Natural Killer Cell (CYNK-001) Infusions in Adults With AML
Natural Killer Cell (CYNK-001) Infusions in Adults With AML
This study will find the maximum tolerated dose or the maximum planned dose of CYNK-001 which
 contains natural killer (NK) cells derived from human placental CD34+ cells and
 culture-expanded. CYNK-001 cells will be given after lymphodepleting chemotherapy. The safety
 of this treatment will be evaluated, and researchers want to learn if NK cells will help in
 treating acute myeloid leukemia.
Treatment Eligibility Screening Patient Inclusion Criteria

 Patients must satisfy the following criteria to be enrolled in the study:

 -  Patient has eligible disease status: Primary or Secondary acute myeloid leukemia (AML)
 Patients in first of second Morphological Complete Remission (CR), Morphological
 Complete Remission with incomplete hematologic recovery (CRi), or Morphologic
 Leukemia-free State (MLFS) as defined by the European LeukemiaNet (ELN)
 recommendations for AML Response Criteria (Dohner, 2017).

 -  Patient with prior central nervous system involvement by malignancy are eligible
 provided that it has been treated and cerebral spinal fluid is clear for at least 2
 weeks prior to start of Lymphodepletion Regimen.

 -  Patient is minimal residual disease (MRD) positive, as assessed on bone marrow
 aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility
 assessment.

 o For the purposes of this study, MRD positivity is defined as greater than or equal
 to 0.1% blasts detected by MFC on BMA by the Sponsor-selected Central MRD analysis
 laboratory, where assay sensitivity allows for a Lower Limit of Detection (LOD) of 1 x
 10-4 (0.01%) or lower.

 -  Patient is ≥ 18 and ≤ 80 years of age at the time of signing the Study informed
 consent form (ICF).

 -  Patient understands and voluntarily signs the Study ICF prior to any study-related
 assessments/procedures are conducted.

 -  Patient is willing and able to adhere to the study schedule and other protocol
 requirements.

 -  Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2.

 -  Ability to be off immunosuppressive drugs for at least 3 days prior to the CYNK-001
 infusion. Steroids at the equivalent of no more than 7.5 mg prednisone per day are
 permissible.

 -  Female of childbearing potential (FCBP)* must not be pregnant and agree to not
 becoming pregnant for at least 28 days following the CYNK-001. FCBP must agree to use
 an adequate method of contraception during the treatment period.

 -  FCBP is a female who: 1) has achieved menarche at some point, 2) has not
 undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally
 postmenopausal (amenorrhea following cancer therapy does not rule out
 childbearing potential) for at least 24 consecutive months (i.e., has had menses
 at any time in the preceding 24 consecutive months).

 -  Male Patients must agree to use a condom during sexual contact for at least 28 days
 following the last infusion of CYNK-001, even if he has undergone a successful
 vasectomy.

 Treatment Eligibility Screening Patient Exclusion Criteria

 The presence of any of the following will exclude the Patient from enrollment:

 -  Patient has any significant medical condition, laboratory abnormality, or psychiatric
 illness that would prevent the Patient from participating in the study.

 -  Patient has any condition including the presence of laboratory abnormalities which
 places the Patient at unacceptable risk if he or she were to participate in the study.

 -  Patient has any condition that confounds the ability to interpret data from the study.

 -  Patient has bi-phenotypic acute leukemia.

 -  Patient has acute promyelocytic leukemia (APL).

 -  Patient has inadequate organ function as defined below at time of Treatment
 Eligibility Period:

 1. Patient has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or
 alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN).

 2. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as calculated
 using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or
 history of an abnormal eGFR < 60 and a decline of > 15 mL/min/1.73 m2 below
 normal in the past year.

 3. Patient has a bilirubin level > 2 mg/dL (unless Patient has known Gilbert's
 disease).

 -  Patient has had prior treatment with biologic antineoplastic agents less than 7 days
 before first CYNK-001 infusion and at least 5 half-lives. (Exception will be granted
 for monoclonal antibodies that are known to have long half-lives, in which case a
 minimum of 2 weeks from last dose will be required). For agents that have known AEs
 occurring beyond these specified days after administration, this period must be
 extended beyond the time during which acute AEs are known to occur. Treating
 physicians are encouraged to discuss cases with the Medical Monitor.

 -  Patient is pregnant or breastfeeding.

 -  Patient has new or progressive pulmonary infiltrates or pleural effusion large enough
 to be detected by chest x-ray or CT scan within 2 weeks of first CYNK-001 infusion.

 -  Patient has active autoimmune disease other than controlled connective tissue disorder
 or those who are not on active therapy.

 -  Patient has had a Bone Marrow transplant as part of their anti-AML treatment prior to
 first CYNK-001 infusion or plans to have transplant within the 28 day period following
 first CYNK-001 infusion. Exception includes relapsed patients who received prior Bone
 Marrow transplant as part of their treatment plan at initial diagnosis.

 -  Patient has a history of malignancy other than AML or other underlying hematologic
 conditions such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms
 (MPN) unless the Patient has been free of disease for greater than 3 years prior to
 CYNK 001 infusion. Exceptions will include the following malignancies:

 1. Basal cell carcinoma of the skin

 2. Squamous cell carcinoma of the skin

 3. Carcinoma in situ of the cervix

 4. Carcinoma in situ of the breast

 5. Incidental biological finding of prostate cancer (TNM stage of T1a or T1b)

 -  Patient has a history of severe asthma and is presently on chronic medications or has
 a history of other symptomatic pulmonary disease.

 -  Patient has uncontrolled graft versus host disease (GVHD) or GVHD requiring treatment
 with corticosteroids.

 -  Patient has an untreated chronic infection or has received treatment of any infection
 with systemic antibiotics within 2 weeks prior to first CYNK-001 infusion.
 Prophylactic antibiotic, antiviral, and antifungal medication are permissible.

 -  Patient has any other organ dysfunction (CTCAE Version 5.0 Grade 3 or greater) that
 will interfere with the administration of the therapy according to this protocol.

 -  Patient has a resting left ventricular ejection fraction (LVEF) of < 45% obtained by
 echocardiography or multi-gated acquisition scan (MUGA).

 -  Patient was treated with an investigational product within 28 days of first CYNK-001
 infusion. Patient must no longer be a participant in the previous interventional study
 at the time of CYNK-001 infusion. (Patients who are under survival follow-up or
 observation associated with a study are permitted, and if treatment information is
 collected for this period, "Investigational Study" must be used to capture the study
 treatment.).