19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers
19(T2)28z1xx Chimeric Antigen Receptor (CAR) T Cells in People With B-Cell Cancers
The purpose of this study is to test the safety of 19(T2)28z1xx CAR T cells in people with
 relapsed/refractory B-cell cancers. The researchers will try to find the highest dose of
 19(T2)28z1xx CAR T cells that causes few or mild side effects in participants. Once they find
 this dose, they can test it in future participants to see if it is effective in treating
 their relapsed/refractory B-cell cell cancers. This study will also look at whether
 19(T2)28z1xx CAR T cells work against participants' cancer.
Inclusion Criteria:

 -  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.

 Dose Escalation Phase:

 -  Histologically confirmed DLBCL and large B cell lymphoma, including

 -  DLBCL, not otherwise specified (NOS), or

 -  Transformed DLBCL from follicular lymphoma, or

 -  High-grade B cell lymphoma (excluding Burkitt's lymphoma), or

 -  Primary mediastinal large B cell lymphoma AND

 -  Chemotherapy refractory disease, defined as a failure to achieve at least a
 partial response or disease progression within 6 months to the last therapy, OR

 -  Disease progression or recurrence in ≤12 months of prior autologous stem cell
 transplant (ASCT), OR

 -  Relapsed disease after 2 or more prior chemoimmunotherapies with at least one
 containing an anthracycline and CD20 directed therapy

 -  Patients need to have radiographically documented disease

 Dose Expansion phase:

 Cohort 1: same disease subtypes as in the Dose Escalation Phase

 Cohort 2 (exploratory cohort) will include the following additional disease histology:

 -  Patients with CLL

 -  Refractory to or relapsed after at least 1 prior chemo or chemoimmunotherapies
 (e.g., FCR, BR) and 1 prior biologic agent (e.g. BTK, PI3K inhibitors,
 venetoclax) requiring further treatment, OR

 -  Refractory to or relapsed after at least 2 prior biologic agents (e.g. Ibrutinib,
 idelalisib, venetoclax, except a single agent anti-CD20 monoclonal antibody)
 requiring further treatment

 -  Patients with iNHL (FL, MZL, WM):

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

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

 -  Patients with Burkitt's lymphoma or transformed CLL to large cell lymphoma (i.e.
 Richter's transformation):

 -  Refractory to or relapsed after at least 1 prior multiagent systemic chemo or
 chemoimmunotherapy

 Exclusion Criteria:

 -  ECOG performance status ≥2.

 -  Patients with active CNS disease

 -  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 the 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

 -  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

 -  Patients with HIV or active hepatitis B or hepatitis C infection are ineligible.

 -  Patients with prior allogeneic hematopoietic stem cell transplant are eligible, if
 more than 3 months from transplant and if patients have no active graft versus host
 disease (GvHD) and not on systemic immunosuppressive therapy.

 -  Prior CD19-directed therapy including CD19 CAR T cells is allowed, as long as
 expression of CD19 is confirmed by flow cytometry or immunohistochemistry.

 -  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 the skin.

 -  Patients with 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.