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

NCT07343934 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 859859 (30425)
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Relapsed or Refractory Follicular Lymphoma

Keywords

Follicular Lymphoma; CAR T cells

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• Evaluate manufacturing feasibility

  3 Months

• Incidence of adverse events as assessed by CTCAE v6.0

  up to 15 years after huCART19-IL18-eDHFR administration

• Occurrence of Treatment-Limiting Toxicities (TLTs)

  28 days after huCART19-IL18-eDHFR administration

• Overall Response/Remission Rate (ORR)

  Month 3

• Best Overall Response (BOR)

  From Month 3 up to Month 12

Study Arms (2)

Arm A - DL1

EXPERIMENTAL

IV administration of a single flat dose of 7x10\[6\] huCART19-IL18-eDHFR cells. \[18F\]FP-TMP PET/CT scan.

Biological: huCART19-IL18-eDHFR cells; Drug: [18F]Fluoropropyl-Trimethoprim

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.

Biological: huCART19-IL18-eDHFR cells; Drug: [18F]Fluoropropyl-Trimethoprim

Interventions

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)

Arm A - DL-1; Arm A - DL1

[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).

Also known as: [18F]FP-TMP

Arm A - DL-1; Arm A - DL1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Active hepatitis B or hepatitis C infection
• Any active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
• Active acute or chronic GVHD requiring systemic therapy.
• Dependence on systemic steroids or immunosuppressant medications.
• 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.
• 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.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Follicular Lymphoma Foundation: collaborator

MeSH Terms

Conditions

Recurrence; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Stephen Schuster, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245; PMCancerResearch@Pennmedicine.upenn.edu

Stephen Schuster, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose Level -1 (DL-1) will only be explored if ≥ 2 Treatment Limited Toxicities occur at any time in DL1

Study Record Dates

• First Submitted: December 19, 2025
• First Posted: January 15, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2042
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share