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

NCT06138132 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 70408
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Sclerosis; Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive

Keywords

KYV-101; autoimmune disease; anti-CD19 CAR-T therapy; cellular therapy

Outcome Measures

Primary Outcomes (1)

• Frequency of dose limiting toxicities at each dose level

  Up to 12 months

Secondary Outcomes (6)

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

  Up to 12 months

• To characterize the pharmacokinetics (PK)

  Up to 12 months

• To characterize the pharmacodynamics (PD)

  Up to 12 months

• To evaluate clinical response

  Up to 12 months

• To evaluate clinical response

  6 months

Study Arms (1)

KYV-101 CAR-T cells with lymphodepletion conditioning

EXPERIMENTAL

Dosing with KYV-101 CAR T cells

Biological: KYV-101 anti-CD19 CAR-T cell therapy; Drug: Standard lymphodepletion regimen

Interventions

KYV-101 anti-CD19 CAR-T cell therapy BIOLOGICAL

KYV-101 anti-CD19 CAR-T cell therapy

KYV-101 CAR-T cells with lymphodepletion conditioning

Standard lymphodepletion regimen DRUG

Standard lymphodepletion regimen

Also known as: Bendamustine

KYV-101 CAR-T cells with lymphodepletion conditioning

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• Stanford University: lead
• Kyverna Therapeutics: collaborator

Study Sites (1)

Stanford Multiple Sclerosis Center

Palo Alto, California, 94304, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 31959992 BACKGROUND

• 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.

  PMID: 21555250 BACKGROUND

• 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.

  PMID: 36109639 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Autoimmune Diseases

Interventions

Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey Dunn, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Multiple Sclerosis and Neuroimmunology Study Team

CONTACT

650-387-5907; neuroimmunologyresearch@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lily Sarafan Director of Neuroimmunology and Professor of Clinical Neurology

Study Record Dates

• First Submitted: November 13, 2023
• First Posted: November 18, 2023
• Study Start: April 10, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)