Off-the-shelf NK Cells + SCT for Myeloid Malignancies

Inclusion Criteria

• •1. Patients ages 18 to 70 years old at the time of enrollment.
• •2. Patients weighing at least 42 kg
• •3. Patient with the hematologic malignancies described below, as well as an 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.
• •4. Patients must have one of the following diseases:
• •Acute myeloid leukemia (AML):
• •a. With one or more high-risk features defined as: (i) Greater than 1 cycle of induction therapy required to achieve remission; (ii) Preceding myelodysplastic syndrome (MDS);
• •Presence of FLT3 mutations or internal tandem duplication or other mutations designated as adverse-risk by the ELN Leukemia Net AML Classification (see Appendix 2):
• •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 (iv) FAB M6 or M7 classification; (v) 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; (vi) Treatment-related AML (vii) Primary induction failure with partial response to therapy who achieve adequate cytoreduction (viii) Aplastic/hypoplastic marrow with or without detectable persistent disease after induction chemotherapy or after salvage chemotherapy.
• •(ix) Have minimal residual disease by flow cytometry, FISH, detection of disease related mutations or cytogenetic abnormality after first course of induction chemotherapy (x) Have relapsed after prior allogeneic hematopoietic transplant
• •AND
• •b. Patients must be in one of the following (i) CR: complete remission, (ii) CRi: CR with incomplete hematologic recovery, or (iii) MLFS: morphological leukemia-free state with less than 5% bone marrow blasts.
• •(iv) If not in either of the above i-iii, then may be in either of the following:
• •1. Primary induction failure with partial response to therapy who achieve adequate cytoreduction
• •2. Aplastic/hypoplastic marrow with or without detectable persistent disease after induction chemotherapy or after salvage chemotherapy
• •Myelodysplastic syndromes (MDS):
• •a. De novo MDS with intermediate or high-risk IPSS scores, chronic myelomonocytic leukemia (CMML) or treatment-related MDS. Patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy. .
• •Patients must have less than 10% bone marrow blasts
• •Chronic myeloid leukemia (CML):
• •1. Failed to achieve cytogenetic remission or have cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or
• •2. Accelerated phase or blast phase at any time, or
• •3. Intolerant of available TKIs
• •5. Performance score of at least 70% by Karnofsky or 0 to 1 by ECOG.
• •6. Adequate major non-hematopoietic organ system function as demonstrated by:
• •1. Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockcroft-Gault formula).
• •2. Bilirubin equal or less than 1.5 mg/dL except for Gilbert's disease. ALT or AST equal or less than 200 U/L for adults. Conjugated (direct) bilirubin less than 2x upper limit of normal.
• •3. Left ventricular ejection fraction equal or greater than 45%.
• •4. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 60% predicted corrected for hemoglobin.
• •7. Ability to understand and willingness to sign the written informed consent document.
• •8. 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.