Natural Killer Cells KDS-1001 to Decrease Disease Relapse in Patients with High-Risk Myeloid Malignancies Undergoing Donor Stem-Cell Transplants

Inclusion Criteria

• Patients ages 18 to 70 years old at the time of enrollment
• Patients weighing at least 42 kg
• Patient with the hematologic malignancies described below, as well as an human leukocyte antigen (HLA) matched related donor, HLA matched unrelated donor, a haploidentical related donor, or a one antigen mismatched unrelated donor. HLA matching includes HLA A, B, C, and DR-B1
• Patients must have one of the following diseases: * Acute myeloid leukemia (AML): ** First complete remission with high-risk features defined as: *** Greater than 1 cycle of induction therapy required to achieve remission; *** Preceding myelodysplastic syndrome (MDS); *** Presence of FLT3 mutations or internal tandem duplication or other mutations designated as adverse-risk by the European LeukemiaNet (ELN) criteria. *** Adverse: **** t(6;9)(p23;q34.1); DEK-NUP214 **** t(v;11q23.3); KMT2A rearranged **** t(9;22)(q34.1;q11.2); BCR-ABL1 **** inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1) **** -5 or del(5q); -7; -17/abn(17p) **** Complex karyotype, monosomal karyotype **** Wild-type NPM1 and FLT3-ITDhigh **** Mutated RUNX1 **** Mutated ASXL1 **** Mutated TP53 *** French-American-British (FAB) M6 or M7 classification; *** Adverse cytogenetics: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype [> 3 abnormalities]; or other mutations designated as adverse-risk by the ELN criteria; *** Treatment-related AML *** Primary induction failure with partial response to therapy who achieve adequate cytoreduction, or *** Aplastic/hypoplastic marrow with or without detectable persistent disease after induction chemotherapy or after salvage chemotherapy. ** Patients must be in: *** CR: complete remission, *** CRi: CR with incomplete hematologic recovery, or *** MLFS: morphological leukemia-free state with less than 5% bone marrow blasts * Patients cannot be beyond CR 3, i.e., have relapsed more than 2 times * Myelodysplastic syndromes (MDS): ** De novo MDS with intermediate or high-risk International Prognostic Scoring System (IPSS) scores. Patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy, or patients with treatment-related MDS. Patients must have less than 10% bone marrow blasts * Chronic myeloid leukemia (CML): ** Failed to achieve cytogenetic remission or have cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or ** Accelerated phase or blast phase at any time. ** Intolerant of available tyrosine kinase inhibitors (TKIs)
• Performance score of at least 70% by Karnofsky or 0 to 1 by Eastern Cooperative Oncology Group (ECOG)
• Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockcroft-Gault formula)
• Bilirubin equal or less than 1.5 mg/dl except for Gilbert’s disease. Conjugated (direct) bilirubin less than 2x upper limit of normal.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal or less than 200 U/L for adults
• Left ventricular ejection fraction equal or greater than 45%
• Diffusing capacity for carbon monoxide (DLCO) equal or greater than 60% predicted corrected for hemoglobin
• Ability to understand and willingness to sign the written informed consent document
• Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator while on study

Exclusion Criteria

• Human immunodeficiency virus (HIV) positive; active hepatitis B or C
• Uncontrolled infections; principal investigator (PI) is the final arbiter of this criterion
• Liver cirrhosis
• Central nervous system (CNS) involvement within 3 months prior to the transplant
• Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
• Inability to comply with medical therapy or follow-up
• Patient with a known history of allergic reactions to any constituents of the product, including a known history of allergic reactions to cellular products or dimethyl sulfoxide (DMSO)
• Prior allogeneic SCT
• Other malignancy/cancer diagnosis < 2 years ago, not including nonmelanoma skin cancer
• Requiring systemic corticosteroids with prednisone dose > 10 mg or equivalent
• KDS-1001 donor specific antibodies (dsa) > 5000 melt flow index (MFI) units
• KDS-1001 donor anti-C1q positive