A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

This phase I trial evaluates the side effects and best dose of BAFFR-CAR T cells in treating patients with B-cell Non-Hodgkin's Lymphoma (B-NHL) that has come back (recurrent) or does not respond to treatment (refractory). T cells are infection fighting blood cells that can kill cancer cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize BAFFR, a protein on the surface of cancer cells. These BAFFR-specific T cells may help the body's immune system identify and kill BAFFR+ cancer cells.

Inclusion Criteria:

1. Informed Consent: Signed informed consent by the participant or legally authorized representative.

2. Age & Performance Status:

   • Age ≥ 18 years
   • ECOG performance status ≤ 2

3. Diagnosis & Disease Criteria:

   • Histologically confirmed B-NHL, including LBCL, MCL, and FL/MZL subtypes meeting specified prior treatment conditions.
   • BAFF-R expression on lymphoma cells required.

4. Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.

5. Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence < 5% before leukapheresis.

6. Organ Function & Laboratory Criteria:

   • Hematologic: ANC ≥ 1000/μL, Platelets ≥ 75,000/μL (exceptions for BM involvement).
   • Liver Function: Bilirubin ≤ 1.5x ULN (except Gilbert's), AST/ALT < 3x ULN.
   • Renal Function: CrCl ≥ 50 mL/min.
   • Cardiac & Pulmonary: LVEF ≥ 45%, QTcF ≤ 480 ms, O₂ saturation > 91% on room air.

7. Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).

8. Reproductive Considerations:

   • Negative pregnancy test for females of childbearing potential.
   • Use of effective contraception or abstinence through 3 months post-treatment.

Exclusion Criteria:

1. Prior Therapies & Transplants:

   • Prior allogeneic SCT.
   • Autologous SCT < 6 months before leukapheresis.
   • Concurrent systemic steroids or chronic immunosuppressant use.

2. Disease-Specific Exclusions:

   • Cardiac lymphoma involvement.
   • Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).

3. Medical Conditions:

   • Active autoimmune disease requiring immunosuppressants.
   • Primary immunodeficiency.
   • Cardiac conditions, including NYHA Class III/IV heart disease, arrhythmia, recent MI (≤ 6 months), stroke (≤ 6 months), or significant VTE (≤ 6 months).
   • Neurologic conditions, including prior optic neuritis, CNS inflammatory diseases, or seizure disorders.
   • History of malignancy, unless resected/treated with curative intent or in remission for ≥ 3 years.
   • Uncontrolled systemic infections or active CNS lymphoma.

4. Pregnancy & Breastfeeding: Females who are pregnant or nursing.

5. Other Considerations:

   • Investigator-determined safety concerns.
   • Potential noncompliance with study procedures.