CD19 CAR T-Cell Therapy for Scleroderma

Recruiting at 1 trial location

Overseen By Kyverna Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Kyverna Therapeutics

Disqualifiers: HIV, Hepatitis B/C, Neurologic disorders, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

21 Participants Needed

Trial Summary

What is the purpose of this trial?

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects with Systemic Sclerosis

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment KYV-101, Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy, for Scleroderma?

Research shows that anti-CD19 CAR T-cell therapy has been effective in treating B-cell cancers by targeting CD19, a protein found on cancerous B cells, leading to long-term remissions in some patients. This suggests that the therapy has potent activity against cells expressing CD19, which could potentially be beneficial in other conditions where CD19 is involved. ^{1 2 3 4 5}

How is the CD19 CAR T-Cell treatment for scleroderma different from other treatments?

CD19 CAR T-Cell therapy is unique because it uses genetically modified T cells to target and destroy B cells, which are involved in autoimmune diseases like scleroderma. This approach is novel compared to traditional treatments, as it directly modifies the immune system to reduce disease activity and has shown promise in similar autoimmune conditions like systemic lupus erythematosus. ^{1 6 7 8 9}

Research Team

MD

Principal Investigator

Kyverna Therapeutics, Inc.

Eligibility Criteria

This trial is for people with a condition called systemic sclerosis, specifically the diffuse cutaneous type. They should be within 6 years of their first symptom that's not Raynaud's phenomenon and have active disease. Participants must also be current on vaccinations recommended for those with weakened immune systems.

Inclusion Criteria

Up to date on all recommended vaccinations per CDC or institutional guidelines for immune-compromised individuals

My skin condition was diagnosed as diffuse cutaneous SSc within the last 6 years and is still active.

I have been diagnosed with systemic sclerosis.

Exclusion Criteria

I have a serious lung condition.

I have previously received CAR-T or gene therapy.

I have had a stem cell transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion Conditioning

Participants undergo lymphodepletion conditioning prior to receiving KYV-101 CAR T cells

1-2 weeks

Treatment

Participants receive KYV-101 CAR T-cell therapy

52 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• KYV-101

Trial Overview The study is testing KYV-101, which is a type of CAR T-cell therapy targeting CD19, an antigen found on certain cells in the body. This therapy will be compared to or combined with standard treatments that reduce the number of lymphocytes (a type of white blood cell).

Participant Groups

Group I: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 2) Experimental Treatment 2 Interventions

Recommended Phase 2 Dose

Group II: KYV-101 CAR-T cells with lymphodepletion conditioning (Phase 1) Experimental Treatment 2 Interventions

Dosing with KYV-101 CAR T cells

KYV-101 is already approved in United States for the following indications:

Approved in United States as KYV-101 for:

• Refractory Lupus Nephritis
• Stiff-Person Syndrome
• Myasthenia Gravis
• Diffuse Cutaneous Systemic Sclerosis (Scleroderma)
• Primary and Secondary Progressive Multiple Sclerosis

Who Is Running the Clinical Trial?

Kyverna Therapeutics

Lead Sponsor

Trials

11

Recruited

320+

Findings from Research

Anti-CD19 CAR T cell therapy has shown promising results in treating advanced-stage B-cell malignancies, with some patients achieving long-term remissions after treatment, indicating its potential as a new standard therapy.

While the therapy demonstrates strong efficacy by specifically targeting CD19, some patients have experienced acute adverse effects linked to increased inflammatory cytokines, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Kochenderfer, JN., Rosenberg, SA.[2021]

The phase I/IIa trial of third-generation CAR T-cell therapy targeting CD19 in 15 patients with B-cell malignancies showed that the treatment was generally safe, with only 4 patients requiring hospitalization due to adverse reactions.

Six out of 15 patients achieved complete responses, indicating promising efficacy, particularly in those with a good immune status prior to treatment, suggesting that immune profiling could help identify potential responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Enblad, G., Karlsson, H., Gammelgård, G., et al.[2019]

A new fusion protein, CD19sIg1-4, was developed to specifically detect anti-CD19 CAR expression in T-cells, showing effective binding in ELISA assays and enabling sensitive flow cytometry analysis.

This reagent can identify CAR-modified T-cells with high specificity and low background, allowing for better monitoring of CAR T-cell therapies targeting B-lineage malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CD19/Fc fusion protein for detection of anti-CD19 chimeric antigen receptors. De Oliveira, SN., Wang, J., Ryan, C., et al.[2021]

Allogeneic CD19 CAR T cells can effectively target lymphoma without significantly increasing the risk of graft-versus-host disease (GVHD), as shown in mouse models of allo-HSCT and lymphoma.

The study found that enhanced stimulation of alloreactive T cells with CD28-costimulated CD19 CARs leads to their clonal deletion and reduced effector function, which helps prevent GVHD while maintaining anti-lymphoma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. Ghosh, A., Smith, M., James, SE., et al.[2023]

Adoptive T-cell therapy using anti-CD19 chimeric antigen receptor (CAR)-expressing T cells showed strong effectiveness in eliminating lymphoma cells in a murine model, with complete eradication of normal B cells lasting for at least 143 days after treatment.

The success of the anti-CD19-CAR-transduced T cells in fighting lymphoma was significantly enhanced by pre-treatment irradiation of the mice, and these CAR T cells outperformed the original anti-CD19 monoclonal antibody in terms of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Kochenderfer, JN., Yu, Z., Frasheri, 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]

CD19-targeted CAR Tregs, generated from human peripheral blood mononuclear cells, can be expanded in the lab while retaining their regulatory properties, making them a promising option for therapy in autoimmune diseases.

These CAR Tregs effectively suppress antibody production and B cell differentiation through a TGF-β-dependent mechanism, potentially reducing the risk of graft-versus-host disease compared to conventional CAR T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD. Imura, Y., Ando, M., Kondo, T., et al.[2021]

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 therapies have shown promise in treating aggressive B-cell lymphomas that are resistant to conventional therapies, achieving durable remissions in 33%-40% of patients with relapsed or refractory disease.

While these therapies can lead to significant side effects like cytokine release syndrome and neurologic toxicities, these are generally manageable and reversible, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapies for Aggressive B-Cell Lymphomas: Current and Future State of the Art. Abramson, JS., Lunning, M., Palomba, ML.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. [2021]

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

A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. [2019]

3. England pubmed.ncbi.nlm.nih.gov

A CD19/Fc fusion protein for detection of anti-CD19 chimeric antigen receptors. [2021]

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

Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. [2023]

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

Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. [2023]

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

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

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

CD19-targeted CAR regulatory T cells suppress B cell pathology without GvHD. [2021]

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

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

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

Chimeric Antigen Receptor T-Cell Therapies for Aggressive B-Cell Lymphomas: Current and Future State of the Art. [2021]