Cell Therapy for Lupus

Overseen By Shaun Jackson, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Disqualifiers: CNS lupus, Kidney dysfunction, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants stop certain medications before enrolling. You must be at least 24 weeks past your last Rituximab treatment, 12 weeks past Belimumab or Anifrolumab, and 4 weeks past any calcineurin inhibitor. If you're on other immunosuppressive or corticosteroid therapies, you need to be on a stable dose for a certain period before joining.

What data supports the effectiveness of the treatment SCRI-CAR19v3, CD19-specific CAR T cell therapy for lupus?

Research shows that CD19-specific CAR T cell therapy has been effective in patients with lupus who did not respond to other treatments. In studies, patients experienced significant improvement in symptoms and achieved remission, with the treatment being well tolerated. ^{1 2 3 4 5}

Is CD19-specific CAR T cell therapy safe for humans?

CD19-specific CAR T cell therapy has been tested in patients with systemic lupus erythematosus (SLE) and was generally well tolerated, with only mild cytokine-release syndrome (a mild immune reaction) reported. This suggests that the treatment is feasible and tolerable in humans. ^{1 2 3 4 6}

How is the treatment SCRI-CAR19v3 different from other treatments for lupus?

SCRI-CAR19v3 is a unique treatment for lupus because it uses CAR T cells, which are specially modified immune cells, to target and deplete B cells that contribute to the disease. This approach is different from traditional lupus treatments, as it offers a more targeted and potentially long-lasting effect, leading to drug-free remission in some patients. ^{1 2 3 4 7}

What is the purpose of this trial?

This is a phase 1, open-label, non-randomized study enrolling pediatric and young adult research participants with treatment-refractory Systemic Lupus Erythematosus (SLE), to examine the safety, feasibility, and efficacy of administering T cell products derived from peripheral blood mononuclear cells (PBMC) that have been genetically modified to express CD19 specific chimeric antigen receptor (CAR) A child or young adult meeting all eligibility criteria and meeting none of the exclusion criteria will have their T cells collected. The T cells will then be bioengineered into a CAR T cell that targets circulating and tissue residing B cells.

Research Team

Colleen Annesley, MD

Principal Investigator

Seattle Children's Hospital

Shaun Jackson, MD

Principal Investigator

Seattle Children's Hospital

Corinne Summers, MD

Principal Investigator

Seattle Children's Hospital

Eligibility Criteria

This trial is for children and young adults with severe Systemic Lupus Erythematosus (SLE) that hasn't improved with treatment. Participants will have their T cells collected and modified to target B cells related to SLE.

Inclusion Criteria

I've been on a stable dose of non-calcineurin immunosuppressants for 8 weeks or more.

I can undergo apheresis or already have an apheresis product ready for use.

I have been on a stable dose of corticosteroids for at least 2 weeks.

Exclusion Criteria

I have or had lupus or another disease affecting my brain.

I need dialysis for my kidney condition.

I had cancer before, but it has been treated and there's been no sign of it for less than 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

T Cell Collection and Engineering

T cells are collected from participants and bioengineered into CAR T cells targeting B cells

4 weeks

Treatment

Single infusion of SCRI-CAR19v3 CAR T cells

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Regular monitoring visits

Treatment Details

Interventions

• SCRI-CAR19v3

Trial Overview The study tests a new therapy called SCRI-CAR19v3, where participants' own T cells are engineered to fight lupus by targeting CD19 on B cells. It's an early-stage trial focusing on safety and how well the treatment works.

Participant Groups

Group I: SCRI-CAR19v3 Experimental Treatment 1 Intervention

Single infusion of SCRI-CAR19v3

SCRI-CAR19v3 is already approved in United States for the following indications:

Approved in United States as SCRI-CAR19v3 for:

• Systemic Lupus Erythematosus (SLE)

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Findings from Research

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]

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 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]

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]

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]

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]

CAR T therapy, known for its success in treating blood cancers, has been applied to systemic lupus erythematosus in a small study involving five patients, indicating its potential beyond cancer treatment.

The findings from Mackensen et al. suggest that CAR T therapy could be a promising new approach for autoimmune diseases, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T therapy extends its reach to autoimmune diseases. Baker, DJ., June, CH.[2023]

References

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

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

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

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

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

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. [2023]

4. China pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

CAR T therapy extends its reach to autoimmune diseases. [2023]