematological relapse, or any adverse events that compromise participant safety. The study will employ a rigorous methodology to ensure the collection of comprehensive data on the safety and efficacy of the treatment regimen, with all adverse events and serious adverse events being collected, graded, and coded according to standardized criteria.

The clinical trial involves the administration of **Magrolimab**, an experimental medication formulated as a **solution for infusion**. The active substance in Magrolimab is **HU5F9-G4**, a structurally diverse substance classified as an immunoglobulin. This medication is secreted by a genetically engineered CHOK1SV cell line. The dosage is set at a maximum of 30 mg/kg per day, administered intravenously. The treatment period is limited to a maximum of four weeks. Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to Magrolimab, the study includes the administration of **Cytarabin Accord 100 mg/ml**, a **solution for injection/infusion**. The active substance is **Cytarabine**, a chemical compound. The maximum daily dose is 1 mg/m², with the same maximum treatment period of four weeks. This medication is administered via infusion, and participant adherence to the dosing regimen will be closely observed.

Another treatment used in the trial is **Vyxeos Liposomal 44 mg/100 mg**, a powder for concentrate for **solution for infusion**. This formulation contains two active substances: **Cytarabine** and **Daunorubicin**, both of which are chemical compounds. The maximum daily dose is 100 mg/m², administered through infusion over a four-week period. Compliance with the dosing schedule will be monitored to ensure accurate administration.

The trial also includes **Daunoblastin® 20 mg**, a powder for the preparation of a **solution for injection/infusion**. The active substance is **Daunorubicin Hydrochloride**, a chemical compound. The maximum daily dose is 60 mg/m², with a treatment period of up to four weeks. This medication is administered via infusion, and participant compliance will be tracked to maintain dosing accuracy.

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the achievement of **CR/CRi/CRh** (complete remission, complete remission with incomplete hematologic recovery, or complete remission with partial hematologic recovery) at the end of induction therapy, which may consist of up to two induction cycles. Secondary endpoints include Overall Survival (OS), defined as the time from study inclusion until death from any cause, and Event Free Survival (EFS), which measures the time from study inclusion until non-achievement of a complete remission at the end of induction, hematological relapse, or death from any cause, whichever occurs first. Relapse Free Survival (RFS) will be evaluated for patients achieving complete remission, measuring the time from remission until hematological relapse or death from any cause.

Additional secondary endpoints include the rate of allogeneic hematopoietic stem cell transplantation and the impact of treatment on quality of life (QoL), assessed using the validated questionnaires EORTC QLQ-C30 and EQ-5D-5L. Adverse events (AEs) and serious adverse events (SAEs) during induction cycle 1, and possibly cycle 2, as well as consolidation cycles, will be collected, graded according to the Common Terminology Criteria for Adverse Events (CTC), and coded using the Medical Dictionary for Regulatory Activities (MEDRA). Incidence proportions of these events will be calculated. The trial is designed to provide comprehensive data on the efficacy of the treatment regimen in patients with newly diagnosed "ELN intermediate or poor-risk" acute myeloid leukemia (AML) intended to undergo allogeneic stem cell transplantation.