CART19 for Lupus

Overseen By Melissa Varghese

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital of Philadelphia

Must be taking: Immunosuppressive agents

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CART19 for children and young adults with difficult-to-treat lupus. The goal is to determine if CART19 is safe and effective for those whose lupus has not improved with regular treatments. CART19 uses modified immune cells to target and help control lupus symptoms. Individuals with active lupus despite at least three months of conventional treatments might be suitable candidates for this trial. As a Phase 1/Phase 2 trial, this research focuses on understanding how CART19 works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

Participants will need to stop taking certain immunosuppressive medications before the T cell collection and CART19 infusion. However, anti-malarial drugs for SLE and some other medications like physiologic replacement hydrocortisone or inhaled steroids are allowed.

Is there any evidence suggesting that CART19 is likely to be safe for humans?

Research has shown that CART19, a type of CAR-T cell therapy, is generally safe for patients with severe and hard-to-treat systemic lupus erythematosus (SLE). Studies have found that this treatment is effective and usually well-tolerated. In one study, individuals with SLE experienced fewer serious side effects compared to those receiving similar treatments for other conditions, such as certain blood cancers. Most patients had mild to moderate side effects, which were manageable. These findings suggest that CART19 could be a promising option for those with difficult-to-treat SLE, offering a good balance of safety and potential benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard lupus treatments, which often include immunosuppressive drugs like corticosteroids and antimalarials, CART19 offers a novel approach by using genetically modified T-cells to target the CD19 protein on B-cells. This treatment is unique because it involves reprogramming a patient's own immune cells to specifically attack and destroy the problematic B-cells that drive lupus. Researchers are excited about CART19 because it has the potential to provide a more targeted and long-lasting effect, reducing the need for continuous medication and minimizing side effects associated with traditional therapies.

What evidence suggests that CART19 might be an effective treatment for lupus?

Research has shown that CART19, a type of CAR T cell therapy, could help treat severe and hard-to-treat systemic lupus erythematosus (SLE). Studies have found that this therapy is safe and can effectively lead to remission, meaning the disease becomes inactive. In one study, 81% of patients achieved a state called lupus low disease activity, indicating significant symptom improvement. Another study demonstrated major improvements in patients treated with CART19. These findings suggest that CART19 could be a strong option for managing difficult cases of SLE. Participants in this trial will receive CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection. ^{1 2 3 4 6}

Who Is on the Research Team?

Caitlin Elgarten, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for children and young adults with refractory Systemic Lupus Erythematosus (SLE), including those diagnosed with lupus nephritis. Participants must meet certain health criteria to be eligible, but specific inclusion and exclusion details are not provided.

Inclusion Criteria

Meeting ACR/EULAR Classification Criteria for SLE

I am between 12 and 29 years old.

My organs are working well.

Exclusion Criteria

I am HIV positive.

I have active Hepatitis B.

I have Hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including dose limiting toxicities and other secondary outcomes

24 months

What Are the Treatments Tested in This Trial?

Interventions

• CART19

Trial Overview The study is testing CART19, a type of cell therapy aimed at treating SLE. It's an early-phase trial assessing safety in phase 1 without increasing doses, followed by efficacy and continued safety evaluation in phase 2.

How Is the Trial Designed?

Group I: CART19 Experimental Treatment 1 Intervention

Participants will receive the study product. CART19 cells transduced with a lentiviral vector to express anti-CD19 scFv:41-BB:TCRζ, administered by IV injection.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

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]

A patient with severe antisynthetase syndrome, unresponsive to standard therapies, showed rapid clinical improvement after receiving CD19-targeting CAR T cells, with significant enhancements in muscle and lung function observed over eight months.

The treatment not only normalized various inflammatory markers and muscle enzymes but also indicated a reset of B-cell immunity, suggesting that CD19-targeting CAR T cells can effectively address both B- and T-cell involvement in autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome. Pecher, AC., Hensen, L., Klein, R., et al.[2023]

In a study involving five patients with severe systemic lupus erythematosus (SLE), treatment with CAR T cells targeting CD19 led to complete remission of the disease in all participants after 3 months, demonstrating high efficacy.

The CAR T cell therapy was well tolerated, with only mild side effects, and patients maintained drug-free remission for an average of 8 months, even after B cells reappeared, indicating a durable response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Mackensen, A., Müller, F., Mougiakakos, D., 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36109639/

Anti-CD19 CAR T cell therapy for refractory systemic lupus ... These data suggest that CD19 CAR T cell transfer is feasible, tolerable and highly effective in SLE.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S266663402500176X

Allogeneic CD19-targeted CAR-T therapy in refractory ... In patients with severe and refractory SLE, allogeneic CAR-T cell therapy showed profound safety and clinical efficacy for disease remission.

3. nature.com nature.com/articles/s41422-025-01128-1

Allogeneic anti-CD19 CAR-T cells induce remission in ... In this study, we demonstrated that an allogeneic CD19-targeted CAR-T cell therapy is effective and safe in treating relapsed/refractory SLE.

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

CAR T cell therapy efficacy and safety in SLE: a systematic ... Among those patients, 81% achieved lupus low disease activity state (LLDAS) with improvements in disease activity and serologic markers. B cell ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06222853

NCT06222853 | Study of Therapeutic Efficacy of Anti-CD19 ... The purpose of this study is to assess the safety and efficacy of the anti-CD19 CAR-T cells in the treatment of refractory SLE. Official Title. A Clinical Study ...

6. ashpublications.org ashpublications.org/blood/article/146/9/1088/537757/Comparison-of-the-safety-profiles-of-CD19

Comparison of the safety profiles of CD19-targeting CAR T ... Despite similar CAR T-cell dynamics, patients with SLE experienced less severe adverse events after CAR T-cell therapy than those with B-NHL ...