Relapsed or Refractory Follicular LymphomaPhase 1NCT07343934
huCART19-IL18-eDHFR Cells in Relapsed/Refractory Follicular Lymphoma
A Phase 1 study testing huCART19-IL18-eDHFR cells and [18F]Fluoropropyl-Trimethoprim in people with Relapsed or Refractory Follicular Lymphoma, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Follicular Lymphoma
- What is being tested?
- huCART19-IL18-eDHFR cells and [18F]Fluoropropyl-Trimethoprim
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2026to Nov 2042
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 or lenalidomide.
- Must have progressed within 2 years after second or higher line of therapy.
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- 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
Who cannot join
- Active hepatitis B or hepatitis C infection
- Any active, uncontrolled infection.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification (See Appendix 5).
- 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.
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- Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.3.
- 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. For additional details regarding these restrictions, please see Section 5.3.
- 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.
- Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
- Known allergy to trimethoprim or Bactrim (TMP-SMX).
- 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 daily 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, as described in Protocol Section 4.3.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Abramson Cancer Center Clinical Trials Service contact
Stephen Schuster, MD contact
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Abramson Cancer Center Clinical Trials Service, 215-349-8245, PMCancerResearch@pennmedicine.upenn.edu
About this study
Official title: 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.
- Being tested
- huCART19-IL18-eDHFR cells, [18F]Fluoropropyl-Trimethoprim
- Keywords
- Follicular Lymphoma, CAR T cells
- Medical subject headings
- Recurrence, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
huCART19-IL18-eDHFR cellsBiological
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)
[18F]Fluoropropyl-TrimethoprimDrug
Also called [18F]FP-TMP
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).
| Study group | Role | What they receive |
|---|---|---|
| Arm A - DL1 | Experimental | IV administration of a single flat dose of 7x10[6] huCART19-IL18-eDHFR cells. [18F]FP-TMP PET/CT scan. Receives: 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. Receives: Biological: huCART19-IL18-eDHFR cells; Drug: [18F]Fluoropropyl-Trimethoprim |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 6 months after huCART19-IL18-eDHFR administration
Secondary outcomes (12)
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,
Measured: 3 Months
Incidence of adverse events as assessed by CTCAE v6.0
Type, frequency, severity, and attribution of adverse events
Measured: up to 15 years after huCART19-IL18-eDHFR administration
Occurrence of Treatment-Limiting Toxicities (TLTs)
Unacceptable toxicity as defined by the protocol
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 15 years after last huCART-IL18-eDHFR administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2026
- Study start18 May 2026
- Primary completionNov 2027 (estimated)
- Study completionNov 2042 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose Level -1 (DL-1) will only be explored if ≥ 2 Treatment Limited Toxicities occur at any time in DL1
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Follicular Lymphoma Foundation
- Responsible party
- Sponsor
- Investigators
- Stephen Schuster, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07343934
- Sponsor's protocol ID
- 25-2097 (859859; 30425)
- Status last verified
- Sep 2026
- First submitted
- 19 Dec 2025
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of huCART19-IL18-eDHFR Cells in Patients With Relapsed or Refractory Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT07343934
- Acronym / sponsor ID
- 25-2097 (859859; 30425)
- Keywords
- Follicular Lymphoma, CAR T cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Follicular Lymphoma Foundation
- Study start
- 18 May 2026 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2042 (estimated)
- First posted
- 15 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Dose Level -1 (DL-1) will only be explored if ≥ 2 Treatment Limited Toxicities occur at any time in DL1
| Arm | Type | Receives |
|---|---|---|
| Arm A - DL1 | Experimental | Biological: huCART19-IL18-eDHFR cells, Drug: [18F]Fluoropropyl-TrimethoprimIV administration of a single flat dose of 7x10[6] huCART19-IL18-eDHFR cells. [18F]FP-TMP PET/CT scan. |
| Arm A - DL-1 | Experimental | Biological: huCART19-IL18-eDHFR cells, Drug: [18F]Fluoropropyl-TrimethoprimIV administration of a single flat dose of 3x10[6] huCART19-IL18-eDHFR cells. [18F]FP-TMP PET/CT scan. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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.
Key exclusion criteria (15 listed)
- Active hepatitis B or hepatitis C infection
- Any active, uncontrolled infection.
- Class III/IV cardiovascular disability according to the New York Heart Association Classification (See Appendix 5).
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| huCART19-IL18-eDHFR cellsGenetically 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) | Biological | Arm A - DL-1, Arm A - DL1 |
| [18F]Fluoropropyl-TrimethoprimAlso: [18F]FP-TMPCo-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). | Drug | Arm A - DL-1, Arm A - DL1 |
Primary outcome
Change in Tumor Uptake on [18F]FP-TMP PET/CT
Time frame: Up to 6 months after huCART19-IL18-eDHFR administration
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.
12 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Abramson Cancer Center Clinical Trials Service contact
Stephen Schuster, MD contact
Stephen Schuster, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing huCART19-IL18-eDHFR cells and [18F]Fluoropropyl-Trimethoprim in people with Relapsed or Refractory Follicular Lymphoma, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Abramson Cancer Center Clinical Trials Service (215-349-8245, PMCancerResearch@Pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Tumor Uptake on [18F]FP-TMP PET/CT (time frame: Up to 6 months after huCART19-IL18-eDHFR administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.