baffr-targeting car t cells for patients with relapsed or refractory b-nhl

Conditions: Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Summary: 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.

Eligibility criteria:
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.

Keywords: relapsed or refractory mantle cell lymphoma baffr-car t cells b-cell non-hodgkin's lymphoma b-nhl baffr mcl lbcl