A Specialized Protein (161533 TriKe) in Treating Patients with High Risk Myelodysplastic Syndromes, Refractory or Relapsed Acute Myeloid Leukemia or Advanced Systemic Mastocytosis

Inclusion Criteria

• Diagnosis of one of the following CD33-expressing myeloid malignancies with greater than or equal to 50% CD33+ target cells with no good standard of care treatment options including: * High risk myelodysplastic syndromes (MDS) progressive on two or more prior regimens and requiring treatment that meets at least one of the following: ** Revised International Prognostic Scoring System (R-IPSS) category: INT-2 or high risk ** R-IPSS high or very high risks ** World Health Organization (WHO) classification: RAEB-1 or RAEB-2 ** Poor and very-poor risk cytogenetic abnormality as defined by the R-IPSS cytogenetic classifications ** WHO Based Prognostic Scoring System (WPSS): High or very high risk * Therapy related MDS and not a candidate for induction chemotherapy. Would be eligible if treated with induction chemotherapy and had an inadequate treatment response
• Refractory or relapsed acute myelogenous leukemia (AML) meeting at least one of the following: * Refractory AML defined as failure to achieve remission after at least 3 induction attempts ** Elderly AML not fit for induction therapy can be enrolled after 2 failed inductions * Relapsed AML ** Not a candidate for stem cell transplant (HSCT), at least one re-induction attempt required ** Prior HSCT relapse beyond 12 months without active graft versus host disease (GVHD) requiring systemic steroids, at least one re induction attempt required * Notes: ** For hypomethylating agents (i.e. decitabine, azacitidine) to count as an induction/re-induction attempt, the patient must have completed a minimum of 3 monthly cycles ** For targeting agents (i.e. sorafenib) to count as an induction/re-induction attempt, the patient must have completed a minimum of 1 month without attaining complete remission (CR)
• Advanced systemic mastocytosis (defined as mast cell leukemia, aggressive systemic mastocytosis, and systemic mastocytosis associated with hematologic neoplasm) may enroll without any prior treatment, given there is no standard established therapy
• At least 18 years of age
• Karnofsky score >= 70%
• Estimated glomerular filtration rate >= 60 mL/min/1.73 m^2 using Modification of Diet in Renal Disease equation (within 14 days of study enrollment)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) within normal range (within 14 days of study enrollment)
• Alkaline phosphatase within normal range (within 14 days of study enrollment)
• Total bilirubin within normal range (within 14 days of study enrollment)
• Diffusing capacity of the lungs for carbon monoxide (DLCO) corrected (ml/min/mm Hg) defined as no more than 5 units below lower limit of normal (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5 Grade 1 carbon monoxide diffusing capacity decreased) based on patient’s height, weight, and gender as reported by the institutional pulmonary function lab (within 30 days of study enrollment)
• Absence of decompensated congestive heart failure, or uncontrolled arrhythmia; left ventricular ejection fraction >= 45% by echocardiogram, multigated acquisition scan (MUGA) or cardiac magnetic resonance imaging (MRI) (within 30 days of study enrollment)
• Absolute lymphocyte count (ALC) >= 200 cells/mm^3 OR absolute circulating CD56+/CD3- NK cell count > 25 cells/ul (within the 14 days prior to start of therapy)
• Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment
• Participant provides voluntary written consent signed before performance of any study-related procedure not part of normal medical care

Exclusion Criteria

• New or progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (CT) scan unless cleared for study by pulmonary; infiltrates attributed to infection must be stable/improving with associated clinical improvement after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections)
• Uncontrolled bacterial, fungal or viral infections including human immunodeficiency virus (HIV)
• Active hepatitis B or hepatitis C (virus detectable by polymerase chain reaction [PCR]) - chronic asymptomatic viral hepatitis is allowed
• Other concurrent active cancer within the last year (excluding non-melanoma skin cancers)
• Severely clinically obese patients, body mass index (BMI) > 38
• Currently taking any over-the-counter (OTC), vitamin, mineral, or dietary supplement within 14 days prior to study drug administration on day 1 and during study conduct that may confound study safety goals (e.g. St. John’s wort). Questions should be discussed with GT Biopharma
• Pregnant or breast feeding. The effect of 161533 TriKE on the fetus is unknown. Females of childbearing potential must have a blood test within 7 days prior to enrollment to rule out pregnancy - must be repeated if not within 7 days of treatment initiation
• History of central nervous system (CNS) malignancy or symptoms of active CNS disease
• A family history of long QT syndrome or with a corrected QT (QTc) interval > 480 msec at screening
• Currently taking medications known to prolong QT/QTc interval as the potential risk of QT/QTc prolongation is unknown in humans
• A candidate for potentially curative therapy, including hematopoietic cell transplant
• Unwilling to remain in the greater Twin Cities metropolitan area through at least day 29