RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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;

Official Title

Phase 1B, Open-Label Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Adult Patients With Treatment Refractory Dermatomyositis

Quick Facts

Study Start:2024-08-02

Study Completion:2039-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06298019

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:25 Years to 72 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Diagnosis of probable or definite (\>55%) IIM and subgroup classification as dermatomyositis according to the 2017 EULAR/ACR classification criteria for idiopathic inflammatory myopathies. 2. 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. * 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. 2.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.	1. Evidence of any of the following: * Severe muscle damage as per one of the following criteria: 1. Myositis Global Damage Index (MDI) ≥5. 2. Severe proximal muscle atrophy of upper or lower extremity on MRI. 3. Severe proximal muscle atrophy of upper or lower extremity on clinical examination. 4. Wheelchair-bound at home. 5. MMT-8 of ≤80. * MDA5-positive rapidly progressing interstitial lung disease (subjects with stable ILD not requiring supplemental oxygen are eligible). * Findings of muscular inflammation or myopathy other than the indication, such as polymyositis (PM), immune mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM), cancer-associated myositis (myositis diagnosed within 2 years of cancer), drug-induced myopathy, amyloid myopathy, muscular dystrophy, metabolic myopathies, or myositis in the context of significant overlap with another systemic autoimmune rheumatologic disease (overlap myositis), except with Sjogren's syndrome. * Generalized, severe musculoskeletal or neuro-muscular conditions other than DM that prevent a sufficient assessment of the patient by the investigator. 2. 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.

Inclusion Criteria

Exclusion Criteria

1. Diagnosis of probable or definite (\>55%) IIM and subgroup classification as dermatomyositis according to the 2017 EULAR/ACR classification criteria for idiopathic inflammatory myopathies.
2. 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.
* 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.
2.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.

1. Evidence of any of the following:
* Severe muscle damage as per one of the following criteria:
1. Myositis Global Damage Index (MDI) ≥5.
2. Severe proximal muscle atrophy of upper or lower extremity on MRI.
3. Severe proximal muscle atrophy of upper or lower extremity on clinical examination.
4. Wheelchair-bound at home.
5. MMT-8 of ≤80.
* MDA5-positive rapidly progressing interstitial lung disease (subjects with stable ILD not requiring supplemental oxygen are eligible).
* Findings of muscular inflammation or myopathy other than the indication, such as polymyositis (PM), immune mediated necrotizing myopathy (IMNM), inclusion body myositis (IBM), cancer-associated myositis (myositis diagnosed within 2 years of cancer), drug-induced myopathy, amyloid myopathy, muscular dystrophy, metabolic myopathies, or myositis in the context of significant overlap with another systemic autoimmune rheumatologic disease (overlap myositis), except with Sjogren's syndrome.
* Generalized, severe musculoskeletal or neuro-muscular conditions other than DM that prevent a sufficient assessment of the patient by the investigator.
2. 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.

Contacts and Locations

Study Contact

Lori Panu

CONTACT

650-724-1703

lpanu@stanford.edu

Principal Investigator

David Fiorentino, MD, PhD

PRINCIPAL_INVESTIGATOR

Stanford University

Lorinda Chung, MD

PRINCIPAL_INVESTIGATOR

Stanford University

Everett Meyer, MD

PRINCIPAL_INVESTIGATOR

Stanford University

Study Locations (Sites)

Stanford University

Palo Alto, California, 94304-5755

United States

Stanford University

Stanford, California, 94305

United States

Collaborators and Investigators

Sponsor: Stanford University

David Fiorentino, MD, PhD, PRINCIPAL_INVESTIGATOR, Stanford University
Lorinda Chung, MD, PRINCIPAL_INVESTIGATOR, Stanford University
Everett Meyer, MD, PRINCIPAL_INVESTIGATOR, Stanford University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-08-02

Study Completion Date2039-04

Study Record Updates

Study Start Date2024-08-02

Study Completion Date2039-04

Terms related to this study

Keywords Provided by Researchers

CAR T
CD19
KYV-101

Additional Relevant MeSH Terms

Dermatomyositis