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

Trial Summary

What is the purpose of this trial?

This is a single-center, single-arm, open-label phase 1/2 study of CART19 in children and young adults with refractory Systemic lupus erythematosus (SLE), including both patients diagnosed with lupus nephritis (LN) and patients with non-renal Systemic lupus erythematosus (SLE). Phase 1 will evaluate the safety of CART19 in 6-12 patients with Systemic lupus erythematosus (SLE). There is no planned dose escalation, but a dose de-escalation will be made based on the incidence of Dose Limiting Toxicities. Phase 2 will evaluate the efficacy and further evaluate the safety of CART19 in this population.

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.

How is the CART19 treatment different from other treatments for lupus?

CART19 treatment is unique because it uses modified immune cells called CAR T cells to target and eliminate specific B cells that contribute to lupus, offering a more sustained and effective approach compared to traditional therapies that may not fully deplete these cells. ^{1 2 3 4 5}

Research Team

Caitlin Elgarten, MD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. [2023]

3. China pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. [2021]