A Trial of "Armored" CAR T Cells Targeting CD19 For Patients With Relapsed CD19+ Hematologic Malignancies

Inclusion Criteria:

- Patients must have CD19+ B cell malignancy with relapsed or refractory disease,
defined as below:

Patients with CLL:

- Refractory to or relapsed after at least 2 prior chemo or chemoimmunotherapy (e.g.
FCR, BR) requiring further treatment

- Refactory to or relapsed after at least 1 prior biologic agent (e.g. Ibrutinib,
idelalisib, venetoclax, except a single agent anti-CD20 monoclonal antibody) requiring
further treatment

Patients with iNHL (FZ, MZL, WM):

- Refractory or relapsed after at least 2 lines of chemoimmunotherapy (including at
least one course of anti-CD20 antibody)

- Refractory or relapsed after at least 1 prior biologic agent (e.g. lenalidomide,
ibrutinib, idelalisib)

- Patients must have measurable disease (for WM patients, measureable disease is
demonstrable monoclonal paraprotein and bone marrow involvement)

Patients with DLBCL, Transformed B cell lymphoma, or High grade B cell lymphoma:

- Refractory to or relapsed after 1 or more prior chemoimmunotherapies with at least one
containing an anthracycline and CD20 directed therapy

- Transplant ineligible

- Biopsy proven relapsed disease

Patients with ALL, CML in lymphoid blast crisis or Burkitt's lymphoma:

- Refractory to at least 1 prior induction chemotherapy

- Relapsed after at least 1 prior multiagent systemic chemotherapy that included
induction and consolidation

- Patients with Philadelphia chromosome-positive ALL must have failed a second
generation tyrosine kinase inhibitor

- Age ≥ 18 years of age

- Creatinine ≤2.0 mg/100 ml, direct bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x
upper limit of normal (ULN)

- Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by
pulse oximetry

Exclusion Criteria:

- Karnofsky performance status <70

- Pregnant or lactating women. Women and men of childbearing age should use effective
contraception while on this study and continue for 1 year after all treatment is
finished

- Impaired cardiac function (LVEF <40%) as assessed by ECHO or MUGA scan

- Patients with active known autoimmune disease are ineligible

- Patients with following cardiac conditions will be excluded:

- New York Heart Association (NYHA) stage III or IV congestive heart failure

- Myocardial infarction
- History of clinically significant ventricular arrhythmia or unexplained syncope,
not believed to be vasovagal in nature or due to dehydration <6 months prior to
enrollment

- History of severe non-ischemic cardiomyopathy with EF
- Patients with HIV or active hepatitis B or hepatitis C infection are ineligible

- Patients with uncontrolled systemic fungal, bacterial, viral or other infection are
ineligible

- Patients with any concurrent active malignancies as defined by malignancies requiring
any therapy other than expectant observation or hormonal therapy, with the exception
of squamous and basal cell carcinoma of skin

- Patients with history or presence of clinically significant neurological disorders
such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible

- Any other issue which, in the opinion of the treating physician, would make the
patient ineligible for the study