huCART19-IL18-eDHFR Cells in Relapsed/Refractory Follicular Lymphoma

Prior treatment

• Active acute or chronic GVHD requiring systemic therapy.
• Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.3.
• Receipt of prior huCART19 or huCART19-IL18 therapy.
• Active treatment with trimethoprim, methotrexate, or other antifolate chemotherapy, or anticipated use of these drugs during the active treatment phase of the study. For additional details regarding these restrictions, please see Section 5.3.
• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.

Other illness

• Active hepatitis B or hepatitis C infection
• Any active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification (See Appendix 5).
• Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Active CNS involvement. Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
• Known allergy to trimethoprim or Bactrim (TMP-SMX).
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Lab values

• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Other

• Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods, as described in Protocol Section 4.3.

• Signed informed consent form
• Male or females age ≥ 18 years
• Diagnosis of follicular lymphoma, grades 1-3A
• Relapsed or refractory disease after at least 2 prior lines of systemic therapy as follows:
  • Prior therapy must include an anti-CD20 monoclonal or bispecific antibody and an alkylating agent or lenalidomide.
  • Must have progressed within 2 years after second or higher line of therapy.
• Documentation of CD19 expression on malignant cells by flow cytometry/IHC from a CLIA certified laboratory. Results must be within 6 months of physician-investigator confirmation of eligibility and after any intervening CD19 directed therapy since expression confirmed.
• Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:
  • Have no active GVHD and require no immunosuppression
  • Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility
• Evidence of progressive disease within 12 weeks of physician-investigator confirmation of eligibility.
• ECOG Performance Status that is either 0 or 1.
• Adequate organ function defined as:
  • Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis.
  • ALT/AST ≤ 3 x ULN
  • Direct bilirubin ≤ 2.0 mg/dl; for patients with Gilbert's syndrome direct bilirubin must be ≤ 3.0 mg/dl
  • Left Ventricular Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
  • Must have minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air