Cytokine-Induced Memory-Like Natural Killer Cell Therapy with interlekin-2 after Hematopoietic Stem Cell Transplantation for the Treatment of Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome with Measurable Residual Disease

Inclusion Criteria

• TRIAL ENROLLMENT: Histologically or cytologically confirmed diagnosis of AML, MDS, or myelodysplastic syndrome/myeloprolific neoplasm (MDS/MPN) that is at high risk for post-transplant relapse and that has measurable disease prior to transplant. * Patients at high risk for post-transplant relapse include: ** De novo AML diagnosed at or after age 60, except core binding factor (CBF) AML ** De novo AML in CR1 ** Secondary AML ** Any AML transplanted in CR2 or greater ** TP53-mutated MDS or AML ** Therapy-related MDS or AML ** MDS with monosomy 7 ** MDS with >= 10% blasts at the time of transplant ** MDS/MPN or chronic myelomonocytic leukemia (CMML) * Minimal residual disease on most recent pre-transplant bone marrow is defined by next-generation duplex sequencing with the Rapid Heme panel
• TRIAL ENROLLMENT: Total bilirubin: ≤ 1.5 x institutional upper limit of normal (ULN) (except Gilbert’s or disease related hemolysis, then < 3 x ULN)
• TRIAL ENROLLMENT: Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN
• TRIAL ENROLLMENT: Serum creatinine ≤ 2.0mg/dL
• TRIAL ENROLLMENT: oxygen (O2) saturation: ≥ 90% on room air
• TRIAL ENROLLMENT: Left ventricular ejection fraction (LVEF) > 40%. If there is no clinical evidence of a change in cardiovascular function from the time of pre-transplantation ECHO (per Foundation for the Accreditation of Cellular Therapy [FACT] standards should be performed within 6 weeks of stem cell infusion), then there is no need to repeat it. Otherwise, an ECHO will need to be repeated
• TRIAL ENROLLMENT: Adult patients (age ≥ 18) eligible for and planned to undergo a standard-of-care reduced intensity conditioning (RIC) HLA-matched related or related haploidentical allogeneic stem cell transplant using PTCY-based GVHD prophylaxis. All eligibility criteria and workups for undergoing standard of care (SOC) allogeneic SCT for the recipient and donor will be based on institutional standards and standard operating procedures (SOPs)
• TRIAL ENROLLMENT: For patients with AML, the disease must meet criteria for CR/Cri according to 2017 European Leukemia Net (ELN) guidelines. For patients with MDS and MDS/MPN patients, the blast percentage on the bone marrow aspirate and biopsy must be less than 10%
• TRIAL ENROLLMENT: The same related donor is available to provide a non-mobilized apheresis product after the stem-cell donation
• TRIAL ENROLLMENT: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• TRIAL ENROLLMENT: Negative pregnancy test for women of childbearing age
• TRIAL ENROLLMENT: The effects of CIML NK cells combined with IL-2 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after IL-2 dose administration
• TRIAL ENROLLMENT: No laboratory evidence of ongoing hemolysis in opinion of investigator
• CIML NK INFUSION: Total bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert’s then < 3 x ULN) within 24 hours of NK cell infusion
• CIML NK INFUSION: AST(SGOT)/ALT(SGPT): ≤ 3 x institutional ULN within 24 hours of NK cell infusion
• CIML NK INFUSION: Grade ≥ 3 non-hematologic toxicities of transplant conditioning (except for grade 3 nausea, vomiting, diarrhea, or constipation) within 24 hours of NK cell infusion
• CIML NK INFUSION: No significant change in clinical status that would, in the opinion of the investigator, increase the risk of adverse events associated with CIML NK infusion, (e.g., symptomatic congestive heart failure, unstable angina, cardiac arrhythmia)
• CIML NK INFUSION: No evidence of ongoing hemolysis for any reason in opinion of investigator
• CIML NK INFUSION: Participants who have had other investigational agents within 4 weeks prior to CIML NK cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 8 weeks prior, or those who have not recovered from adverse events due to agents administered more than 4 weeks prior. Therapy with BCR-ABL inhibitors must be stopped at least 2 weeks before CIML NK cell infusion and may not be resumed during the dose limiting toxicity (DLT) period. The use of tocilizumab for cytokine release syndrome after stem cell infusion does not exclude patients, but the use of steroids for the treatment of cytokine release syndrome (CRS) excludes patients if they are still on steroids by the day of planned NK cell infusion

