Phase 1 Study of huCART19-IL18-eDHFR Cells in Patients With Relapsed or Refractory Follicular Lymphoma
This is a phase 1, open-label study to evaluate the feasibility, safety and preliminary efficacy of huCART19-IL18-eDHFR cells administered in patients with relapsed or refractory follicular lymphoma. This study will be initiated as a single arm study (Treatment Arm A), which will evaluate the use of huCART19-IL18-eDHFR cells without prior lymphodepletion. In this Treatment Arm A, all subjects will receive a single flat dose of 7x10\[6\] huCART19-IL18-eDHFR cells (Dose Level 1; DL1). Additional treatment arms may also be introduced in the future, via subsequent amendment(s). Co-expression of eDHFR within huCART19-IL18 cells will allow the trafficking of the transduced CAR T cells to be visualized by PET/CT imaging using an investigational radiolabeled imaging agent \[18F\]Fluoropropyl-Trimethoprim (also known as \[18F\]FP-TMP). The feasibility of using \[18F\]FP-TMP PET/CT imaging to detect and measure the eDHFR-expressing CAR T cells will be investigated, as well as its ability to provide insight into CAR T cell pharmacokinetics, biodistribution, and persistence.
• 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.
⁃ 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