Systemic Lupus ErythematosusPhase 1SLENCT06691152
Efficacy and Safety of CD19 UCAR T Cells in Refractory Systemic Lupus Erythematosus
A Phase 1 study testing CD19 Universal CAR-T cells in people with Systemic Lupus Erythematosus, run by The Children's Hospital of Zhejiang University School of Medicine at 1 site in China.
Trial summary
This is an investigator-initiated trial to evaluate the safety and efficacy of CD19 Universal CAR-T cells in the treatment of refractory systemic lupus erythematosus. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- CD19 Universal CAR-T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 30 Oct 2024to 30 Sep 2027
- 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 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age:≥5 years old;
- Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria；Still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod ), hydroxychloroquine and at least 2 of the following treatments(cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab); or Intolerant to standard treatments;
- SLEDAI 2K score≥8 points;
- The functions of important organs are basically normal:
- Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2； Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN; Lung function: No serious lung lesions, SpO2≥92%;
- Met the standards of leukapheresis or intravenous blood collection, No contraindication for cell collection;
- Negative pregnancy test for female Subjects of childbearing age, agree to take effective contraceptive measures the first year after CAR-T infusion;
- Participants or their guardians agrees to participate in the clinical trial and sign the informed consent form which indicating that he/she understands the purpose and procedure of the clinical trial and is willing to participate in the study.
Who cannot join
- Received CAR T cell therapy previously;
- Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
- Active tuberculosis at the time of screening;
- Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
- Suffer from other diseases that require long-term use of glucocorticoid or high-dose of immunosuppressive agents;
- Uncontrollable infection, or active infection that requires systemic treatment within 1 week prior to screening；
Show all 13Show fewer
- History of organ transplantation or hematopoietic stem cell transplantation, or ≥Grade 2 GVHD within 2 weeks prior to screening；
- Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer greater than the normal reference value range; Or hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA titer greater than the normal reference value range; Or positive for human immunodeficiency virus (HIV) antibodies; Or syphilis test positive; Or cytomegalovirus (CMV) DNA test positive;
- Received live vaccine within 4 weeks before screening;
- Tested positive in Blood pregnancy test；
- Previous or concurrent malignancy；
- Patients who participated in other clinical study within 3 months prior to enrollment;
- Any other conditions that the investigators deem it unsuitable for the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Children's Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310052
Jianhua Mao, MD, +86-571-86670076, maojh88@zju.edu.cn
Xue He, MD, +8615088688407, 6511009@zju.edu.cn
About this study
Official title: Efficacy and Safety Study of CD19 Universal CAR T Cells in Refractory Systemic Lupus Erythematosus
This is an investigator-initiated trial to evaluate the safety and efficacy of CD19 Universal CAR-T cells in the treatment of refractory systemic lupus erythematosus.
Read the detailed description
Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can lead to extensive damage in multiple organs and systems, ultimately resulting in disability and even death. Children with SLE are particularly at risk of organ damage, especially to the kidneys, and tend to have a more severe and protracted course of the disease compared to adults. Since 2019, CAR T-cell therapy has been successfully applied to autoimmune diseases. Clinical studies have demonstrated that targeted auto-CD19 CAR T-cells hold significant therapeutic potential for SLE. These cells effectively slow down the pathological progression of SLE and can also effectively treat severe cases. However, there are many limitations to the wide application of autologous CAR T-cells, autologous CAR T-cells are "personalized" products, which take a long time to produce, and their quality is affected by the patient's own physique, which is not conducive to scale and standardization. Besides, due to the personalized and complex preparation process of autologous CAR-T cell products, the costs are quite high which limits the promotion of use in the population. Compared with autologous CAR-T cell product, universal CAR-T cell products derived from healthy donors, it is not affected by the quantity and quality of the patient's T cells, leading to a high success rate in preparation. A single batch can meet the needs of hundreds of people, offering absolute advantages in time and cost. Compared to traditional autologous CAR-T cells, allogeneic universal CAR T-cells can greatly expand the accessibility of the product to patients, benefiting more patients. The purpose of this study is to assess the safety and efficacy of the CD19 universal CAR-T cells in the treatment of refractory SLE.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- CD19 Universal CAR-T cells
- Keywords
- Systemic Lupus Erythematosus, CAR T-Cells, Pediatrics
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19 Universal CAR-T cellsBiological
Three dose groups (1×10^7/kg, 3×10^7/kg, 6×10^7/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose.
