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
July 27, 2026 updated by: Fred Hutchinson Cancer Center
Phase 1 Study of FLAG-Ida With Pivekimab Sunirine (PVEK) for Adults With Newly Diagnosed Adverse-Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
OUTLINE: This is a dose-escalation study of PVEK.
INDUCTION THERAPY: Patients receive PVEK intravenously (IV) on day 1 or day 1 and 22. Patients also receive G-CSF subcutaneously (SC) on days 0-5, fludarabine IV over 30 minutes on days 1-5, cytarabine IV over 2 hours on days 1-5, and idarubicin IV on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients who still have cancer after the first cycle of study treatment may receive an additional cycle of induction chemotherapy with PVEK. Patients who go into remission after the first 1 or 2 cycles of study continue to Post-Remission Therapy.
POST-REMISSION THERAPY: Patients receive PVEK IV on day 1 or day 1 and 22 of each cycle and high-dose cytarabine IV every 12 hours on days 1-6 of each cycle. Treatment repeats every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Patients also undergo bone marrow aspiration and may undergo bone marrow biopsy and blood sample collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening and as clinically indicated on trial.
After completion of study treatment, patients are followed every 3 months for 5 years.
Study Type
Interventional
Enrollment (Actual)
30
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Treatment (PVEK, FLAG-Ida)
See Detailed Description.
|
Given IV
Other Names:
Undergo blood sample collection
Other Names:
Given IV
Other Names:
Undergo ECHO
Other Names:
Undergo bone marrow biopsy
Other Names:
Given IV
Other Names:
Undergo MUGA scan
Other Names:
Undergo bone marrow aspirate
Given SC
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of dose-limiting toxicities during cycle 1
Time Frame: During cycle 1 on day 42, or the start of the next cycle
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Incidence of adverse events
Time Frame: Up to 5 years
|
Will be assessed by the NCI CTCAE v.5.
Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
|
Up to 5 years
|
|
Measurable residual disease (MRD) rates
Time Frame: Up to 5 years
|
Will be estimated within the limits of the study with pivekimab sunirine (PVEK) + fludarabine, high-dose cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida) across study cohorts.
Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
|
Up to 5 years
|
|
MRD status
Time Frame: Up to 5 years
|
MRD will be measured by multiparameter flow cytometry.
All positive testing will be considered positive.
|
Up to 5 years
|
|
Relapse-free survival
Time Frame: From the date of achievement of remission until the date of hematologic relapse or death from any cause, assessed up to 5 years
|
Will be assessed within the limits of the study by the relationship between MRD status after induction therapy and relapse risk/time to relapse.
Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
|
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
Time Frame: From day 1 of study treatment to the date of death from any cause, up to 5 years
|
Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
|
From day 1 of study treatment to the date of death from any cause, up to 5 years
|
|
Complete remission rates
Time Frame: Up to 5 years
|
Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
|
Up to 5 years
|
|
Duration of cytopenias
Time Frame: Up to 5 years
|
Will be evaluated by the impact of PVEK dosing regimens on the duration of cytopenias.
Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
|
Up to 5 years
|
|
Proportion of patients receiving allogeneic hematopoietic cell transplantation
Time Frame: Up to 5 years
|
Will be estimated within the limits of the study by the proportion of patients receiving allogeneic HCT in remission with PVEK + FLAG-Ida.
Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data.
|
Up to 5 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Jacob Appelbaum, MD, PhD, Fred Hutch/University of Washington Cancer Consortium
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 18, 2023
Primary Completion (Actual)
May 31, 2026
Study Completion (Estimated)
May 31, 2029
Study Registration Dates
First Submitted
August 18, 2023
First Submitted That Met QC Criteria
September 5, 2023
First Posted (Actual)
September 13, 2023
Study Record Updates
Last Update Posted (Actual)
July 29, 2026
Last Update Submitted That Met QC Criteria
July 27, 2026
Last Verified
July 1, 2026
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Immune System Diseases
- Neoplasms by Histologic Type
- Hematologic Diseases
- Lymphatic Diseases
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Leukemia, Myeloid
- Bone Marrow Diseases
- Leukemia, Lymphoid
- Leukemia
- Hemic and Lymphatic Diseases
- Leukemia, Myeloid, Acute
- Myelodysplastic Syndromes
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Leukemia, Biphenotypic, Acute
- Peptides
- Amino Acids, Peptides, and Proteins
- Proteins
- Organic Chemicals
- Heterocyclic Compounds, 1-Ring
- Heterocyclic Compounds
- Investigative Techniques
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Surgical Procedures, Operative
- Cytological Techniques
- Nucleic Acids, Nucleotides, and Nucleosides
- Cytodiagnosis
- Hydrocarbons
- Hydrocarbons, Cyclic
- Biological Factors
- Carbohydrates
- Polycyclic Aromatic Hydrocarbons
- Hydrocarbons, Aromatic
- Polycyclic Compounds
- Glycosides
- Cytidine
- Pyrimidine Nucleosides
- Pyrimidines
- Diagnostic Techniques, Surgical
- Nucleosides
- Intercellular Signaling Peptides and Proteins
- Arabinonucleosides
- Anthracyclines
- Naphthacenes
- Aminoglycosides
- Glycoproteins
- Glycoconjugates
- Daunorubicin
- Colony-Stimulating Factors
- Hematopoietic Cell Growth Factors
- Cytokines
- Cytarabine
- Idarubicin
- Biopsy
- Specimen Handling
- fludarabine
- Granulocyte Colony-Stimulating Factor
Other Study ID Numbers
- RG1123378 (Fred Hutch/University of Washington Cancer Consortium)
- NCI-2023-03572 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- FHIRB0020122 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
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