Magrolimab Plus Intensive Chemotherapy in Newly Diagnosed AML or HR-MDS

NCT05829434 | Withdrawn Phase 2

• 2 other identifiers: MAGROLICEU Trial Number
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Use of magrolimab in combination with standard intensive chemotherapy ("7+3" or CPX-351) in newly diagnosed "ELN 2022 intermediate or adverse-risk" AML or high risk MDS patients, who intend to undergo allogeneic stem cell transplantation

Conditions

Acute Myeloid Leukemia; Myelodysplastic Neoplasm

Keywords

AML; Hihg-risk MDS

Outcome Measures

Primary Outcomes (1)

• Best CR/CRi/CRh

  Analysis of best CR/CRi/CRh (taken into count: number of neutrophils, platelets and bone marrow blasts) to describe efficacy of magrolimab in combination with intensive chemotherapy

  Up to 28 days

Secondary Outcomes (7)

• Overall Survival

  up to 28 months

• Event Free Survival

  up to 57 days

• Relapse Free Survival

  up to 28 months

• Rate of allo HSCT

  up to 28 days

• Quality of life (EORTC QLQ-C30)

  up to 4 months

Study Arms (2)

Magrolimab + intensive chemotherapy (7+3)

EXPERIMENTAL

Patients will receive magrolimab in combination with "7+3"

Drug: Magrolimab; Drug: 7+3

Magrolimab + intensive chemotherapy (CPX-351)

EXPERIMENTAL

Patients will receive magrolimab in combination with CPX-351

Drug: Magrolimab; Drug: CPX-351

Interventions

Magrolimab DRUG

Patients will receive magrolimab on day 1; 4: IV 1 mg/kg; day 8: IV 15 mg/kg; day 11, 15 and 22: IV 30 mg/kg (plus 30 mg/kg for 5 weeks weekly and then q2w until the end of consolidation)

Also known as: Hu5F9-G4, GS-4721

Magrolimab + intensive chemotherapy (7+3); Magrolimab + intensive chemotherapy (CPX-351)

7+3 DRUG

Patients will receive during Induction cycle 1: cytarabine at 100 mg/m² on study days 1-7 as a continuous infusion over 22-24 hours and daunorubicin at 60 mg/m² on study days 3, 4, 5 * optional during Induction cycle 2: cytarabine at 100 mg/m² on days 1-7 of the second induction cycle (i.e. study days 29-35) as a continuous infusion over 22-24 hours and daunorubicin at 60 mg/m² on days 3, 4, 5 of the second induction cycle (i.e. study days 31, 32, 33) * optional during Consolidation cycle: cytarabine at 1 g/m² administered on days 1, 3, 5 of each consolidation cycle as an infusion for 2 hours every 12 hours (for patients \< 60 years up to 3 CONS cycles and for patients ≥ 60 years up to 2 CONS cycles)

Also known as: Daunorubicine and Cytarabine

Magrolimab + intensive chemotherapy (7+3)

CPX-351 DRUG

Patients will receive during Induction cycle 1: CPX-351 with daunorubicin 44 mg/m² and cytarabine 100 mg/m² on days 1, 3, 5 * optional during Induction cycle 2: CPX-351 with daunorubicin 44 mg/m² and cytarabine 100 mg/m² on days 29 + 30 * optional during Consolidation cycle: CPX-351 with daunorubicin 29 mg/m² and cytarabine 65 mg/m² on days 1, 3

Also known as: Vyxeos®

Magrolimab + intensive chemotherapy (CPX-351)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AML or MDS-IB2 according to WHO 2022 criteria
• For both MDS and AML: "Intermediate" or "adverse risk" genetic changes according to ELN 2022 category
• Eligible for and intention to undergo intensive chemotherapy (IC) (CPX-351 or "7+3") followed by allogeneic HSCT, as judged by the investigator

You may not qualify if:

• Patients harboring a FLT3mut, regardless of FLT3-ITD or FLT3-TKD mutation status and intended to receive midostaurin during induction and consolidation
• Patients intended to receive gemtuzumab-ozogamicin during intensive chemotherapy
• Patient does not accept bone marrow sampling during screening, during and after the treatment
• Patient does not accept several blood samplings during screening, treatment and after the treatment
• Patients who are not eligible for standard intensive chemotherapy as assessed by the treating physician
• Previous anthracycline-containing chemotherapy (Exception: cumulative dose for 1 cycle of planned induction therapy (CPX-351 or "7+3") not reached)
• Any prior treatment for AML or MDS (except for hydroxyurea or treatment for low-risk MDS e.g. growth factors) or prior treatment with CD47 or SIRPα-targeting agents, including magrolimab
• Inadequate organ function as defined as any criterion in the list below:
• Congestive heart failure or documented cardiomyopathy with an EF ≤50%
• Documented pulmonary disease with DLCO ≤65% or FEV1 ≤65%, or dyspnea at rest or requiring oxygen, or any pleural neoplasm or uncontrolled lung neoplasm
• On dialysis and age older than 60 years or uncontrolled renal carcinoma
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) \> 5× upper limit of normal (ULN) or liver cirrhosis Child B or C or any biliary tree carcinoma or uncontrolled liver carcinoma or acute viral hepatitis
• Bilirubin \> 1.5× ULN, or 3.0× ULN and primarily unconjugated if patient has a documented history of Gilbert's syndrome or genetic equivalent
• Serum creatinine \> 1.5× ULN or calculated glomerular filtration rate (GFR) \< 40 mL/min/1.73 m²
• ECOG performance status of ≥ 3

Sponsors & Collaborators

• Uwe Platzbecker: lead
• Gilead Sciences: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

magrolimab; Daunorubicin; Cytarabine; CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia; Myelodysplastic Syndromes; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Uwe Platzbecker, Prof. Dr.

  University of Leipzig

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical professor

Model Details: Patients are either treated with CPX-351 or 7+3

Study Record Dates

• First Submitted: March 22, 2023
• First Posted: April 25, 2023
• Study Start: March 31, 2024
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): August 30, 2029
• Last Updated: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share