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| Name | Class |
|---|---|
| Follicular Lymphoma Foundation | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A - DL1 | Experimental | IV administration of a single flat dose of 7x10[6] huCART19-IL18-eDHFR cells. [18F]FP-TMP PET/CT scan. |
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| Arm A - DL-1 | Experimental | IV administration of a single flat dose of 3x10[6] huCART19-IL18-eDHFR cells. [18F]FP-TMP PET/CT scan. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| huCART19-IL18-eDHFR cells | Biological | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 6 months after huCART19-IL18-eDHFR administration |
| Measure | Description | Time Frame |
|---|---|---|
| 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, | 3 Months |
| Incidence of adverse events as assessed by CTCAE v6.0 |
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Inclusion Criteria:
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:
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:
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:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Abramson Cancer Center Clinical Trials Service | Contact | 215-349-8245 | PMCancerResearch@Pennmedicine.upenn.edu | |
| Stephen Schuster, MD | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Stephen Schuster, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008228 | Lymphoma, Non-Hodgkin |
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Dose Level -1 (DL-1) will only be explored if ≥ 2 Treatment Limited Toxicities occur at any time in DL1
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|
| [18F]Fluoropropyl-Trimethoprim | Drug | 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). |
|
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Type, frequency, severity, and attribution of adverse events |
| up to 15 years after huCART19-IL18-eDHFR administration |
| Occurrence of Treatment-Limiting Toxicities (TLTs) | Unacceptable toxicity as defined by the protocol | 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 | 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. | 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 | 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. | 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 | 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 | 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 | 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 | 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 | Up to 15 years after last huCART-IL18-eDHFR administration |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |