CD-19 CAR T for Stiff Person Syndrome

Recruiting at 2 trial locations

Overseen By Kyverna Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kyverna Therapeutics

Disqualifiers: Stroke, Seizure, Dementia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

25 Participants Needed

Trial Summary

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 CD-19 CAR T for Stiff Person Syndrome?

CD19 CAR T-cell therapy has shown significant success in treating certain blood cancers, like B-cell non-Hodgkin lymphoma and acute lymphoblastic leukemia, with high rates of complete remission in patients. This suggests potential effectiveness in other conditions, although specific data for Stiff Person Syndrome is not available. ^{1 2 3 4 5}

How is CD19 CAR T-cell therapy different from other treatments for Stiff Person Syndrome?

CD19 CAR T-cell therapy is unique because it uses genetically modified T-cells to target specific proteins on cells, a method primarily used for certain blood cancers, and it represents a novel approach for treating Stiff Person Syndrome, which lacks standard treatments. ^{3 5 6 7 8}

What is the purpose of this trial?

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Subjects With Treatment Refractory Stiff Person Syndrome

Research Team

MD

Principal Investigator

Kyverna Therapeutics

Eligibility Criteria

This trial is for people with Stiff Person Syndrome who haven't improved after at least one immunomodulatory therapy. They should experience spasms triggered by noise, touch, or stress and have high levels of specific antibodies in their blood or CSF. Participants need to be able to walk and not have any other neurological diseases causing stiffness.

Inclusion Criteria

My muscles are constantly tense without relaxation.

My stiffness index is 2 or higher.

I have stiffness in my limbs and trunk that makes bending hard.

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 week

Treatment

Participants receive KYV-101 CAR T cell therapy

1 day

Follow-up

Participants are monitored for safety, pharmacokinetics, immunogenicity, and efficacy of KYV-101

12 months

Treatment Details

Interventions

• Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

Trial Overview The study tests a new treatment using Anti-CD19 Chimeric Antigen Receptor T Cell (CAR T) Therapy following a standard lymphodepletion regimen. It's designed for those whose Stiff Person Syndrome hasn't responded to usual treatments.

Participant Groups

Group I: KYV-101 CAR-T cells with lymphodepletion conditioning Experimental Treatment 1 Intervention

Dosing with KYV-101 CAR T cells

Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Axicabtagene ciloleucel (Yescarta) for:

• Relapsed or refractory large B-cell lymphoma
• Relapsed or refractory follicular lymphoma

Approved in United States as Tisagenlecleucel (Kymriah) for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia
• Relapsed or refractory diffuse large B-cell lymphoma

Approved in United States as Lisocabtagene maraleucel (Breyanzi) for:

• Relapsed or refractory large B-cell lymphoma

Approved in European Union as Axicabtagene ciloleucel (Yescarta) for:

• Relapsed or refractory diffuse large B-cell lymphoma
• Relapsed or refractory follicular lymphoma

Approved in European Union as Tisagenlecleucel (Kymriah) for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia
• Relapsed or refractory diffuse large B-cell lymphoma

Approved in European Union as Lisocabtagene maraleucel (Breyanzi) for:

• Relapsed or refractory large B-cell lymphoma

Who Is Running the Clinical Trial?

Kyverna Therapeutics

Lead Sponsor

Trials

11

Recruited

320+

Findings from Research

CD19-directed CAR T-cell therapy has shown promising results in treating relapsed/refractory B-cell non-Hodgkin lymphoma, with 30-40% of patients achieving durable responses in pivotal phase I/II trials, leading to FDA and EMA approvals for specific therapies.

Despite its effectiveness, the therapy is associated with significant toxicities, such as cytokine release syndrome and neurotoxicity, which can limit its use and present challenges in patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-directed CAR T-cell therapy in B-cell NHL. Kersten, MJ., Spanjaart, AM., Thieblemont, C.[2021]

CART19 therapy, which targets CD19, has shown significant success in treating relapsed/refractory B cell acute lymphoblastic leukemia (ALL) in patients aged 25 and younger, making it a standard treatment for this age group.

