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

Recruiting now · Phase 1

Conditions studied: Dermatomyositis

In brief

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;

Key facts

Study ID

NCT06298019

Run by

Stanford University

People needed

21

Starts

2024-08-02

Expected to finish

2039-04-01

Last updated by the study team

2025-05-21

Who can join

Age: 25 and older, up to 72. Sex: any. Healthy volunteers: not accepted.

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.
• Other inclusion criteria: Subject must sign a written ICF prior to any screening procedures.
• Subject must be ≥25 and ≦72 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function as per table below. Haematology Haemoglobin: ≥10.0 g/dl (without prior red blood cell transfusion within 7 days before the laboratory test)a Platelets: ≥100,000/ μL (without transfusion support within 7 days before the laboratory test).
• Absolute Lymphocyte Count (ALC):≥700/μL Absolute Neutrophil Count (ANC) 1,500/μL (prior growth factor support is permitted but must be without support in the 7 days prior to the laboratory test) Hepatic AST and ALT: ≤2.5×upper limit of normal (ULN) unless deemed by the investigator to be secondary to DM.
• Total bilirubin ≤1.5×ULN; except in subjects with congenital bilirubinaemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required) Renal Creatinine clearance Calculated creatinine clearance ≥45 mL/min/1.73 m2 (measured by Cockcroft-Gault equation) Pulmonary Grade≤1 dyspnoea Oxygen saturation measured by pulse oximetry ≥92% on room air a .For subjects who meet the inclusion criteria at screening, transfusion of red blood cells is permitted after screening as needed to maintain a haemoglobin level ≥8.0 g/dL.
• Must be up to date on all recommended vaccinations, including against COVID-19/ SARS CoV-2, per Centers for Disease Control and Prevention or institutional guidelines for immune-compromised individuals.
• Women of childbearing potential must have a negative pregnancy test at screening using a highly sensitive serum pregnancy test (β-human chorionic gonadotropin [β-hCG]). Women of childbearing potential are defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months.
• Female subjects of childbearing potential who have a fertile male sexual partner must agree to use a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) from the time of signing the ICF until 1 year after the KYV-101 infusion. Examples of highly effective method of contraception include:
• Established use of hormonal methods of contraception associated with inhibition of ovulation (eg, oral, inserted, injected, implanted, transdermal), provided the subject or male subject's female partner plans to remain on the same treatment throughout the entire study and has been using that hormonal contraceptive for an adequate period of time to ensure effectiveness.
• Correctly placed copper containing- intrauterine device or intrauterine hormone-replacing system.
• Male sterilization with absence of sperm in the post-vasectomy ejaculate.

You may not qualify if…

• DM-related exclusion criteria
• 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).
• 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.
• 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
• Other exclusion criteria:
• Prior treatment with cellular immunotherapy (eg, CAR T) or gene therapy product directed at any target.
• History of allogeneic or autologous stem cell transplant.
• Systemic autoimmune disease, other than DM, requiring systemic immunosuppressive therapies
• Plan to receive live, attenuated vaccine after signing ICF (inactive vaccines, like the flu vaccine, are allowed). Unable to washout or interrupt autoimmune disease therapy prior to apheresis as specified in Table .
• Positive hepatitis B surface antigen (HBsAg) and hepatitis C serology confirmed by polymerase chain reaction (PCR) (except hepatitis C cured with pharmacotherapy); subjects who are HBsAg negative and hepatitis B core antibody (HBc) positive with no detectable DNA will be allowed into the study but will require regular monitoring of hepatitis B virus (HBV) DNA.
• Positive serology for human immunodeficiency virus (HIV).
• Positive screening test for SARS-Cov-2.
• Primary immunodeficiency.
• History of splenectomy.

Where it is running

• Stanford University — Palo Alto, California, United States (enrolling)
• Stanford University — Stanford, California, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.