Using BAFF CAR-T cells to treat non-Hodgkin lymphoma

LMY-920 for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

This study is testing a new type of treatment using specially modified immune cells to see if it can help people with non-Hodgkin lymphoma who haven't had success with other therapies.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Luminary Therapeutics (industry)
• Drugs / interventions: CAR-T, chemotherapy, radiation, chimeric antigen receptor
• Locations: 2 sites (Cleveland, Ohio and 1 other locations)
• Trial ID: NCT05312801 on ClinicalTrials.gov

What this trial studies

This phase 1 study evaluates the safety and initial effectiveness of BAFF CAR-T cells in patients with relapsed non-Hodgkin lymphoma who have not responded to previous treatments. The therapy involves genetically engineered T cells that target specific receptors on malignant B cells, aiming to improve outcomes for patients who have exhausted other treatment options. Participants will undergo a lymphodepletion regimen followed by the administration of BAFF CAR-T cells, with the goal of determining the recommended dose for future studies.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with histologically confirmed relapsed or refractory non-Hodgkin lymphoma after multiple lines of therapy.

Not a fit: Patients with central nervous system lymphoma or those who have not undergone sufficient prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with refractory non-Hodgkin lymphoma.

How similar studies have performed: While CAR-T cell therapies have shown promise, this specific approach using BAFF CAR-T cells is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion 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.

Exclusion Criteria:

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.

Where this trial is running

Cleveland, Ohio and 1 other locations

• University Hospitals Seidman Cancer Center — Cleveland, Ohio, United States (NOT_YET_RECRUITING)
• Taussig Cancer Institute | Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: Paolo F. Caimi, MD — Cleveland Clinic Taussig Cancer Institute
• Study coordinator: Paolo F. Caimi, MD

Conditions: Lymphoma, Non-Hodgkin Lymphoma, B-Cell, non-Hodgkin lymphoma.