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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a new cell therapy, called CAR T therapy (also known as KYV-101 or Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy), can help treat dermatomyositis, an autoimmune condition that causes inflammation in the skin, muscles, and lungs. CAR T therapy modifies certain white blood cells to attack and reduce harmful cells contributing to the disease. The trial will assess how well patients tolerate the treatment and whether it alleviates symptoms. This trial seeks adults with moderate-to-severe dermatomyositis who have not responded to other treatments. As a Phase 1 trial, this 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 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.

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

Research has shown that KYV-101, a type of CAR T therapy, holds promise in treating other conditions by targeting a protein called CD19 on certain white blood cells. This represents a new method for treating dermatomyositis, an autoimmune disease.

In studies of similar CAR T therapies, many patients tolerated the treatment well, though some experienced side effects. These side effects can include fever, low blood pressure, or changes in blood cell counts, and they are often manageable with medical care. It is important to note that KYV-101 remains in early testing stages, so more research is needed to fully understand its safety for dermatomyositis.

Prospective trial participants should discuss the potential risks and benefits with a healthcare professional. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for dermatomyositis?

Unlike the standard treatments for dermatomyositis, which typically involve immunosuppressive drugs and corticosteroids, KYV-101 is unique because it uses CAR T cell therapy to target the CD19 antigen. This approach is exciting because it involves genetically modifying a patient's own T cells to better recognize and attack cells contributing to the disease. Researchers are hopeful that this targeted mechanism will provide a more precise and potentially more effective treatment option, reducing the need for long-term use of medications with broad and often harsh side effects.

What evidence suggests that CAR T therapy might be an effective treatment for dermatomyositis?

Research shows that CAR T therapy, specifically KYV-101, may hold promise for treating dermatomyositis. In this trial, participants will receive an infusion of autologous, genetically modified CAR T cells targeting the CD19 antigen. This treatment alters a type of white blood cell to locate and destroy B cells, which are believed to contribute to the disease. Studies have found that targeting the CD19 protein on B cells can reduce harmful antibodies that attack the body's tissues. Early results in similar conditions suggest this method might reduce inflammation and improve symptoms. Although human studies provide limited information, this approach shows potential for aiding autoimmune conditions like dermatomyositis. ^{1 3 4 5 6}

Who Is on the Research Team?

Everett Meyer, MD

Principal Investigator

Stanford University

David Fiorentino, MD, PhD

Principal Investigator

Stanford University

Lorinda Chung, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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.

Findings of muscular inflammation or myopathy other than the indication

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06298019?term=AREA%5BConditionSearch%5D(%22Dermatomyositis%22)&rank=2

NCT06298019 | Study of KYV-101 Anti-CD19 CAR T ... The goal of this clinical trial is to characterize to understand the effects of a type of cell therapy called Chimeric Antigen Receptor T lymphocyte (CAR T) ...

2. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/s/NCT06298019.html

Study of KYV-101 Anti-CD19 CAR T Therapy in Adult ... The goal of this clinical trial is to characterize to understand the effects of a type of cell therapy called Chimeric Antigen Receptor T lymphocyte (CAR T) ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06702

Autologous Fully-Human Anti-CD19 Chimeric Antigen ... This phase I trial studies the safety and side effects of autologous fully-human anti-CD19 chimeric antigen receptor T-cell (KYV-101) and to see how well it ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07161193

NCT07161193 | Anti-CD19 Chimeric Antigen Receptor T ... The primary endpoint is to evaluate the incidence and severity of cytokine release syndrome and severe neurotoxic adverse events within 28 days ...

5. kyvernatx.com kyvernatx.com/education-events/publications/

CAR T-Cell Therapy Publications Activity and Manufacturing of KYV-101 Anti-CD19 Chimeric Antigen Receptor T Cells Derived from Patients With Neurologic Autoimmune Diseases.

6. stanfordhealthcare.org stanfordhealthcare.org/trials/s/NCT06298019.html

Study of KYV-101 Anti-CD19 CAR T Therapy in Adult ... The goal of this clinical trial is to characterize to understand the effects of a type of cell therapy called Chimeric Antigen Receptor T lymphocyte (CAR T) ...