For older adults, CART19 therapy is more complex and typically only available through clinical trials, requiring careful evaluation of treatment goals, potential for stem cell transplants, and the specific risks and benefits of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T in adult ALL: When and for whom? Connor, MP., Frey, NV.[2022]

CAR T-cell therapy is an innovative treatment for difficult-to-treat blood cancers, but there is limited research on the rehabilitation needs of patients undergoing this therapy.

Patients receiving CAR T-cell therapy often experience cognitive impairments, muscle weakness, and fatigue, suggesting that tailored rehabilitation programs could improve their quality of life and functional outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rehabilitation Needs for Patients Undergoing CAR T-Cell Therapy. Obaisi, O., Fontillas, RC., Patel, K., et al.[2022]

CAR.λ T cells effectively target and kill Igλ+ lymphoma cells and chronic lymphocytic leukemia (CLL) cells, showing similar antitumor activity to the established CAR.CD19 T cells in both laboratory and animal models.

Importantly, CAR.λ and CAR.κ T cells selectively deplete only the corresponding light chain-expressing normal B cells, preserving the other type, which suggests a safer approach with minimal impact on the immune system's ability to produce antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. Ranganathan, R., Shou, P., Ahn, S., et al.[2022]

CD19-targeted CAR T cell therapy has shown remarkable efficacy, achieving complete remission in 70-90% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL), highlighting its potential as a powerful treatment for B cell malignancies.

The ongoing phase I study using a non-viral gene transfer method (piggyBac-transposon system) for CD19 CAR T cell therapy in pediatric and young adult patients indicates a promising direction for expanding treatment options in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. Nakazawa, Y.[2017]

Chimeric antigen receptor-modified T cells targeting CD19 showed significant clinical activity in two children with relapsed acute lymphoblastic leukemia (ALL), leading to complete remission in one patient for 11 months after treatment.

While the treatment was effective, both patients experienced severe adverse events, including cytokine-release syndrome and B-cell aplasia, highlighting the need for careful monitoring and potential additional targeting strategies due to the emergence of CD19-negative tumor cells in one patient.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. Grupp, SA., Kalos, M., Barrett, D., et al.[2023]

Tocilizumab is the only interleukin inhibitor currently approved for treating cytokine release syndrome (CRS) caused by CAR-T therapy, demonstrating both efficacy and safety in this context.

Other interleukin inhibitors like siltuximab and anakinra may be beneficial when used alongside tocilizumab to further reduce the risk of severe CRS and neurotoxicity, suggesting potential for improved management of CAR-T therapy side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin Inhibitors in Cytokine Release Syndrome and Neurotoxicity Secondary to CAR-T Therapy. Ferreros, P., Trapero, I.[2022]

CAR T-cell therapy can lead to significant acute toxicities, particularly cytokine release syndrome (CRS) and neurotoxicity, which can result in serious complications and affect ongoing cancer treatment.

Emergency physicians need to be well-informed about these potential toxicities to provide prompt diagnosis and management, which may include supportive care and medications like tocilizumab or corticosteroids for severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Chimeric Antigen Receptor (CAR) T-Cell Toxicities: A Review and Guideline for Emergency Providers. Gupta, R., Roach, C., Hryniewicki, AT., et al.[2021]

References

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

CD19-directed CAR T-cell therapy in B-cell NHL. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

CAR T in adult ALL: When and for whom? [2022]

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

Rehabilitation Needs for Patients Undergoing CAR T-Cell Therapy. [2022]

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

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. [2017]

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

Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Interleukin Inhibitors in Cytokine Release Syndrome and Neurotoxicity Secondary to CAR-T Therapy. [2022]

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

Management of Chimeric Antigen Receptor (CAR) T-Cell Toxicities: A Review and Guideline for Emergency Providers. [2021]