CAR T-cell Therapy for Multiple Sclerosis
Recruiting in Palo Alto (17 mi)
JD
Overseen byJeffrey Dunn, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: Stanford University
Must not be taking: Anticoagulants, Antiplatelets, Anti-CD20
Disqualifiers: HIV, Hepatitis B, Hepatitis C, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis
Do I need to stop my current medications for the trial?
The trial requires a washout period for certain medications: a 30-day washout for glatiramer acetate, interferon-beta, and fumarates, and a 60-day washout for sphingosine-i-phosphate modulators and natalizumab. If you are on these medications, you will need to stop them before participating.
What safety data exists for CAR T-cell therapy in humans?
CAR T-cell therapy has been associated with serious side effects, including cytokine release syndrome (a severe immune reaction) and neurological issues. Cardiovascular problems like arrhythmias (irregular heartbeats) and heart failure have also been reported, with a higher risk of these events leading to increased mortality.12345
How is the treatment KYV-101 different from other treatments for multiple sclerosis?
Research Team
JD
Jeffrey Dunn, MD
Principal Investigator
Stanford University
Eligibility Criteria
This trial is for adults aged 18-55 with progressive forms of Multiple Sclerosis, as per the McDonald and Lublin criteria. Participants must have certain antibody levels, normal organ function, no recent investigational drugs or specific treatments, and agree to contraception if applicable.Inclusion Criteria
You have been diagnosed with multiple sclerosis using the 2017 McDonald Criteria.
My kidney, liver, lung, and heart functions are all within normal ranges.
You need to be tested to make sure you don't have certain infections or diseases.
See 9 more
Exclusion Criteria
I have a heart valve condition.
My kidneys do not work well.
I have a history of NMOSD or MOGAD.
See 9 more
Trial 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 cells
1 day
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and clinical response
12 months
Treatment Details
Interventions
- KYV-101 (CAR T-cell Therapy)
Trial OverviewThe study tests KYV-101 anti-CD19 CAR-T cell therapy following a standard lymphodepletion regimen in patients with non-relapsing and progressive MS. It aims to evaluate the safety and effectiveness of this innovative treatment approach.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: KYV-101 CAR-T cells with lymphodepletion conditioningExperimental Treatment2 Interventions
Dosing with KYV-101 CAR T cells
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford Multiple Sclerosis CenterPalo Alto, CA
Loading ...
Who Is Running the Clinical Trial?
Stanford University
Lead Sponsor
Trials
2527
Patients Recruited
17,430,000+
Kyverna Therapeutics
Industry Sponsor
Trials
11
Patients Recruited
320+
Findings from Research
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project.Foster, M., Negash, Y., Eberhardt, L., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Associated Toxicities: Assessment and Management Related to CAR T-Cell Therapy.Anderson, K., Latchford, T.[2020]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
[Management of adverse events of CAR-T therapy].Arai, Y.[2023]
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]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies.Saiz, LC., Leache, L., Gutiérrez-Valencia, M., et al.[2023]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Engineered regulatory T cells expressing myelin-specific chimeric antigen receptors suppress EAE progression.De Paula Pohl, A., Schmidt, A., Zhang, AH., et al.[2022]
A new clinical platform successfully generates CMV-CD19CAR T cells from healthy donors, achieving a high enrichment of CMV-specific T cells and a transduction efficiency of 27%, which is crucial for effective cancer treatment.
These CMV-CD19CAR T cells showed strong anti-tumor activity and maintained memory characteristics, indicating their potential for improved persistence and efficacy in treating B cell malignancies, with plans for a clinical trial in patients with non-Hodgkin's lymphoma.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Large-scale manufacturing and characterization of CMV-CD19CAR T cells.Wang, X., Urak, R., Walter, M., et al.[2022]
The study developed a method to enhance the effectiveness of CD4+CD25+ regulatory T-cells by genetically modifying them to specifically target and suppress harmful T lymphocytes, showing significant potential for treating autoimmune diseases.
In an experimental model of allergic encephalomyelitis, these modified T-cells not only prevented disease onset but also achieved complete remission and reduced mortality from over 50% to 0%, demonstrating their powerful therapeutic efficacy.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes.Mekala, DJ., Geiger, TL.[2021]
In a study of 45 patients with active CNS lymphoma receiving CAR T-cell therapy, 68.9% showed a CNS response, with 40% achieving a complete response lasting an average of 11.4 months, indicating the therapy's efficacy in this challenging population.
While CAR T-cell therapy demonstrated a favorable safety profile, mild to severe neurotoxicity (ICANS) occurred in 42.2% and 15.6% of transfusions, respectively, with higher risks associated with secondary CNS lymphoma and certain pre-treatment factors.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells.Karschnia, P., Arrillaga-Romany, IC., Eichler, A., et al.[2023]
CAR T-cell therapy is a powerful immunotherapy that not only shows promise in treating various cancers but can also be adapted to target autoimmune diseases and infections like HIV.
The therapy utilizes engineered T cells that can recognize a wider range of targets compared to natural T cells, enhancing its potential effectiveness in diverse medical applications.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Application of CAR-T cell technology in autoimmune diseases and human immunodeficiency virus infection treatment.Adabi, N., Pordel, S., Rezaee, MA., et al.[2023]
References
Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. [2022]
Associated Toxicities: Assessment and Management Related to CAR T-Cell Therapy. [2020]
[Management of adverse events of CAR-T therapy]. [2023]
Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis. [2021]
Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies. [2023]
Engineered regulatory T cells expressing myelin-specific chimeric antigen receptors suppress EAE progression. [2022]
Large-scale manufacturing and characterization of CMV-CD19CAR T cells. [2022]
Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes. [2021]
Neurotoxicity and management of primary and secondary central nervous system lymphoma after adoptive immunotherapy with CD19-directed chimeric antigen receptor T-cells. [2023]
Application of CAR-T cell technology in autoimmune diseases and human immunodeficiency virus infection treatment. [2023]