Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment

Inclusion Criteria: * Patients must have histologically or cytologically confirmed diagnosis of MDS by bone marrow biopsy by World Health Organization (2016) guidelines * Patients with MDS who have progressed or had no response after 6 cycles of azacitidine or 4 cycles of decitabine * For the expansion phase, we will be enrolling 12 more patients at the maximum tolerated dose: 6 patients with prior azacitidine or decitabine treatment and 6 patients with prior treatment with azacitidine or decitabine in combination with venetoclax * Patients with MDS must have ≥ 5% myeloblasts * Patients with demonstration of CD33 positive myeloblasts on flow cytometry using Phycoerythrin (PE) labeled anti-CD33 antibody, done as standard of care testing by every participating site * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of lintuzumab-Ac225 in patients \< 18 years of age, children are excluded from this study * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%) * Serum direct bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN * Creatinine clearance ≥ 50mL/min (Cockcroft-Gault equation) * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better * The effects of lintuzumab-Ac225 on the developing human fetus are unknown. For this reason and because CD33 radiotherapy agents are known to be teratogenic, female patients of childbearing age must have had a negative serum pregnancy test within 14 days of initiation of dosing and must agree to use of two acceptable methods of birth control while on the study drug. A woman must agree to remain on a highly effective method throughout the study and for at least 6 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. During the study and for 30 days after receiving the last dose of study drug in addition to the highly effective method of contraception, a man (a) who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (e.g. condom with spermicidal foam/gel/film/cream/suppository); (b) who is sexually active with a woman who is pregnant must use a condom; (c) must agree not to donate sperm * Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants Exclusion Criteria: * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Patients have active clinically significant graft vs. host disease (GVHD) or are on systemic corticosteroids * Patients have clinically active central nervous system (CNS) leukemia * Patients who are receiving any other investigational agents, such as experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is shorter, prior to enrollment, or is currently enrolled in any other type of medical research (e.g. medical device) not scientifically or medically compatible with this study * Patients who are receiving any therapy that can result in increased toxicity on this study or confound the study findings, within the last 30 days or 5 half-lives, whichever is shorter, prior to enrollment * History of allergic reactions attributed to compounds of similar chemical or biologic composition to lintuzumab-Ac225 * Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make this protocol unreasonably hazardous * Pregnant women are excluded from this study because lintuzumab-Ac225 is a CD33 radiotherapy agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lintuzumab-Ac225, breastfeeding should be discontinued if the mother is treated with lintuzumab-Ac225 * The patient had major surgery within 14 days prior to enrollment * No prior radiopharmaceutical therapy and no radiation therapy within the last 120 days prior to cycle 1 day 1 (C1D1), as this may contribute to added toxicity * Patients who are unable to take spironolactone or eplerenone due to intolerance, allergy, drug-drug interactions, or for any other reason