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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
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)
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).
University of Pennsylvania
Philadelphia, Pennsylvania, United States
RECRUITINGChange 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
Evaluate manufacturing feasibility
The proportion of subjects with huCART19-IL18-eDHFR products that fail to meet the product release criteria, out of the number of eligible subjects in whom manufacturing was attempted,
Time frame: 3 Months
Incidence of adverse events as assessed by CTCAE v6.0
Type, frequency, severity, and attribution of adverse events
Time frame: up to 15 years after huCART19-IL18-eDHFR administration
Occurrence of Treatment-Limiting Toxicities (TLTs)
Unacceptable toxicity as defined by the protocol
Time frame: 28 days after huCART19-IL18-eDHFR administration
Overall Response/Remission Rate (ORR)
Proportion of subjects with CR or PR at Month 3 as compared to baseline
Time frame: Month 3
Best Overall Response (BOR)
Proportion of subjects with a best overall disease response of CR or PR recorded between the protocol-required Month 3 disease assessment timepoint and the end of primary follow-up (Month 12); or start of new anticancer therapy (including huCART19-IL18-eDHFR retreatment), whichever comes first.
Time frame: From Month 3 up to Month 12
Duration of Response (DOR)
Time from the date when the response criteria of CR or PR is first met (at or following Month 3), to the date of confirmed disease progression, death, or other censoring event
Time frame: From Month 3 up to 15 years
Progression-Free Survival (PFS)
Duration of time from huCART19-IL18-eDHFR cell infusion (Day 0) to the date of confirmed disease progression or death.
Time frame: Up to 15 years
Overall survival (OS)
Duration of time from the first huCART19-IL18-eDHFR infusion (Day 0) to the date of death, for any reason
Time frame: Up to 15 years after last huCART-IL18-eDHFR administration
Retreatment - Overall Response/Remission Rate (ORR)
Proportion of subjects with CR or PR at Month 3-R as compared to retreatment baseline
Time frame: Up to Month 3-Retreatment
Retreatment - Best Overall Response (BOR)
Proportion of subjects with a best overall disease response of CR or PR recorded between the protocol-required Month 3-R disease assessment timepoint and the end of primary retreatment follow-up (Month 12-R); or start of new anticancer therapy, whichever comes first
Time frame: From Month 3-Retreatment up to Month 12-Retreatment
Retreatment - Duration of Response (DOR)
Time from the date when the response criteria of CR or PR is first met (at or following Month 3-R), to the date of confirmed disease progression, death, or other censoring event
Time frame: From Month 3-Retreatment up to 15 years after last huCART-IL18-eDHFR administration
Retreatment - Progression-Free Survival (PFS)
Duration of time from huCART19-IL18-eDHFR retreatment infusion (Day 0-R) to the date of confirmed disease progression or death
Time frame: Up to 15 years after last huCART-IL18-eDHFR administration
Abramson Cancer Center Clinical Trials Service
CONTACT
Stephen Schuster, MD
CONTACT
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