CD19+ Specific Chimeric Antigen Receptor T Cells in Treating Participants With CD19+ Lymphoid Malignancies

PRIMARY OBJECTIVES:

I. To determine the safety and maximum tolerated dose (MTD) of genetically modified,
CD19-specific T cells expressing membrane-bound form of IL-15 (mbIL15) and HER1t manufactured
under point of care (P-O-C) process (P-O-C CD19-mbIL15-chimeric antigen receptor [CAR]-T
cells) administered into patients with CD19+ advanced lymphoid malignancies.

SECONDARY OBJECTIVES:

I. To describe the feasibility of the P-O-C process. II. To determine the incidence and
grading of cytokine release syndrome (CRS) and neurotoxicity.

III. To determine persistence of genetically modified T cells. IV. To determine if cetuximab
can control numbers of infused T cells. V. To screen for the development of host immune
responses against the transgenes (one or more of CAR, mbIL15, HER1t).

VI. To determine cytokine profile of the patient with infused T cells. VII. To describe the
homing ability of the infused T cells. VIII. To assess disease response at day 30 and day
100. IX. To assess disease progression-free and overall survival. X. Emergence of CD19
negative (neg) malignant B cells.

OUTLINE: This is a dose-escalation study of CD19+ specific chimeric antigen receptor T cells.

CHEMOTHERAPY: Participants receive fludarabine intravenously (IV) over 1 hour and
cyclophosphamide IV over 3 hours on days -5, -4, and -3 in the absence of disease progression
or unacceptable toxicity.

T CELL INFUSION: Participants receive CD19+ specific chimeric antigen receptor T cells IV
over 15-30 minutes on day 0 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed for up to 15 years.

Inclusion Criteria:

- Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic
leukemia (ALL), non-Hodgkin lymphoma (NHL), small lymphocytic lymphoma (SLL), or
chronic lymphocytic leukemia (CLL) with active disease defined by presence of > 5%
malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual
disease by flow cytometry or molecular analysis for fusion proteins, and/or positive
imaging for extramedullary disease. Patients must have measurable disease at time of
study treatment.

- Confirmed history of CD19-positivity by flow cytometry for malignant cells.

- Karnofsky performance scale > 70.

- Patient able to provide written informed consent.

- Patient able to provide written informed consent for the long-term follow-up (LTFU)
gene therapy study.

- Absolute T-cell count (ATC) at screening >= 0.07 K/microL. This is defined as CD3+
T-cell percent (expressed as fraction of 100%) multiplied by the absolute lymphocyte
count (ALC, expressed in K/microL).

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

- Creatinine clearance (as estimated by Cockcroft Gault) >= 50 cc/min.

- Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 2.5 x upper limit
of normal (ULN) or =< 5 x ULN if documented liver metastases.

- Total bilirubin =< 1.5 mg/dL, except in subjects with Gilbert's syndrome in whom total
bilirubin must be =< 3.0 mg/dL.

- Cardiac ejection fraction >= 40%, and no clinically significant electrocardiogram
(ECG) findings.

- No clinically significant pleural effusion, baseline oxygen saturation > 92% on room
air.

- Negative human anti-mouse antibody (HAMA) result.

Exclusion Criteria:

- Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential
defined as not post-menopausal for 12 months or no previous surgical sterilization or
lactating females.

- Patients with known allergy to bovine or murine products.

- Positive serology for human immunodeficiency virus (HIV).

- Active hepatitis B or active hepatitis C.

- Has received a T-cell product within 6 weeks prior to planned infusion of genetically
modified T cells.

- Has received allogeneic hematopoietic cell transplantation (HSCT) within 3 months of
planned infusion of genetically modified T cells; HSCT >= 3 months from CAR-T cell
infusion eligible.

- History of allergic reactions to cetuximab.

- Active clinically significant infection within 7-days of study treatment.