Detailed Description
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.
Eligibility Criteria
Age Range: 18 years to No maximum
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.