BAFF CAR-T Cells for Lupus

Overseen By Matthew A Spear, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Luminary Therapeutics

Must be taking: Corticosteroids, Hydroxychloroquine

Must not be taking: High dose steroids

Disqualifiers: Neuropsychiatric lupus, Active infection, HIV, Genetic syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 14

Duration: 14 days per dose level

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called LMY-920, a type of CAR-T cell therapy, for individuals with systemic lupus erythematosus (SLE) that does not respond to standard treatments. The main goal is to determine the treatment's safety and identify the right dose for future studies, with the hope of reducing disease symptoms. Individuals with active SLE, despite using common medications like corticosteroids or hydroxychloroquine, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you stop T cell targeted therapy more than 3 weeks before starting and reduce prednisone to 10 mg/day or less. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that LMY-920 is likely to be safe for humans?

Research has shown that CAR T-cell therapies have successfully treated some cancers. This success gives researchers hope that similar treatments, like BAFF CAR-T cells, could benefit conditions such as lupus. In past studies with different CAR T-cells, patients generally tolerated the treatment well. Although some side effects occurred, they were usually manageable.

Since this trial is in the early stages, data on the safety of BAFF CAR-T cells for lupus remains limited. However, testing in humans suggests some confidence in its safety. Ensuring participant safety is a top priority, and this trial will focus on confirming the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus?

Unlike the standard treatments for lupus, which often include immunosuppressive drugs and corticosteroids, LMY-920 offers a unique approach by using BAFF CAR-T cell therapy. This treatment is exciting because it harnesses the power of the patient's own immune cells, which are modified to specifically target and destroy harmful cells that drive the disease. This targeted action means it could potentially offer more precise and effective results with fewer side effects compared to traditional therapies. Researchers are particularly enthusiastic about this approach because it represents a novel mechanism of action that could transform how lupus is managed, focusing on long-term remission rather than just symptom control.

What evidence suggests that BAFF CAR-T cells might be an effective treatment for lupus?

Studies have shown that CAR T-cell therapy can greatly improve the health of people with systemic lupus erythematosus (SLE). This treatment teaches the immune system to identify and reduce specific cells that cause the disease. Research indicates that patients receiving CAR T-cell therapy have experienced significant improvements in their symptoms and blood tests. Traditional treatments often struggle to provide lasting relief in SLE, but CAR T-cell therapy offers a promising new option. Early findings suggest that BAFF CAR-T cells, like those studied in this trial, could effectively manage SLE symptoms. ^{1 2 3 5 6}

Who Is on the Research Team?

Dean Lee, PhD

Principal Investigator

Nationwide Children

Are You a Good Fit for This Trial?

This trial is for adults aged 18-69 with active systemic lupus erythematosus (SLE) who haven't responded to standard treatments like corticosteroids and hydroxychloroquine, or other drugs such as methotrexate. Participants must have a creatinine clearance of at least 30 ml/min, stable heart function with an ejection fraction ≥40%, good lung function (pulse oximetry ≥92% on room air), and liver enzymes within acceptable limits.

Inclusion Criteria

My condition did not improve after standard and additional treatments.

I rely on steroids for my condition.

I am taking specific medications but my disease is still active because I can't tolerate standard treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous BAFF CAR-T cells with dose escalation to determine the maximum tolerated dose

14 days per dose level

Staggered enrollment with safety monitoring every 14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• LMY-920

Trial Overview The study is testing the safety and optimal dose for phase 2 of LMY-920, which are CAR-T cells targeting BAFF-ligand in patients with refractory SLE. The goal is to see if these modified immune cells can safely improve disease activity scores in SLE patients.

How Is the Trial Designed?

Group I: BAFF CAR T Experimental Treatment 1 Intervention

Autologous BAFF CAR T Therapy

Who Is Running the Clinical Trial?

Luminary Therapeutics

Lead Sponsor

Trials

3

Recruited

70+

Nationwide Children

Collaborator

Trials

2

Recruited

50+

Published Research Related to This Trial

In a study of 52 patients with systemic lupus erythematosus (SLE), researchers identified a significantly expanded population of PD-1hiCXCR5-CD4+ T peripheral helper (Tph) cells that are linked to B cell activation and disease activity.

