Combination chemotherapy with a targeted therapy for newly diagnosed high-risk acute myeloid leukemia
Phase 1 Study of FLAG-Ida With Pivekimab Sunirine (PVEK [IMGN632]) for Adults With Newly Diagnosed Adverse-Risk Acute Myeloid Leukemia and Other High-Grade Myeloid Neoplasms
This study is testing a new combination of a targeted therapy and chemotherapy to see if it helps people with newly diagnosed high-risk acute myeloid leukemia feel better and improve their chances of recovery.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Fred Hutchinson Cancer Center Academic / other |
| Drugs / interventions | chemotherapy, fludarabine |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT06034470 on ClinicalTrials.gov |
What this trial studies
This phase I trial aims to determine the optimal dose of Pivekimab Sunirine (PVEK) when combined with the FLAG-Ida chemotherapy regimen for patients with newly diagnosed adverse risk acute myeloid leukemia (AML) and other high-grade myeloid neoplasms. The study evaluates the effectiveness of this combination therapy, which includes a monoclonal antibody that targets CD123 receptors on cancer cells, delivering chemotherapy directly to them. Patients will receive PVEK alongside standard chemotherapy agents and will be monitored for disease progression and treatment toxicity. The trial also includes follow-up assessments for up to five years post-treatment.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older with newly diagnosed adverse risk acute myeloid leukemia or other specified high-grade myeloid neoplasms.
Not a fit: Patients with acute promyelocytic leukemia or those without the CD123 receptor expression may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could improve outcomes for patients with high-risk acute myeloid leukemia by providing a more effective targeted therapy option.
How similar studies have performed: Other studies have shown promise with similar targeted therapies in treating acute myeloid leukemia, suggesting potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Seattle, Washington
- Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)
Study contacts
- Principal investigator: Jacob Appelbaum, MD, PhD — Fred Hutch/University of Washington Cancer Consortium
- Study coordinator: Jacob Appelbaum, MD, PhD
- Email: jappelb@uw.edu
- Phone: 206-314-2788
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.