Preemptive CIML NK Cell Therapy After Hematopoietic Stem Cell Transplantation

Exclusion Criteria

• •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
• •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.
• •Extramedullary leukemia involving sanctuary sites not readily accessible to immune surveillance, such as CNS or testis. Other sites of extramedullary relapse (e.g., leukemia cutis, granulocytic sarcoma) are acceptable.
• •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 PI.
• •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.
• •Prior history of solid organ (allograft) transplantation
• •Prior history of allergic reactions to cellular products
• •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.
• •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.
• •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.
• •Patients with active and uncontrolled Hepatitis B or C are ineligible due to the high risk of treatment-related hepatotoxicity after cellular therapy.
• •Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1. History of other malignancy and have had complete remission of disease for at least 2 years; 2. 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.
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in study. 3. Diagnosed with MGUS or smoldering myeloma, and/or treated for multiple myeloma or plasmacytoma as long as attainment of complete remission by IMWG criteria following therapy.
• •Prior history of Grade 2 or higher hemolytic anemia (\>/= 2g decrease in hemoglobin plus laboratory evidence of hemolysis) from any cause.
• •Systemic steroid therapy (oral or IV) on the day of NK cell infusion
• •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.
• •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 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 CRS excludes patients if they are still on steroids by the day of planned NK cell infusion.
• •Patients must be off systemic steroid therapy on the day of planned NK cell 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.