Study of KYV-101 Anti-CD19 CAR T Therapy in Adult Dermatomyositis

NCT06298019 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 73464
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

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) therapy in adult patients with the autoimmune disease dermatomyositis. This study will utilize a technology that modifies a type of white blood cell called the cytotoxic T lymphocyte-this T cell normally functions in the immune system to kill infected or potentially harmful cells in the body. In CAR T therapy, the patients' white blood cells are harvested and the cytotoxic T cells are isolated and modified such that they are programmed to kill any cell that has a protein structure called "CD19" on its outer surface (membrane). Since the CD19 protein is only present on a type of white blood cell called the B lymphocyte, when these "re-engineered" cytotoxic T lymphocytes are then given back to the patient (by an infusion), these cells will seek out and kill essentially all of the patient's B cells. B cells are an important part of a person's immune system and have many functions, including the production of antibodies. It is thought that, in dermatomyositis and other autoimmune diseases, a tiny subset of these B cells plays a large role in making autoantibodies (antibodies directed against the patient's own tissues) and causing disease. The idea is that the therapy will "wipe out" all/most of the B cells in the patient so that they can make an entirely new set of B cells to recreate a functional immune system without the autoimmune disease. The main questions the study intends to answer are:

• Understanding how well patients tolerate undergoing this therapy in terms of side effects;
• Getting an early idea if this therapy can help certain aspects of the autoimmune disease, including inflammation in the skin, muscles, and lungs;

Conditions

Dermatomyositis

Keywords

CAR T; CD19; KYV-101

Outcome Measures

Primary Outcomes (1)

• Number of participants experiencing adverse events

  This outcome is to characterize the safety and tolerability of administering KYV-101 CAR T cells that meet the established criteria to patients with DM. Participants experiencing adverse events including laboratory abnormalities will be reported.

  24 weeks

Study Arms (1)

Active Intervention with CAR T

EXPERIMENTAL

All participants in the trial will receive an infusion of autologous, genetically modified CAR T cells specific for the CD19 antigen

Biological: KYV-101

Interventions

KYV-101 BIOLOGICAL

The investigational product, KYV-101, is an autologous CD19-targeted CAR T-cell immunotherapy.

Active Intervention with CAR T

Eligibility Criteria

• Age: 25 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of probable or definite (\>55%) IIM and subgroup classification as dermatomyositis according to the 2017 EULAR/ACR classification criteria for idiopathic inflammatory myopathies.
• Age \> 25 years and \< 72 years at time of signing informed consent Refractory disease: subject with previous failure (or intolerance) to glucocorticoids and at least two non-glucocorticoid immunosuppressive therapies (including mycophenolate mofetil or mycophenolic acid, cyclophosphamide, azathioprine, methotrexate, calcineurin inhibitors, tofacitinib or other JAK inhibitors, rituximab, or IVIG) administered for at least 12 weeks within 24 months prior to screening.
• Moderate-to-severe dermatomyositis as per EITHER: muscle weakness, defined as Manual Muscle Testing (MMT-8) score \<142/150; or cutaneous disease as per Cutaneous Dermatomyositis Assessment and Severity Index-activity subscore (CDASI-a)\>=19.
• PLUS at least 2 other abnormal IMACS Core Set Measures (CSMs) from the following:
• Patient global VAS≥2 cm.
• Physician's global VAS ≥2 cm.
• Global extramuscular activity score ≥2 cm.
• Elevation of at least one of the muscle enzymes (CK, AST, ALT, aldolase, LDH) \>1.5 times upper limit of normal.
• HAQ-DI≥0.25.
• For patients enrolling on the MMT-8 criterion, muscle disease must be active, as deemed by one of the following:
• Creatine kinase, aldolase, LDH, AST, or ALT (if deemed due to muscle inflammation by investigator) ≥2×ULN.
• MRI evidence of active myositis within last 3 months.
• EMG evidence of active myositis within last 3 months.
• Subject must be ≥25 and ≦72 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• Evidence of any of the following:
• Severe muscle damage as per one of the following criteria:
• Myositis Global Damage Index (MDI) ≥5.
• Severe proximal muscle atrophy of upper or lower extremity on MRI.
• Severe proximal muscle atrophy of upper or lower extremity on clinical examination.
• Wheelchair-bound at home.
• MMT-8 of ≤80.
• MDA5-positive rapidly progressing interstitial lung disease (subjects with stable ILD not requiring supplemental oxygen are eligible).
• Generalized, severe musculoskeletal or neuro-muscular conditions other than DM that prevent a sufficient assessment of the patient by the investigator.
• Subject with any of the following:
• Patients with ILD associated with any of the following oRequiring O2 therapy and/or FVC ≤45% of predicted or DLCO ≤40% of predicted at screening oEvidence of PH as defined as estimated RVSP or ≥45 mmHg or right atrial or ventricular enlargement or dilatation, unless subsequent RHC shows no PH.
• oPAH on right heart catheterization requiring PAH specific treatment.
• Current gangrene of a digit
• Prior treatment with cellular immunotherapy (eg, CAR T) or gene therapy product directed at any target.
• History of allogeneic or autologous stem cell transplant.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (2)

Stanford University

Palo Alto, California, 94304-5755, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Dermatomyositis

Condition Hierarchy (Ancestors)

Polymyositis; Myositis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• David Fiorentino, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Lorinda Chung, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Everett Meyer, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lori Panu

CONTACT

650-724-1703; lpanu@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: Professor in Dermatology

Model Details: Patients will be enrolled in a sequential manner with respect to the aggressiveness of the conditioning regimen used prior to receiving the CAR T infusion therapy. The first 3 patients will undergo standard conditioning--daily cyclophosphamide (IV, 300 mg/m2) and fludarabine (30 mg/m2) x 3 days. If this regimen is found to allow sufficient engraftment of the CAR T cells, participants will be enrolled in sequential groups (of 3-5) representing milder doses or alternative medications that overall represent gentler cytoreduction, which advancement to each sequential group contingent upon satisfactory number and function of infused CAR T cells.

Study Record Dates

• First Submitted: December 16, 2023
• First Posted: March 7, 2024
• Study Start: August 2, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2039
• Last Updated: May 21, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)