Phase I/II Study of CAR.70- Engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Hematological Malignances

Inclusion criteria:

1. Patients with hematological malignances with an expression of CD70 in thepre-enrollment tumor sample ≥ 10% measured by immunohistochemistry or flowcytometry.

2. Patients must meet diseases specific eligibility criteria (see below)

3. Patients at least 1 week from last cytotoxic chemotherapy at the time of startinglymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheralblood count control in AML, CML, and MDS patients until the day prior toadministration of lymphodepleting chemotherapy. Patients may continue tyrosinekinase inhibitors or other targeted therapies until up to three days prior toadministration of lymphodepleting chemotherapy.

4. Localized radiotherapy to one or more disease sites is allowed prior the infusionprovided that there are additional disease sites that are not irradiated to assessresponse

5. Karnofsky Performance Scale > 50% for patients who are >16 years old or Lansky score ≥50% for patients who are ≤16 years of age.

6. Adequate organ function:

7. Renal: Serum creatinine </= 2x ULN or estimated Glomerular Filtration Rate >/= 30 ml/min/1.73 m2

8. Hepatic: ALT/AST </= 3 x ULN or </= 5 x ULN if documented liver metastases,Total bilirubin </2xULN, except in subjects with Gilbert's Syndrome in whomtotal bilirubin must be </= 3 x.ULN. No history of liver cirrhosis. No ascites.

9. Cardiac: Cardiac ejection fraction >/= 40%, no clinically significantpericardial effusion as determined by an ECHO, and no uncontrolled arrhythmiasor symptomatic cardiac disease.

10. Pulmonary: No clinically significant pleural effusion (per PI discretion),baseline oxygen saturation > 92% on room air and adequate pulmonary functionwith FEV1, FVC and DLCO (corrected for Hgb) >50%.

11. Able to provide written informed consent.

12. 12-80 years of age.

13. Weight ≥40 kg

14. All participants who are able to have children must practice effective birth controlwhile on study and up to 3 months post completion of study therapy. Acceptable formsof birth control for female patients include: hormonal birth control, intrauterinedevice, diaphragm with spermicide, condom with spermicide, or abstinence, for thelength of the study. If the participant is a female and becomes pregnant or suspectspregnancy, she must immediately notify her doctor. If the participant becomespregnant during this study, she will be taken off this study. Men who are able tohave children must use effective birth control while on the study. If the maleparticipant fathers a child or suspects that he has fathered a child while on thestudy, he must immediately notify his doctor.

15. Signed consent to long-term follow-up protocol PA17-0483 to fulfill theinstitutional responsibilities to various regulatory agencies.

16. Are willing and able to provide informed consent, as appropriate (either directly orthrough a legally authorized representative [LAR])

Exclusion criteria:

1. Positive beta HCG in female of child-bearing potential defined as not postmenopausalfor 24 months or no previous surgical sterilization or lactating females.

2. Presence of clinically significant Grade 3 or greater toxicity from the previoustreatment, as determined by PI.

3. Presence of uncontrolled fungal, bacterial, viral, or other infection not respondingto appropriate therapy.

4. HIV with detectable viral load

5. Presence of active neurological disorder(s).

6. Active autoimmune disease within 12 months of enrollment

7. Amyloidosis or POEMS syndrome

8. Active cerebral or meningeal involvement by the malignancy

9. Active (defined as requiring therapy) acute or chronic GVHD

10. Any other malignancy known to be active, except for treated cervicalintra-epithelial neoplasia and non-melanoma skin cancer.

11. Presence of any other serious medical condition that may endanger the patient atinvestigator discretion.

12. Major surgery <4 weeks prior to first dose of the preparatory chemotherapy

13. Allogeneic SCT or DLI <12 weeks prior to first dose of preparatory chemotherapy

14. Concomitant use of other investigational agents.

15. Concomitant use of other anti-cancer agents.

16. Patients receiving systemic steroid therapy at time of NK cell infusion (physiological substitutive doses are allowed), or have received antithymocyteglobulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumabwithin 28 days of enrollment.

17. Patients receiving immunosuppressive therapy