Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies

Objectives:

Primary objective:

To determine the safety and relative efficacy of Chimeric antigen receptors
(CAR).CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood natural killer (CB-NK) cells in
patients with relapsed/refractory CD19+ B lymphoid malignancies.

Secondary Objectives:

1. To assess the overall response rate (complete and partial response rates).

2. To quantify persistence of infused allogeneic donor CAR-transduced CB-derived NK cells
in the recipient.

3. To conduct comprehensive immune reconstitution studies.

Inclusion Criteria:

1. Patients with history of CD 19 positive B-lymphoid malignancies (ALL, CLL, NHL) who
have received at least 2 lines of standard chemoimmunotherapy or targeted therapy and
have persistent disease.

2. Patients with ALL, CLL, NHL with relapsed disease following standard therapy or a stem
cell transplant.

3. Patients at least 3 weeks from last cytotoxic chemotherapy at the time of starting
lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or
other targeted therapies until at least two weeks prior to administration of
lymphodepleting chemotherapy.

4. Karnofsky/Lansky Performance Scale > 70.

5. Adequate organ function: a. Renal: Creatinine clearance (as estimated by Cockcroft
Gault) >/= 60 cc/min. b. Hepatic: ALT/AST liver metastases, Total bilirubin Syndrome in whom total bilirubin must be fraction >/= 50%, no evidence of pericardial effusion as determined by an ECHO or
MUGA, and no clinically significant ECG findings. d. Pulmonary: No clinically
significant pleural effusion, baseline oxygen saturation > 92% on room air.

6. Able to provide written informed consent.

7. 7-80 years of age.

8. All participants who are able to have children must practice effective birth control
while on study. Acceptable forms of birth control for female patients include:
hormonal birth control, intrauterine device, diaphragm with spermicide, condom with
spermicide, or abstinence, for the length of the study. If the participant is a female
and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If
the participant becomes pregnant during this study, she will be taken off this study.
Men who are able to have children must use effective birth control while on the study.
If the male participant fathers a child or suspects that he has fathered a child while
on the study, he must immediately notify his doctor.

9. Signed consent to long-term follow-up protocol PA17-0483.

Exclusion Criteria:

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

2. Known positive serology for HIV.

3. Presence of Grade 3 or greater toxicity from the previous treatment.

4. Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials
for management. Note: Simple UTI and uncomplicated bacterial pharyngitis are permitted
if responding to active treatment.

5. Presence of active neurological disorder(s).

6. Concomitant use of other investigational agents.