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Multiple SclerosisPhase 1NCT06138132

A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell ( CAR-T) Therapy in Subjects With Non-relapsing and Progressive Forms of Multiple Sclerosis

A Phase 1 study testing KYV-101 anti-CD19 CAR-T cell therapy and Standard lymphodepletion regimen in people with Multiple Sclerosis and Multiple Sclerosis, Primary Progressive, run by Stanford University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
KYV-101 anti-CD19 CAR-T cell therapy and Standard lymphodepletion regimen
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
10 Apr 2024to Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient is ≥ 18 years old, and ≤65 years of age, at time of screening visit.
  • Diagnosis of MS according to the 2017 McDonald Criteria.
  • Progressive MS by 2014 Lublin MS phenotypic criteria.
  • Presence of varicella-zoster virus (VZV) antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least four weeks prior to treatment.
  • Presence of anti EBV antibodies.
  • Organ and Marrow Function
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  • Absolute neutrophil count (ANC) ≥ 2000/uL.
  • Platelet count ≥ 150,000/uL.
  • Absolute lymphocyte count ≥ 1000/uL.
  • Serum immunoglobulin G (IgG) ≥ 500mg/dL.
  • Hemoglobin ≥ 9 g/dL.
  • Adequate renal, hepatic, pulmonary and cardiac function defined as:
  • Creatinine ≤ 2mg/dL or creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min.
  • Serum alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN).
  • Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome
  • Cardiac ejection fraction ≥ 40%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, and no clinically significant ECG findings.
  • Baseline oxygen saturation > 94% on room air.
  • Testing for
  • Hepatitis B core antibody (HBc Ab)
  • Hepatitis C antibody (HCV Ab)
  • Hepatitis B surface antigen (Hep B surf. AG)
  • HIV 1\&2 Ab
  • Syphilis Screen
  • Human T-cell lymphotropic virus (HTLV) Ab I \& II
  • Nucleic acid test multiplex (NAT MPX) for HIV, HCV, HBV
  • Herpes Simplex Virus 1 \& 2 IgG panel
  • Varicella-Zoster (VZ) IgG
  • Cytomegalovirus (CMV) Total Ab
  • Must be seronegative for HIV-1 RNA polymerase chain reaction (PCR); HIV 1 and HIV 2 Ab (antibody); HTLV-1 and HTLV-2 Ab; PCR+ or negative surface antigen for hepatitis B; negative for the Treponema pallidum antibody Syphilis screen; and negative for HIV-1 and hepatitis C by nucleic acid testing (NAT) within 40 days of apheresis procedures.
  • Females of childbearing potential have a negative serum or urine pregnancy test because of the potentially dangerous/unknown effects on the fetus. Females who have undergone hysterectomy or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
  • Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice highly effective birth control from the time of enrollment on this study and for the entire study period which is 12 months after receiving the CAR T cell infusion.
  • Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.
  • Adequate vital sign criterion with acceptable numerical ranges of:
  • Systolic Blood Pressure (mmHg) ≥ 100 and ≤ 150
  • Diastolic Blood pressure (mmHg) ≥ 60 and ≤ 90
  • To ensure subject safety and stability, any subject who is noted to have a BP > 150/90 mm Hg should be stable on anti-hypertensive medications with repeated BP ≤150/90 for at least one month prior to enrollment in the study
  • Heart Rate ≥ 60 and ≤ 100 bpm
  • Oral Temperature ≤ 37.7 C/afebrile
  • Respiratory rate ≥ 12 and ≤ 20bpm

