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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for Systemic Lupus Erythematosus (SLE), a condition where the immune system attacks healthy tissues, particularly in individuals whose current treatments are ineffective. The treatment, known as SCRI-CAR19v3 or CD19-specific CAR T cell therapy, uses modified T cells, a type of white blood cell, to target and destroy harmful B cells. This early-stage trial aims to determine if the approach is safe and effective. Ideal candidates are children or young adults with SLE that does not respond to standard treatments and can undergo apheresis, a process that collects blood cells. 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 innovative therapy.

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.

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

Research has shown that a treatment called CD19-specific CAR T cell therapy, such as SCRI-CAR19v3, has been tested in people with systemic lupus erythematosus (SLE). In these studies, participants generally tolerated the treatment well, experiencing only mild side effects like a temporary immune response known as mild cytokine release syndrome. This suggests the treatment might be safe for humans. However, since this trial is in an early stage, it primarily focuses on assessing safety. While the initial results are promising, further research is needed to fully understand the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about SCRI-CAR19v3 for lupus because it uses a cutting-edge approach called CAR-T cell therapy. Unlike traditional treatments like corticosteroids or immunosuppressants, which broadly dampen the immune system, SCRI-CAR19v3 specifically reprograms a patient's own immune cells to target and destroy the problematic cells causing lupus. This precision can potentially lead to fewer side effects and more effective long-term control of the disease. By honing in on the disease at a cellular level, SCRI-CAR19v3 offers a promising new avenue for treating lupus that could revolutionize care for patients.

What evidence suggests that SCRI-CAR19v3 might be an effective treatment for lupus?

Research has shown that CD19-specific CAR T-cell therapy, which participants in this trial will receive as SCRI-CAR19v3, effectively treats patients with lupus who haven't responded to other treatments. In these studies, patients experienced significant improvements both in the short term and over the long term. For example, 87.5% of patients did not have any flare-ups over two years. This treatment targets and reduces certain B cells that contribute to lupus. Overall, CAR T-cell therapy shows strong promise for those struggling with lupus. ^{1 3 4 6 7}

Who Is on the Research Team?

Shaun Jackson, MD

Principal Investigator

Seattle Children's Hospital

Colleen Annesley, MD

Principal Investigator

Seattle Children's Hospital

Corinne Summers, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694027/

CAR T-cell therapy for systemic lupus erythematosus Ultimately, 8 patients (20%) achieved disease control, and 35 (87.5%) experienced no flare-ups over a median 2-year follow-up, suggesting improved disease ...

2. withpower.com withpower.com/trial/phase-1-lupus-erythematosus-systemic-6-2024-fd505

Cell Therapy for Lupus · Recruiting Participants for Phase ... 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 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1568997224001782

Harnessing the potential of CAR-T cell in lupus treatment All clinical data reported in SLE patients so far showed that autologous anti-CD19 CAR T-cell treatment allowed impressive short- and longer-term resolution of ...

4. jrheum.org jrheum.org/content/52/Suppl_1/147.3

A PHASE 1, MULTICENTER, OPEN-LABEL STUDY OF CB ... Background/Purpose Autologous CD19-directed CAR-T cell therapy led to deep depletion of aberrant B cells in lupus patients, leading to prolonged ...

5. labiotech.eu labiotech.eu/in-depth/car-t-cell-therapy-lupus/

CAR-T cell therapy for lupus: An emerging field with great ... CAR-T cell therapy could be effective in treating systemic lupus erythematosus, interest in the field quickly took off.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/503155

REACT-01: Reversing Autoimmunity Through Cell Therapy This is a phase 1, open-label, non-randomized study enrolling pediatric and young adult research participants with treatment-refractory ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06121297

RESET-SLE: A Phase 1/2 Open-Label Study to Evaluate ... This study is being conducted to evaluate the safety and efficacy of an investigational cell therapy, CABA-201, that can be given to patients with either LN or ...