Phase 1 Study of BAFF CAR-T Cells (LMY-920) for Non-Hodgkin Lymphoma

Eligibility Criteria

• 1. Subjects must have histologically confirmed non-Hodgkin lymphoma relapsed after 2 or more lines of therapy or disease refractory to chemotherapy (defined as progressive disease or stable disease lasting ≤6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence ≤12 months after prior autologous stem cell transplantation (ASCT).
• 2. No evidence of central nervous system (CNS) lymphoma.
• 3. Male or female \> 18 years of age.
• 4. Eastern Cooperative Oncology Group Performance status ≤ 2.
• 5. At least one measurable lesion.
• 6. \>2 weeks since prior radiation therapy or systemic therapy at the time of leukapheresis.
• 7. Total bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's syndrome).
• 8. Aspartate aminotransferase/alanine transferase ≤ 2.5 X institutional upper limit of normal.
• 9. Serum creatinine \< 1.5 mg/dL.
• 10. Cardiac ejection fraction of \>50%, and no evidence of pericardial effusion, as determined by an echocardiogram.
• 11. Adequate pulmonary function as defined as pulse oximetry ≥ 92% on room air.
• 12. Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document.
• 13. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for at least 90 days after the BAFF CAR-T cell infusion.
• 14. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
• 1. ASCT within 6 weeks of informed consent.
• 2. History of allogeneic hematopoietic stem cell transplantation.
• 3. Active graft-versus-host disease.
• 4. Active central nervous system or meningeal involvement by lymphoma or leukemia.
• 5. Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).
• 6. Less than 28 days elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection.
• 7. New York Heart Association class IV congestive heart failure.
• 8. Cardiovascular disorders including unstable angina pectoris, clinically significant cardiac arrhythmias, myocardial infarction or stroke (including transient ischemic attack, or other ischemic event) within 6 months prior to registration.
• 9. Active infection requiring intravenous systemic treatment.
• 10. HIV seropositivity.
• 11. Pregnant or breastfeeding women.
• 12. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
• 13. Serologic status reflecting active hepatitis B or C infection.
• 14. Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
• 15. Subjects with uncontrolled intercurrent illness.
• 16. Known additional malignancies which require systemic treatment.
• 17. History of autoimmune disease with requirement of immunosuppressive medications (other than low dose steroids) within 6 months.