CAR T cells with IL-18 and eDHFR for relapsed or refractory follicular lymphoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is an open-label, single-arm phase 1 trial evaluating huCART19-IL18-eDHFR CAR T cells in relapsed or refractory follicular lymphoma. The study uses a flat-dose of 7x10^6 cells without prior lymphodepletion in Treatment Arm A and may add additional arms in the future. A unique feature is the co-expression of eDHFR to enable PET/CT imaging of CAR T-cell trafficking using an investigational radiolabeled agent, 18F FP-TMP, to explore feasibility and potential correlation with response. Primary goals focus on feasibility and safety, with preliminary signals of efficacy. Enrollment requires confirmed CD19 expression and completion of at least two prior lines of systemic therapy with specific prior treatments, among other criteria.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Signed informed consent form
2. Male or females age ≥ 18 years
3. Diagnosis of follicular lymphoma, grades 1-3A
4. Relapsed or refractory disease after at least 2 prior lines of systemic therapy as follows:

   1. Prior therapy must include an anti-CD20 monoclonal or bispecific antibody and an alkylating agent or lenalidomide.
   2. Must have progressed within 2 years after second or higher line of therapy.
5. 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.
6. Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:

   1. Have no active GVHD and require no immunosuppression
   2. Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility
7. Evidence of progressive disease within 12 weeks of physician-investigator confirmation of eligibility.
8. ECOG Performance Status that is either 0 or 1.
9. Adequate organ function defined as:

   1. Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis.
   2. ALT/AST ≤ 3 x ULN
   3. Direct bilirubin ≤ 2.0 mg/dl; for patients with Gilbert's syndrome direct bilirubin must be ≤ 3.0 mg/dl
   4. Left Ventricular Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
   5. Must have minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air

Exclusion Criteria:

1. Active hepatitis B or hepatitis C infection
2. Any active, uncontrolled infection.
3. Class III/IV cardiovascular disability according to the New York Heart Association Classification (See Appendix 5).
4. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
5. Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
6. Active acute or chronic GVHD requiring systemic therapy.
7. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications, please see Section 5.3.
8. Receipt of prior huCART19 or huCART19-IL18 therapy.
9. 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.
10. 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.
11. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
12. Known allergy to trimethoprim or Bactrim (TMP-SMX).
13. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
14. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg daily of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
15. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods, as described in Protocol Section 4.3.

Where it's running

• University of Pennsylvania
  Philadelphia, Pennsylvania, United States Recruiting

Study contacts

• Principal investigator: Stephen Schuster, MD — University of Pennsylvania
• Study coordinator: Abramson Cancer Center Clinical Trials Service
• Email: PMCancerResearch@Pennmedicine.upenn.edu
• Phone: 215-349-8245

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Flurpiridaz F-18 PET/CT to Find Parathyroid Adenomas

  This study tests whether Flurpiridaz F-18 PET/CT can better detect abnormal parathyroid glands in adults with primary hyperparathyroidism before surgery.

  Recruiting Early Phase 1 University of Pennsylvania · Philadelphia, Pennsylvania · NCT07910097

• Low-intensity focused ultrasound targeting the subthalamic nucleus for OCD

  A short test is being done to see if a wearable, non-invasive ultrasound device can safely and tolerably help adults with OCD by targeting a brain region called the subthalamic nucleus.

  Recruiting Phase 2 University of Pennsylvania · Philadelphia, Pennsylvania · NCT07887633

• Safe firearm storage: preferred device choice vs. standard cable locks

  This study tests whether giving people a choice of storage devices for firearms leads to safer storage at home compared with just sending cable locks.

  Recruiting University of Pennsylvania · Philadelphia, Pennsylvania · NCT07886983

• Add-on anti-inflammatory therapy for adults with depression and high inflammation

  This study tests whether adalimumab, given with your regular antidepressant Lexapro, can improve depressive symptoms in adults with major depressive disorder and high inflammation.

  Recruiting Phase 2 University of Pennsylvania · Philadelphia, Pennsylvania · NCT07845604

• FAP PET/CT in adults with pulmonary TB

  This early-phase study tests whether a FAP PET/CT scan can map lung fibrosis in adults with pulmonary TB before starting treatment and after cure.

  Recruiting Early Phase 1 University of Pennsylvania · Philadelphia, Pennsylvania · NCT07830771

• Gender Inclusive Sexuality Talks for Parents and Teens

  This trial tests the GIST program to help parents talk with transgender, gender-diverse, lesbian, or bisexual female youth about sexuality at home.

  Recruiting University of Pennsylvania · Philadelphia, Pennsylvania · NCT07825571

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.