CAR T Therapy for Dermatomyositis

Recruiting at 1 trial location

Overseen By Lori Panu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Must not be taking: Antidepressants, others

Disqualifiers: Severe muscle damage, HIV, 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: 1

Duration: 1 week

21 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants must be unable to washout or interrupt autoimmune disease therapy prior to apheresis, which suggests that some medications may need to be paused or adjusted. It's best to discuss your specific medications with the trial team.

What is the safety profile of CAR T-cell therapy in humans?

CAR T-cell therapy, including treatments like KYV-101, has been associated with several side effects, such as cytokine release syndrome (a severe immune reaction), neurological issues, blood disorders, infections, and heart problems. While these side effects can be serious, they are not always fatal, and careful monitoring is required, especially in the week following treatment. ^{1 2 3 4 5}

How is the treatment KYV-101 different from other treatments for dermatomyositis?

KYV-101 is a CAR T-cell therapy, which is a type of treatment that uses specially modified immune cells to target and destroy specific cells in the body. This approach is unique compared to traditional treatments for dermatomyositis, which often involve immunosuppressive drugs or topical therapies. ^{6 7 8 9 10}

What is the purpose of this trial?

This trial tests a new therapy in adults with dermatomyositis. The therapy modifies their white blood cells to target and destroy harmful B cells, aiming to reset their immune system and reduce disease symptoms. This new treatment shows promising results in similar conditions.

Research Team

Everett Meyer, MD

Principal Investigator

Stanford University

David Fiorentino, MD, PhD

Principal Investigator

Stanford University

Lorinda Chung, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults with dermatomyositis, an autoimmune disease. Participants must have their own T cells modified to target B cells that may be causing the disease. It's not specified who can't join, but typically those with other serious health issues or immune deficiencies might be excluded.

Inclusion Criteria

My muscle disease is active, confirmed by blood tests or recent scans.

Subject must sign a written ICF prior to any screening procedures

I have a condition that didn't improve after using steroids and two other immune treatments for 3 months.

Exclusion Criteria

I have heart problems that affect my daily activities.

I have had cellular immunotherapy or gene therapy before.

I have severe muscle damage, may use a wheelchair, and have a specific lung condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of autologous, genetically modified CAR T cells specific for the CD19 antigen

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Regular visits (frequency not specified)

Treatment Details

Interventions

• KYV-101

Trial Overview The study tests KYV-101 Anti-CD19 CAR T Therapy in adults with dermatomyositis. Patients' T cells are engineered to destroy B cells by recognizing CD19 protein, potentially resetting the immune system and alleviating the disease.

Participant Groups

Group I: Active Intervention with CAR T Experimental Treatment 1 Intervention

All participants in the trial will receive an infusion of autologous, genetically modified CAR T cells specific for the CD19 antigen

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?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

CD19-CAR T cell therapy is feasible and safe for treating children and young adults with refractory B-cell malignancies, with a maximum tolerated dose established at 1×10^6 CAR T cells per kg.

The treatment showed potent anti-leukaemic activity, with all toxicities being fully reversible, including severe cases of cytokine release syndrome in 14% of patients, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lee, DW., Kochenderfer, JN., Stetler-Stevenson, M., et al.[2022]

Chimeric-antigen-receptor T cells (CAR-T) targeting CD19 are associated with several adverse drug reactions (ADRs), with the most common being cytokine release syndrome (CRS), neurological disorders, and hematological disorders, as identified in a study analyzing 1783 safety reports.

While CAR-T therapy can lead to severe ADRs, particularly in the week following administration, the overall fatality rate from these reactions is relatively low at 5.5%, though serious conditions like hemophagocytic-lymphohistiocytosis and infections require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. Dolladille, C., Ederhy, S., Ezine, E., et al.[2021]

CAR-T therapy is highly effective in treating certain cancers, but it is associated with significant complications, particularly cytokine release syndrome and neurotoxicity.

In addition to the well-known side effects, there are various other CAR-T-specific adverse events that require careful management based on clinical experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events of CAR-T therapy]. Arai, Y.[2023]

In a review of 996 adverse events related to CAR T cell therapy from 2017 to 2019, 19.7% were cardiovascular events (CVEs), with arrhythmias being the most common, indicating a significant risk associated with this treatment.

Patients experiencing CVEs had a higher mortality rate of 30.1%, highlighting the need for careful monitoring for cardiovascular issues, especially in those also presenting with neurotoxicity or cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. Guha, A., Addison, D., Jain, P., et al.[2021]

CAR T-cell therapy can lead to significant toxicities, particularly cytokine release syndrome (CRS) and neurologic toxicities, which require careful monitoring and management.

Recent guidelines and evidence-based practices are evolving to help healthcare professionals, especially nurses, effectively assess and manage these toxicities to ensure patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associated Toxicities: Assessment and Management Related to CAR T-Cell Therapy. Anderson, K., Latchford, T.[2020]

References

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

T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. [2022]

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

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. [2021]

3. Japan pubmed.ncbi.nlm.nih.gov

[Management of adverse events of CAR-T therapy]. [2023]

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

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. [2021]

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

Associated Toxicities: Assessment and Management Related to CAR T-Cell Therapy. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Cutaneous dermatomyositis in the era of biologicals. [2018]

7. Canada pubmed.ncbi.nlm.nih.gov

Cyclosporin a therapy in refractory juvenile dermatomyositis. Experience and longterm followup of 6 cases. [2015]

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

Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Topical tacrolimus 0.1% ointment for refractory skin disease in dermatomyositis: a pilot study. [2019]

10. Scotland pubmed.ncbi.nlm.nih.gov

Dermatomyositis-polymyositis in children. [2017]