The goal of this clinical research study is to find the recommended safe dose of TGFBR2 KO CAR27/IL-15 NK cells that can be given to patients with relapsed/refractory disease. The safety and effectiveness of this treatment will also be studied.
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.
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%.
Active grade III-V cardiac failure as defined by the New York Heart Association Criteria
Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment).
Active central nervous system leukemia
Known human immunodeficiency virus (HIV) seropositive, unless well-controlled on stable doses of anti-retroviral therapy.
Single group
Dexamethasone
DrugGiven Orally
Cyclophosphamide
DrugGiven by IV
Fludarabine
DrugGiven by IV
Decitabine
DrugGiven by IV
TGFBR2 KO CAR27/IL-15 NK cells
Biological/VaccineGiven by Infusion
Safety and Adverse Events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Response rates (AML cohort)
Rate of complete remission (CR) + CR with incomplete hematologic recovery (CRi) + CR with CR with partial hematologic recovery (CRh)
Response rates (MDS/CMML) cohort
Rate of CR + partial remission (PR) + CR with limited count recovery (CRL), CRh, hematologic improvement (HI) for MDS; rate of CR + PR + marrow CR (mCR) + clinical benefit (CB) for CMML
CR rate
Rate of CR in each cohort
Measurable residual disease (MRD) negativity (AML cohort)
Rate of MRD negativity assessed by flow cytometry
Duration of response
Time from response to relapse
Relapse-free survival
Time from response to relapse or death from any cause
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