A Phase I/II Study of CAR.70-Engineered IL15-Transduced Cord Blood-Derived NK Cells With TGF-beta Receptor 2 (TGFBR2) Knock Out in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapsed/Refractory Myeloid Malignancies

1. Diagnosis: Age 18-80 years with diagnosis of:

1. Relapsed or refractory AML or "treated secondary AML"

* Patients with a mutation that is targetable with an FDA-approved targeted therapy should have received at least one on these agents. . "Treated secondary AML "includes patients with prior diagnosis of a myeloid neoplasm (e.g. MDS) who received hypomethylating agents for this disease and subsequently progressed to AML. These patients must have received all of the following: a hypomethylating agent + venetoclax and intensive chemotherapy (if a suitable candidate for intensive therapy). These patients may be enrolled at the time of AML diagnosis if they have already received all of the treatments above for their antecedent myeloid neoplasm.

2. MDS that is intermediate, high-risk or very-high risk by the Revised International Prognostic Scoring System (R-IPSS)

* Bone marrow blasts must be \>5%.

* The disease must have either 1.) not have responded to at least 4 cycles of a hypomethylating agent or 2.) progressed or relapsed, regardless of the number of cycles received

3. CMML-1 or CMML-2

* Bone marrow blasts must be \>5%.

* The disease must have either 1.) not have responded to at least 4 cycles of a hypomethylating agent or 2.) progressed or relapsed, regardless of the number of cycles received

2. CD70 expression \>10% measured by immunohistochemistry or multiparameter flow cytometry

3. Performance status \</=2 (ECOG Scale)

4. Adequate liver, cardiac, renal and pulmonary function as defined by the following criteria:

1. Total serum bilirubin \</=2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the PI

2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \</=3 x ULN, unless due to the underlying leukemia approved by the PI

3. Serum creatinine \</=2x ULN or creatinine clearance \>/=30 mL/min

4. Left ventricular ejection fraction \>/=40% by echocardiogram or MUGA

5. Oxygen saturation \>/=93% on room air

5. Ability to understand and the willingness to sign a written informed consent document

6. Willingness to sign informed consent to long-term follow-up on protocol PA17-0483 to fulfill institutional responsibilities to regulatory agencies

7. Willingness to use adequate contraception prior to study entry, for the duration of study participation, and for 3 months after completion of study participation. For women of childbearing potential, adequate methods of contraception include: complete abstinence,, hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal Ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide.

What this study is about