GTB-3550 Tri-Specific Killer Engager (TriKE®) for High Risk Hematological Malignancies

Inclusion Criteria: Eligible Diseases * 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 (IPSS-R) High or Very High Risks * World Health Organization (WHO) Classification: Refractory anemia with excess blasts-1 (RAEB-1) or RAEB-2 * Poor and very-poor risk cytogenetic abnormality as defined by the IPSS-R cytogenetic classifications * WHO Based Prognostic Scoring System (WPSS): High or Very High Risk * Therapy related MDS and not a candidate for induction chemotherapy or had an inadequate treatment response after induction chemotherapy. * 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 hematopoietic stem cell transplant (HSCT), at least one re-induction attempt required * Prior HSCT relapse beyond 3 months may be included only if off immunosuppression for a minimum of 4 weeks and do not have graft-versus-host disease (GVHD) * 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. Inclusion Criteria: Age, Performance Status, Organ Function, Contraception Use * At least 18 years of age * Karnofsky score ≥ 70% * Adequate organ function within 14 days (30 days for cardiac and pulmonary) of study enrollment defined as: * Renal: an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 * Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and total bilirubin within normal range * Pulmonary function: Diffusing capacity 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 \[CTCAE\] v5 Grade 1 carbon monoxide diffusing capacity decreased) based on patient's height, weight, and gender as reported by the institutional pulmonary function lab. * Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia; left ventricular ejection fraction ≥ 45% by echocardiogram, multigated acquisition (MUGA) scan or cardiac MRI. * Absolute lymphocyte count (ALC) ≥ 200 cells/mm³ OR absolute circulating CD56+/CD3- NK cell count \>25 cells/μl 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 computerized 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, known history of 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, 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 GTB-3550 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 within a 90 minute drive of the study center through at least Day 29