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

Prior treatment

• 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
  • 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 \</=20%
• 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

Other illness

• Patients with active known autoimmune disease are ineligible
• 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 history or presence of clinically significant neurological disorders such as epilepsy, generalized seizure disorder, severe brain injuries are ineligible

Lab values

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

Age

• 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

Other

• Karnofsky performance status \<70
• Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study

• 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