Who cannot join

  • History of neuromyelitis optica spectrum disorder (NMOSD) or MOG antibody associated disease (MOGAD).
  • Prior treatment with any investigational agent within 3 months, or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not considered investigational.
  • Initiation of any DMT between the completion of apheresis and start of lymphodepletion (LD) chemotherapy. The use of methylprednisolone for bridging therapy between apheresis and start of LD chemotherapy will be allowed.
  • History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis or non-MS progressive neurologic condition affecting ability to perform study assessments.
  • History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
  • History of sickle cell anemia or other hemoglobinopathy.
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  • Coagulation abnormalities defined by: international normalized ratio (INR) > 1.5, prothrombin time (PT) > 14 seconds, partial thromboplastin time (PTT) > 45 seconds to the exclusion criteria. Patients with positive antiphospholipid antibodies, including anti-cardiolipin, or lupus anticoagulant.
  • Presence of fungal, bacterial, viral, or other infection that is not controlled and/ or requiring hospitalization or treatment with IV antimicrobials within 4 weeks of screening. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
  • Psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the Stanford Transplant team caring for this potential patient would place the patient at an unacceptable risk.
  • Presence or history of liver cirrhosis.
  • History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
  • Active infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive) as the immunosuppression contained in this study may pose unacceptable risk. A prior history of hepatitis B or hepatitis C is permitted providing the viral load is undetectable per quantitative PCR and/or nucleic acid testing. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.
  • Central nervous system (CNS) disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease unrelated to MS that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease (uncontrolled congestive heart failure) within 4 months of enrollment. Subjects with stable cardiac disease fulfilling inclusion criteria are allowed.
  • Subjects receiving anticoagulation therapy or subjects with concomitant use of antiplatelet agents.
  • History of Crohn's, rheumatoid arthritis, systemic lupus that required continued systemic immunosuppression/systemic disease modifying agents within the 2 years prior to trial enrollment.
  • A primary immune deficiency disease
  • In the investigator's judgment, the subject is unlikely to complete protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study. This includes contraindications or life-threatening allergies, hypersensitivity, or intolerance to KYV-101 or its excipients, including dimethyl sulfoxide; Bendamustine; or tocilizumab.
  • Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment.
  • Prior treatment with total lymphoid irradiation or mitoxantrone exceeding 36 mg/m2 cumulative dose
  • Prior treatment with autologous hematopoietic stem cell transplantation, or prior history of cellular immunotherapy (eg. CAR T) or gene therapy directed at any target.
  • Prior treatment with anti-CD20+ monoclonal antibody therapy within 9 months of trial initiation. A 30-day washout will be required for prior treatment with glatiramer acetate, interferon-beta, and fumarates. A 60-day washout will be required for sphingosine-i-phosphate modulators and natalizumab. Excluded will be patients who received prior treatment with mitoxantrone regardless of prior cumulative dose.
  • Prior history of solid organ transplantation
  • Impaired cardiac function or clinically significant cardiac disease including:
  • a. Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to apheresis.
  • b. New York Heart Association (NYHA) stage III or IV congestive heart failure.
  • c. History of clinically significant cardiac arrhythmia (eg, ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block.
  • d. History of severe nonischemic cardiomyopathy.
  • e. Left ventricular ejection fraction (LVEF) <45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis).
  • f. Active, current cardiac manifestations of systemic lupus erythematosus (SLE) including pericarditis, pericardial effusion, and myocarditis.
  • Prior history of splenectomy
  • History of moderate or worse than moderate asthma or chronic obstructive pulmonary disease (COPD)
  • Corrected QT interval (QTc) >450msec in males or >470msecs in females
  • Subjects with valvular heart disease (regurgitation, stenosis or atresia
  • Moderate or worse renal impairment using criteria
  • Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m^2).
  • Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m^2).
  • Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73 m^2).
  • Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73 m^2).
  • Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m^2).
  • Stage 5: Kidney failure (GFR < 15 mL/min/1.73 m^2 or dialysis)
  • Previously received Mavenclad, yet drug washout is ≤9 months.
  • History of a seizure disorder even if the seizure disorder is well controlled with anti-epileptics
  • Prior history of treatment with cellular immunotherapy (e.g. CAR T) gene therapy product directed as any target.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Multiple Sclerosis and Neuroimmunology Study Team contact

650-387-5907

neuroimmunologyresearch@stanford.edu

United States1 site, 1 recruiting

  • Stanford Multiple Sclerosis Center

    Palo Alto, California, 94304

    Emma Martinez, BA, 650-387-5907, eam1@stanford.edu

    Jeffrey Dunn, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1, Open-Label, Single Center Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy in Subjects With Non-relapsing and Progressive Forms of Multiple Sclerosis

A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis

Read the detailed description

Multiple Sclerosis (MS) is an immune-mediated neurodegenerative central nervous system disease that can lead to loss of vital neurologic function. The clinical course of MS from person to person is variable. Progressive Multiple Sclerosis (pMS) is marked by a history of neurologic worsening over time; and can occur following a prior history of defined relapses that has evolved to a non-relapsing state (previously termed "secondary progressive MS" (SPMS)) or from disease onset (termed "primary progressive MS" (PPMS)).