Exclusion Criteria

• TRIAL ENROLLMENT: Adult participants who are eligible for and who would be expected to have a greater benefit from myeloablative conditioning in their SOC allo HSCT as judged by their treating physician
• TRIAL ENROLLMENT: Participants with mutations such as FLT3-ITD, IDH, or BCR-ABL mutations who are planned to receive targeted agent maintenance therapy to prevent relapse post-transplant are excluded
• TRIAL ENROLLMENT: Extramedullary leukemia involving sanctuary sites not readily accessible to immune surveillance, such as central nervous system (CNS) or testis. Other sites of extramedullary relapse (e.g., leukemia cutis, granulocytic sarcoma) are acceptable
• TRIAL ENROLLMENT: The planned use of sirolimus for GVHD prophylaxis would result in exclusion of the patient from the study. Consideration of the addition of sirolimus to the GVHD prophylaxis regimen within the first 100 days after transplant must be reviewed with the study primary investigator (PI)
• TRIAL ENROLLMENT: Prior history of allogeneic stem cell transplant other than SOC alloHSCT referred to in this study taking place 7 days prior to CIML NK infusion
• TRIAL ENROLLMENT: Prior history of solid organ (allograft) transplantation
• TRIAL ENROLLMENT: Prior history of allergic reactions to cellular products
• TRIAL ENROLLMENT: Uncontrolled concurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social illness that would limit compliance with study requirements
• TRIAL ENROLLMENT: Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and IL-2 and with the potential for teratogenic or abortifacient effects by Flu/Cy chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and IL-2, breastfeeding should be discontinued if the mother is treated on this study
• TRIAL ENROLLMENT: HIV-positive patients are excluded due to the potential for interaction between antiretroviral therapy as well as the risk for lethal infection in the context of marrow-suppressive therapy
• TRIAL ENROLLMENT: Patients with active and uncontrolled hepatitis B or C are ineligible due to the high risk of treatment-related hepatotoxicity after cellular therapy
• TRIAL ENROLLMENT: Individuals with a history of a different malignancy are ineligible except for the following circumstances: * History of other malignancy and have had complete remission of disease for at least 2 years; * Diagnosed and treated within the past 2 years for: nonmetastatic melanoma, surgically resected (not needing systemic chemotherapy) squamous cell carcinoma of skin and nonmetastatic prostate cancer not needing systemic chemotherapy * Diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma, and/or treated for multiple myeloma or plasmacytoma as long as attainment of complete remission by International Myeloma Working Group (IMWG) criteria following therapy
• TRIAL ENROLLMENT: History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in study
• TRIAL ENROLLMENT: Prior history of grade 2 or higher hemolytic anemia (>/= 2g decrease in hemoglobin plus laboratory evidence of hemolysis) from any cause
• CIML NK INFUSION: Uncontrolled concurrent illness such as ongoing or active infection
• CIML NK INFUSION: Systemic steroid use of ≥ 10mg/day of prednisone or equivalent for 4 weeks prior to CIML NK infusion. Patients must be off systemic steroid therapy on the day of planned NK cell infusion
• CIML NK INFUSION: The presence of donor-specific antibodies (DSAs) with mean fluorescence intensity (MFI) >1000 using a standard assay who do not receive a desensitization protocol prior to and during stem cell transplant, or else who do receive a desensitization protocol and have detectable DSAs +1 day after stem cell infusion