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.