There are now more than twenty FDA approved disease modifying therapies (DMTs) for MS in the United States. Most of these treatments have an approved FDA indication for relapsing disease. Several have a labeled indication for active secondary progressive MS, and only one has been FDA approved for primary progressive MS. There are no formally approved treatments for patients with non-relapsing progressive Multiple Sclerosis that is worsening, treatment refractory, and non-active as defined operationally by absence of relapse of magnetic resonance imaging evidence of inflammatory disease within the preceding two years.

B cells play a central and multi-functional role in the immunopathogenesis of MS. B cells present antigen to T cells in stimulating a pro-inflammatory immune cascade, secrete pathogenic cytokines, moderate T cell and myeloid cell functions, form structural B cell meningeal follicles within the human central nervous system, act as reservoirs for Epstein-Barr virus (EBV) infection, and produce pathogenic antibodies upon evolution to plasma cells. CD19-targeted chimeric antigen receptor (CAR) T cells harness the ability of cytotoxic T cells to directly and specifically lyse target cells to effectively deplete B cells in the circulation and in lymphoid and potentially non-lymphoid tissues. KYV-101, a fully human anti-CD19 CAR T-cell therapy, will be investigated in adult subjects with non-relapsing and progressive forms of MS.

Being tested
KYV-101 anti-CD19 CAR-T cell therapy, Standard lymphodepletion regimen
Keywords
KYV-101, autoimmune disease, anti-CD19 CAR-T therapy, cellular therapy
Medical subject headings
Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Autoimmune Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KYV-101 anti-CD19 CAR-T cell therapyBiological

    KYV-101 anti-CD19 CAR-T cell therapy

  • Standard lymphodepletion regimenDrug

    Also called Bendamustine

    Standard lymphodepletion regimen

Study groups in NCT06138132
Study groupRoleWhat they receive
KYV-101 CAR-T cells with lymphodepletion conditioningExperimentalDosing with KYV-101 CAR T cells
Receives: Biological: KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency of dose limiting toxicities at each dose level

    Measured: Up to 12 months

Secondary outcomes (6)

  1. Incidence of adverse events (AEs) including clinical tolerance and laboratory abnormalities

    Clinical tolerance will be assessed with attention to cytokine release syndrome (CRS), Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) and other AE to be graded by CTCAE Version 5.0

    Measured: Up to 12 months

  2. To characterize the pharmacokinetics (PK)

    Levels of KYV-101 CAR-positive T cells in the blood and cerebrospinal fluid from treatment baseline to end of study

    Measured: Up to 12 months

  3. To characterize the pharmacodynamics (PD)

    Levels of B cells in the blood from treatment baseline to end of study

    Measured: Up to 12 months

  4. To evaluate clinical response

    Time from CD19 KYV CAR T cell infusion to a change in disability and walking score, as measured by the Kurtzke Expanded Disability Status Scale (EDSS)

    Measured: Up to 12 months

  5. To evaluate clinical response

    Levels of unique unmatched intrathecal oligoclonal bands from treatment baseline to 6 months following treatment

    Measured: 6 months

  6. To evaluate clinical response

    Whole brain and grey matter volume from treatment baseline to end of study

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2023
  2. Study start10 Apr 2024
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06138132
Sponsor's protocol ID
70408
Status last verified
Mar 2025
First submitted
13 Nov 2023
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Brudno JN, Lam N, Vanasse D, Shen YW, Rose JJ, Rossi J, Xue A, Bot A, Scholler N, Mikkilineni L, Roschewski M, Dean R, Cachau R, Youkharibache P, Patel R, Hansen B, Stroncek DF, Rosenberg SA, Gress RE, Kochenderfer JN. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med. 2020 Feb;26(2):270-280. doi: 10.1038/s41591-019-0737-3. Epub 2020 Jan 20.

    PubMed 31959992

  • Barun B, Bar-Or A. Treatment of multiple sclerosis with anti-CD20 antibodies. Clin Immunol. 2012 Jan;142(1):31-7. doi: 10.1016/j.clim.2011.04.005. Epub 2011 Apr 15.

    PubMed 21555250

  • Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.

    PubMed 36109639

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KYV-101 anti-CD19 CAR-T cell therapy and Standard lymphodepletion regimen in people with Multiple Sclerosis and Multiple Sclerosis, Primary Progressive, run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 39 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Multiple Sclerosis and Neuroimmunology Study Team (650-387-5907, neuroimmunologyresearch@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of dose limiting toxicities at each dose level (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06138132, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2026.

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