Combination Chemotherapy (FLAG-Ida) With Pivekimab Sunirine (PVEK) for the Treatment of Newly Diagnosed Adverse Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms

NCT06034470 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1123378NCI-2023-03572FHIRB0020122
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial finds the best dose of PVEK when given together with fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin, (FLAG-Ida) regimen and studies the effectiveness of this combination therapy in treating patients with newly diagnosed adverse risk acute myeloid leukemia (AML) and other high-grade myeloid neoplasms. PVEK is a monoclonal antibody linked to a chemotherapy drug. PVEK is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD123 receptors, and delivers the chemotherapy drug to kill them. Chemotherapy drugs, such as idarubicin, fludarabine, high-dose cytarabine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. G-CSF helps the bone marrow make more white blood cells in patients with low white blood cell count due to cancer treatment. Giving PVEK with the FLAG-Ida regimen may be a safe and effective treatment for patients with acute myeloid leukemia and other high-grade myeloid neoplasms.

Conditions

Myelodysplastic/Myeloproliferative Neoplasm; Myeloproliferative Neoplasm; Acute Myeloid Leukemia; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities during cycle 1

  Dose-limiting toxicities (DLTs) for trial monitoring are defined as follows: a) Any Grade ≥4 organ toxicity; and b) prolonged severe myelosuppression, as defined by ANC \<500/µL and platelet count \<25,000/µL, for \>42 days after initiation (day 1) of FLAG-Ida chemotherapy in the absence of residual disease (assessed by European LeukemiaNet \[ELN\] response criteria).

  During cycle 1 on day 42, or the start of the next cycle

Secondary Outcomes (8)

• Incidence of adverse events

  Up to 5 years

• Measurable residual disease (MRD) rates

  Up to 5 years

• MRD status

  Up to 5 years

• Relapse-free survival

  From the date of achievement of remission until the date of hematologic relapse or death from any cause, assessed up to 5 years

• Overall survival

  From day 1 of study treatment to the date of death from any cause, up to 5 years

Study Arms (1)

Treatment (PVEK, FLAG-Ida)

EXPERIMENTAL

See Detailed Description.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Cytarabine; Procedure: Echocardiography; Drug: Fludarabine; Drug: Granulocyte Colony-Stimulating Factor; Drug: Idarubicin; Procedure: Multigated Acquisition Scan; Drug: Pivekimab Sunirine

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (PVEK, FLAG-Ida)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspirate

Treatment (PVEK, FLAG-Ida)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (PVEK, FLAG-Ida)

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (PVEK, FLAG-Ida)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (PVEK, FLAG-Ida)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (PVEK, FLAG-Ida)

Granulocyte Colony-Stimulating Factor DRUG

Given SC

Also known as: Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, Granulocyte Colony Stimulating Factor, Pluripoietin

Treatment (PVEK, FLAG-Ida)

Idarubicin DRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-Demethoxydaunorubicin, 4-DMDR

Treatment (PVEK, FLAG-Ida)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (PVEK, FLAG-Ida)

Pivekimab Sunirine DRUG

Given IV

Also known as: Anti-CD123 ADC IMGN632, Antibody-drug Conjugate IMGN632, CD123-targeted ADC IMGN632, IMGN 632, IMGN-632, IMGN632

Treatment (PVEK, FLAG-Ida)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Diagnosis of untreated AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 5th edition of the World Health Organization (WHO) classification of hematolymphoid tumors. Patients with myelodysplastic, myeloproliferative, or myelodysplastic/myeloproliferative neoplasms and ≥ 10% blasts in blood and/or bone marrow, are also eligible, as are patients with mixed phenotype acute leukemia (MPAL). Outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered. Diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate
• Cytogenetically/molecularly adverse-risk disease (European LeukemiaNet \[ELN\] 2022 criteria)
• Expression of CD123 on immunophenotypically abnormal blasts, as assessed by local multiparameter flow cytometry. Evaluation of CD123 expression via immunohistochemistry is permissible, for example if flow cytometric assessment is not available
• Medically fit, as defined by treatment-related mortality (TRM) score ≤ 13.1 calculated with simplified model
• The use of hydroxyurea prior to start of study therapy is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood cell count (WBC) \> 100,000/μL or with concern for other complications of high tumor burden (e.g. disseminated intravascular coagulation) can be treated with leukapheresis prior to start of study therapy
• Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. \< 10% blasts in blood and bone marrow)
• Bilirubin =\< 1.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x IULN unless elevation is thought to be due to hepatic infiltration by AML
• Creatinine clearance \>= 60 mL/min
• Left ventricular ejection fraction \>= 45%, assessed by multigated acquisition (MUGA) scan or echocardiography or other appropriate diagnostic modality and no clinical evidence of congestive heart failure
• Fertile male and female subjects must be willing to use an effective contraceptive method before, during, and for at least 3 months after receiving the investigational agent
• Provide written informed consent

You may not qualify if:

• Diagnosis of blast phase chronic myeloid leukemia (CML)
• Patients with FLT3-mutated AML
• Concomitant illness associated with a likely survival of \< 1 year
• Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with antimicrobials, and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired \[e.g. known chronic viral hepatitis, human immunodeficiency virus (HIV)\]). Patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours. Patients with fever thought to be likely secondary to leukemia are eligible
• Known hypersensitivity to any study drug or prior \>= grade 3 hypersensitivity reactions to monoclonal antibodies
• Confirmed or suspected pregnancy or active breast feeding
• Treatment with any other investigational anti-leukemia agent

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• AbbVie: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders

Interventions

Specimen Handling; Biopsy; Cytarabine; fludarabine; Granulocyte Colony-Stimulating Factor; Idarubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides

Study Officials

• Jacob Appelbaum, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2023
• First Posted: September 13, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2029
• Last Updated: May 7, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)