Overview
A Phase 1 Study Evaluating BAFFR-targeting CAR T Cells for Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)
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
Inclusion Criteria:
- Informed Consent: Signed informed consent by the participant or legally authorized representative.
- Age \& Performance Status:
- Age ≥ 18 years
- ECOG performance status ≤ 2
- 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.
- Measurable Disease: Tumor ≥1.5 cm on CT/PET scan or evidence of disease in blood, BM, GI, skin, or spleen.
- Prior CAR T-cell Therapy: Allowed if ≥ 3 months since last treatment and CD19 CAR-T persistence \< 5% before leukapheresis.
- 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.
- Infectious Disease Screening: Seronegative for HIV, active HBV, active HCV (or undetectable viral load if positive).
- Reproductive Considerations:
- Negative pregnancy test for females of childbearing potential.
- Use of effective contraception or abstinence through 3 months post-treatment.
Exclusion Criteria:
- Prior Therapies \& Transplants:
- Prior allogeneic SCT.
- Autologous SCT \< 6 months before leukapheresis.
- Concurrent systemic steroids or chronic immunosuppressant use.
- Disease-Specific Exclusions:
- Cardiac lymphoma involvement.
- Need for urgent therapy due to tumor-related complications (e.g., bowel obstruction).
- 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.
- Pregnancy \& Breastfeeding: Females who are pregnant or nursing.
- Other Considerations:
- Investigator-determined safety concerns.
- Potential noncompliance with study procedures.
