DermatomyositisPhase 1NCT06298019
Study of KYV-101 Anti-CD19 CAR T Therapy in Adult Dermatomyositis
A Phase 1 study testing KYV-101 in people with Dermatomyositis, run by Stanford University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 72 years
- Conditions the study is for
- Dermatomyositis
- What is being tested?
- KYV-101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Aug 2024to Apr 2039
- 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 25 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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.
- Female sterilization (bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure (provided that occlusion has been confirmed).
- Sexual abstinence, defined as completely and persistently refraining from all heterosexual intercourse (including during the entire period of risk associated with the study treatments) may obviate the need for contraception ONLY if this is the preferred and usual lifestyle of the subject.
- Male subjects, if not surgically sterilized, must agree to use highly effective method of contraception and not donate sperm from the time of signing the ICF until 1 year after the KYV-101 infusion.
- For females: a negative pregnancy test at screening and prior to lymphodepletion chemotherapy.
- Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a KYV-101 infusion.
Who cannot join
- 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.
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- 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.
- History of stroke, seizure, dementia, Parkinson's disease, coordination movement disorder, cerebellar diseases, psychosis, paresis, aphasia, and any other neurologic disorder investigator considers would increase the risk for the subject.
- Impaired cardiac function or clinically significant cardiac disease including:
- Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to apheresis.
- New York Heart Association (NYHA) stage III or IV congestive heart failure.
- History of clinically significant cardiac arrhythmia (eg, ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block.
- History of severe nonischaemic cardiomyopathy.
- Left ventricular ejection fraction (LVEF) <45% as assessed by echocardiogram (ECHO)
- Previous or concurrent malignancy with the following exceptions:
- Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to screening).
- In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to screening.
- A primary malignancy which has been completely resected, or treated, and is in complete remission for at least 5 years prior to screening.
- Serious and/or uncontrolled medical condition that, in the investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol, such as:
- Active, uncontrolled, viral, bacterial or systemic fungal infection (including human T cell lymphotropic virus [HTLV], human polyomavirus 2 [JC virus], or syphilis); or recent history of repeated infections.
- Requirement of supplemental oxygen to maintain oxygen saturation.
- Clinical evidence of dementia or altered mental status.
- A thromboembolic event within 6 months prior to apheresis.
- Ongoing toxicity from previous therapy that has not resolved to baseline levels or to Grade 1 or less, except for alopecia, fatigue, nausea, and constipation.
- Major surgery within 4 weeks prior to apheresis or planned within 4 weeks after KYV-101 administration. For surgery planned after 4 weeks post KYV-101 administration, discuss with the sponsor.
- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to KYV-101 or its excipients, including dimethyl sulfoxide; or to CYC (or to fludarabine if relevant), or to tocilizumab.
- Pregnant or breastfeeding; or plans to become pregnant or breastfeed, or father a child within 1 year after receiving the KYV-101 infusion.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Stanford University
Palo Alto, California, 94304-5755
Swarna Nandyala, 9258548296, swarnan@stanford.edu
- Recruiting
Stanford University
Stanford, California, 94305
Lori Panu, 6507241703, lpanu@stanford.edu
Swarna Nandyala, swarnan@stanford.edu
About this study
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
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
- Being tested
- KYV-101
- Keywords
- CAR T, CD19, KYV-101
- Medical subject headings
- Dermatomyositis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KYV-101Biological
The investigational product, KYV-101, is an autologous CD19-targeted CAR T-cell immunotherapy.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: KYV-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2024
- Study start2 Aug 2024
- Primary completionApr 2027 (estimated)
- Study completionApr 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DermatomyositisStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Fiorentino, Stanford University
- Investigators
- David Fiorentino, MD, PhD, Principal investigator, Stanford UniversityLorinda Chung, MD, Principal investigator, Stanford UniversityEverett Meyer, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06298019
- Sponsor's protocol ID
- 73464
- Status last verified
- Aug 2024
- First submitted
- 16 Dec 2023
- Last updated
- 21 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06298019
- Acronym / sponsor ID
- 73464
- Conditions
- Dermatomyositis
- Keywords
- CAR T, CD19, KYV-101
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 2 Aug 2024 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2039 (estimated)
- First posted
- 7 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active Intervention with CAR T | Experimental | Biological: KYV-101All participants in the trial will receive an infusion of autologous, genetically modified CAR T cells specific for the CD19 antigen |
Who may qualify
- Ages
- 25 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- 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.
- Patient global VAS≥2 cm.
- Physician's global VAS ≥2 cm.
Key exclusion criteria (45 listed)
- DM-related exclusion criteria
- Evidence of any of the following:
- Subject with any of the following:
- oPAH on right heart catheterization requiring PAH specific treatment.
- •Current gangrene of a digit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KYV-101The investigational product, KYV-101, is an autologous CD19-targeted CAR T-cell immunotherapy. | Biological | Active Intervention with CAR T |
Primary outcome
Number of participants experiencing adverse events
Time frame: 24 weeks
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David Fiorentino, MD, PhD principal investigator
Stanford University
Lorinda Chung, MD principal investigator
Stanford University
Everett Meyer, MD principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KYV-101 in people with Dermatomyositis, run by Stanford University at 2 sites 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 30 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 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Lori Panu (650-724-1703, lpanu@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants experiencing adverse events (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 May 2025.