Phase 1 Study of huCART19-IL18-eDHFR Cells in Patients With Relapsed or Refractory Follicular Lymphoma
Summary
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.
Arms & interventions
- BiologicalhuCART19-IL18-eDHFR cells
Genetically modified autologous T cells engineered by co-transduction with two lentiviral vectors; one vector expressing a chimeric antigen receptor (CAR) targeting the CD19 antigen and human Interleukin 18 (IL-18), and a second vector expressing E.coli dihydrofolate reductase (eDHFR)
- Drug[18F]Fluoropropyl-Trimethoprim
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).
Outcome measures
Primary
Change in Tumor Uptake on [18F]FP-TMP PET/CT
In order to evaluate the feasibility of using \[18F\]FP-TMP PET/CT imaging to detect and measure eDHFR-expressing CAR-T cells, the change in tumor uptake on the post-infusion \[18F\]FP-TMP PET/CT scans will be compared to baseline.
Time frame: Up to 6 months after huCART19-IL18-eDHFR administration
Secondary
Evaluate manufacturing feasibility
Time frame: 3 Months
Incidence of adverse events as assessed by CTCAE v6.0
Time frame: up to 15 years after huCART19-IL18-eDHFR administration
Occurrence of Treatment-Limiting Toxicities (TLTs)
Time frame: 28 days after huCART19-IL18-eDHFR administration
Overall Response/Remission Rate (ORR)
Time frame: Month 3
Best Overall Response (BOR)
Time frame: From Month 3 up to Month 12
Duration of Response (DOR)
Time frame: From Month 3 up to 15 years
Progression-Free Survival (PFS)
Time frame: Up to 15 years
Overall survival (OS)
Time frame: Up to 15 years after last huCART-IL18-eDHFR administration
Retreatment - Overall Response/Remission Rate (ORR)
Time frame: Up to Month 3-Retreatment
Retreatment - Best Overall Response (BOR)
Time frame: From Month 3-Retreatment up to Month 12-Retreatment
Retreatment - Duration of Response (DOR)
Time frame: From Month 3-Retreatment up to 15 years after last huCART-IL18-eDHFR administration
Retreatment - Progression-Free Survival (PFS)
Time frame: Up to 15 years after last huCART-IL18-eDHFR administration
Eligibility criteria
Study locations (1)
University of Pennsylvania
Philadelphia, Pennsylvania, 19104