The presence of Tph cells correlated with clinical disease severity and B cell numbers in the kidneys of SLE patients, indicating their potential as a target for therapies aimed at modulating harmful B cell responses in this autoimmune disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21. Bocharnikov, AV., Keegan, J., Wacleche, VS., et al.[2022]

Anti-CD19 CAR-T cell therapy demonstrated effective B-cell depletion in a mouse model of systemic lupus erythematosus (SLE), showing both preventive and therapeutic benefits against the disease.

CAR-T cells using the 4-1BB costimulatory motif were found to be more effective than those using the CD28 motif, suggesting a promising strategy for optimizing treatment in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Jin, X., Xu, Q., Pu, C., et al.[2022]

In a study of six patients with refractory systemic lupus erythematosus (SLE), anti-CD19 CAR T cell therapy was found to be well tolerated and led to a significant reduction in inflammatory cytokines IL-6 and TNFα three months after treatment.

The therapy also resulted in a marked decrease in SLE-associated antibodies in five out of six patients, suggesting a potential mechanism for its efficacy in managing SLE symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Nunez, D., Patel, D., Volkov, J., et al.[2023]

Complete and sustained depletion of CD19+ B cells using CD19-targeted CAR T cells was shown to be a highly effective therapy in lupus models, significantly reversing disease symptoms and extending lifespan in mouse models of lupus.

This approach demonstrated long-lasting effects, with CAR T cells remaining active for up to one year, suggesting that sustained B cell depletion could be a promising strategy for treating lupus in humans, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Kansal, R., Richardson, N., Neeli, I., et al.[2021]

Using CAR T cells to continuously deplete B cells leads to remission of lupus symptoms in mice that are genetically predisposed to the disease, suggesting a potential therapeutic strategy for lupus.

This study highlights the effectiveness of targeted cell therapy in managing autoimmune diseases, demonstrating that manipulating the immune system can result in significant health improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slamming the brakes on lupus with CAR T cells. Clark, RA.[2019]

In a small study of five treatment-resistant patients with systemic lupus erythematosus (SLE), CD19 CAR T cell therapy led to significant clinical improvements and remission in all participants after 3 months, demonstrating its potential efficacy.

The treatment was well tolerated, with only mild cytokine release syndrome reported, suggesting a favorable safety profile for this innovative therapy in seriously ill SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. Boulougoura, A., Gendelman, H., Surmachevska, N., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06340750?cond=Lupus%20Erythematosus&aggFilters=status:rec&country=United%20States&locStr=United%20States&viewType=Table&rank=10

BAFF CAR-T Cells (LMY-920) for Systemic Lupus Erythematosus The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/470955

BAFF CAR-T Cells (LMY-920) for Systemic Lupus ... This phase 1 study seeks to examine the safety and recommended phase 2 dose (RP2D) of BAFF-ligand CAR-T cells (LMY-920) in adult patients ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S004901722500157X

CAR T-cell therapy in SLE: A systematic review Chimeric antigen receptor (CAR) T-cell therapy is poised to revolutionize the treatment of systemic lupus erythematosus (SLE). Following the landmark study by ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12123052/

Baby you can drive my CAR-T cells - PMC CAR-T therapy could significantly improve SLE outcomes. Demonstrating remarkable clinical and serologic improvements in SLE patients.

5. link.springer.com link.springer.com/article/10.1007/s00210-025-04425-z

CAR T cell therapy efficacy & safety in SLE Conventional therapies for systemic lupus erythematosus (SLE) often fail to achieve lasting remission. CAR T cell therapy, which depletes ...

6. trialx.com trialx.com/clinical-trials/listings/322825/baff-car-t-cells-lmy-920-for-systemic-lupus-erythematosus/

BAFF CAR-T Cells (LMY-920) for Systemic Lupus ... This phase 1 study seeks to examine the safety and recommended phase 2 dose (RP2D) of BAFF-ligand CAR-T cells (LMY-920) in adult patients with ...