Tagraxofusp to Eradicate Measurable Residual Disease in Patients With Acute Myeloid Leukemia

This phase Ib/II trial tests the safety of tagraxofusp when given with or without azacitidine in patients with acute myeloid leukemia in remission with measurable residual disease who will undergo allogeneic hematopoietic cell transplant. Tagraxofusp is a recombinant protein consisting of IL-3 conjugated to a truncated diptheria toxin. The IL-3 attaches to the cancer cells and the toxic substance kills them. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Tagraxofusp and azacitidine may work better to kill cancer cells and eradicate measurable residual disease in patients with acute myeloid leukemia.

Inclusion Criteria:Age >= 18 yearsAML in first or second remission, including:Complete remission (CR), defined as bone marrow blasts < 5%, absence of circulating blasts, absence of extramedullary disease, absolute neutrophil count (ANC) >= 1,000/uL, platelet count > 100,000/uLComplete remission with incomplete hematologic recovery (CRi), defined as all CR criteria except for residual neutropenia (ANC < 1,000/uL) or residual thrombocytopenia (platelet count < 100,000/uL)Morphologic leukemia-free state with adequate marrow recovery, defined as bone marrow blasts < 5%, ANC >= 500/uL, and platelet count >= 20,000/uLMinimal residual disease positive >= 0.01% based on MPFCFor participants in first remission, MRD positivity at any point from time of establishing first remission onward while still in first remissionFor participants in second remission, MRD positivity at any point from time of establishing second remission onward while still in second remissionMRD must be repeated and remain positive if additional treatment is given prior to enrollmentCD123 positivity on flow cytometry (partial, dim, or bright) from either:Conventional flow cytometry on marrow specimen from time of original diagnosis or first relapseHigh-sensitivity multiparametric flow cytometry on marrow specimen from time of MRD positivityEastern Cooperative Oncology Group (ECOG) 0-2Serum albumin level >= 3.2 g/dL in the absence of receiving albumin infusionSerum total bilirubin =< 1.5 mg/dL, unless considered due to Gilbert's disease or medication effectAspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase =< 2.5 times the upper limit of normal, unless considered due to medication effect (eg, azole therapy)Creatinine clearance >= 60 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR) and serum creatinine (Cr) =< 1.8 mg/dLAbility to give full informed consentFemales of reproductive potential (postmenopausal for less than 24 consecutive months) must have a negative pregnancy test within 1 week of initiating treatment and may not be breastfeedingExclusion Criteria:MRD negativity < 0.01% at screeningIntensive AML therapy within the past 14 days, or non-intensive targeted therapy within the past 7 daysCord blood as donor sourceSecond malignancy that would be expected to limit survival within less than 2 yearsCardiovascular disease that would result in high risk for toxicity, including:Uncontrolled or New York Heart Association (NYHA) class III or VI congestive heart failureRecurrent or uncontrolled anginaUnstable angina, myocardial infarction, or stroke in past 6 monthsUncontrolled hypertensionArrhythmia not controlled by medicationLeft ventricular ejection fraction < 50%History of coronary stent placement that requires mandatory continuation of dual antiplatelet therapyUncontrolled intercurrent illness that includes but is not limited to: uncontrolled infection, disseminated intravascular coagulation, psychiatric illness/compliance issues that would limit compliance with study protocolAny medical condition that in the opinion of the investigator places the participant at unacceptable risk for toxicity to investigational therapy