Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T Cells) for the Treatment of Relapsed or Refractory CD19+ Hematologic Malignancies

Inclusion Criteria:

* Patients with relapsed refractory B Cell malignancies which commonly express CD-19.

  * Eligible disease subtypes include the following:

    * Patients with diffuse large B-cell lymphoma (de novo or diffuse large B-cell lymphoma \[DLBCL\] transformed from an indolent lymphoma (follicular lymphoma, chronic lymphocytic leukemia) or high grade B-cell Lymphoma (HGBL):

      * Relapsed or refractory DLBCL or high-grade B-cell lymphoma (HGBL) following 2 or more prior chemoimmunotherapy regimens containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and requiring further treatment.
      * Relapse following a single prior chemoimmunotherapy regimen containing an anthracycline and CD20-directed therapy following diagnosis of de novo DLBCL/HGBL or DLBCL arising from indolent lymphoma and considered ineligible for high dose chemotherapy and autologous stem cell rescue as determined by the investigator.
      * Patients must have at least one fludeoxyglucose F-18 (FDG)-avid (PET-avid) measurable lesion.
      * Biopsy confirmation of relapsed or refractory DLBCL is required.
    * Chronic lymphocytic leukemia after 2 lines of therapy including a BTKi (bruton tyrosine kinase inhibitor).
    * Mantle cell lymphoma after 2 lines of therapy. Patients must have previously received chemoimmunotherapy and a prior BTK inhibitor.
    * Follicular lymphoma after 2 lines of therapy.
* For cohort 1A specifically, patients must additionally have received a prior CD19-targeted CAR T-cell therapy or not have an indication for a Food and Drug Administration (FDA)-approved commercial CD19-targeted CAR T-cell therapy. This will include patients with relapsed/refractory DLBCL, FL, CLL and MCL.
* For cohorts other than cohort 1A (and if needed, cohort -1), patients with an indication for an FDA approved commercial CD19-targeted CAR T-cell therapy are eligible following an informed consent discussion that reviews the risks and benefits of the FDA-approved commercial CD19-targeted CAR T-cell therapy vs the investigational product.
* Prior CD19-targeted therapies, including CAR T-cell therapy, does not exclude participation; however, CD19 expression by immunohistochemical staining or flow cytometry must be confirmed prior to enrollment for patients who have received such therapies.
* Age ≥ 18 years of age.
* Creatinine Clearance \> 30 mL/min (Cockroft-Gault equation).
* Direct bilirubin ≤ 2.0 mg/dL (unless related to disease).
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (unless related to disease).
* Adequate pulmonary function as assessed by ≥ 90% oxygen saturation on room air by pulse oximetry.
* Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Patients of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.

Exclusion Criteria:

* Pregnant or lactating patients.
* Impaired cardiac function (left ventricular ejection fraction \[LVEF\] \< 40%) as assessed by ECHO or MUGA scan during screening.
* Patients with active graft versus host disease following allogeneic hematopoietic cell transplantation requiring systemic T cell suppressive therapy are ineligible.
* Patients with active autoimmune disease requiring systemic T cell suppressive therapy are ineligible.
* Patients with following cardiac conditions will be excluded:

  * New York Heart Association (NYHA) stage III or IV congestive heart failure.
  * Myocardial infarction ≤ 6 months prior to enrollment.
  * Any history of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
* Patients with HIV are ineligible.
* Patients with active hepatitis B infection (as manifest by either detectable hepatitis B virus deoxyribonucleic acid \[DNA\] by polymerase chain reaction \[PCR\] and/or positivity for hepatitis B surface antigen) are ineligible.
* Patients with active hepatitis C infection (as manifest by detectable hepatitis C virus ribonucleic acid \[RNA\] by PCR) are ineligible. Patients with detectable antibodies to hepatitis C virus will be screened by PCR for evidence of active infection.
* 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.
* Patients with primary central nervous system (CNS) disease are ineligible.
* Unwilling or unable to follow protocol requirements.
* Any other condition/issue which, in the opinion of the treating physician, would make the patient ineligible for the study.