| Study group | Role | What they receive |
|---|---|---|
| CAR T cell treatment group | Experimental | This trial was designed as an open, single-arm, multicenter, dose-increasing trial, three dose groups (1×10^7/kg, 3×10^7/kg, 6×10^7/kg) are set up, starting from the low dose group to explore the safe and effective dose. Receives: Biological: CD19 Universal CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events related to CD19 universal CAR-T cells
Incidence and severity of AEs associated with CD19 universal CAR-T cells as assessed by CTCAE v5.0
Measured: 3 months
Secondary outcomes (4)
Proportion of patients achieving DORIS remission after CD19 universal CAR-T infusion
6M DORIS response rate
Measured: 6 months
Proportion of patients achieving low disease activity status (LLDAS) after CD19 universal CAR-T infusion
LLDAS maintenance rate at 3M and 6M
Measured: 3 months and 6 months
Proportion of patients achieving SRI-4 remission after CD19 universal CAR-T infusion
SRI-4 response rate at 3M and 6M
Measured: 3 months and 6 months
Cellular kinetics
CAR transgene levels by quantitative polymerase chain reaction (qPCR) in peripheral blood.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2024
- Study start30 Oct 2024
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by The Children's Hospital of Zhejiang University School of MedicineThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mao Jianhua, The Children's Hospital of Zhejiang University School of Medicine
- Investigators
- Jianhua Mao, Principal investigator, The Children's Hospital of Zhejiang University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06691152
- Sponsor's protocol ID
- PBC078
- Acronym
- SLE
- Status last verified
- Nov 2024
- First submitted
- 11 Nov 2024
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.
PubMed 34347960Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
PubMed 38381673Charras A, Smith E, Hedrich CM. Systemic Lupus Erythematosus in Children and Young People. Curr Rheumatol Rep. 2021 Feb 10;23(3):20. doi: 10.1007/s11926-021-00985-0.
PubMed 33569643Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.
PubMed 28925994
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety Study of CD19 Universal CAR T Cells in Refractory Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT06691152
- Acronym / sponsor ID
- SLE / PBC078
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Systemic Lupus Erythematosus, CAR T-Cells, Pediatrics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- The Children's Hospital of Zhejiang University School of MedicineUniversity, hospital or other
- Study start
- 30 Oct 2024 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 15 Nov 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.
This is an investigator-initiated trial to evaluate the safety and efficacy of CD19 Universal CAR-T cells in the treatment of refractory systemic lupus erythematosus.
Detailed description
Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can lead to extensive damage in multiple organs and systems, ultimately resulting in disability and even death. Children with SLE are particularly at risk of organ damage, especially to the kidneys, and tend to have a more severe and protracted course of the disease compared to adults. Since 2019, CAR T-cell therapy has been successfully applied to autoimmune diseases. Clinical studies have demonstrated that targeted auto-CD19 CAR T-cells hold significant therapeutic potential for SLE. These cells effectively slow down the pathological progression of SLE and can also effectively treat severe cases. However, there are many limitations to the wide application of autologous CAR T-cells, autologous CAR T-cells are "personalized" products, which take a long time to produce, and their quality is affected by the patient's own physique, which is not conducive to scale and standardization. Besides, due to the personalized and complex preparation process of autologous CAR-T cell products, the costs are quite high which limits the promotion of use in the population. Compared with autologous CAR-T cell product, universal CAR-T cell products derived from healthy donors, it is not affected by the quantity and quality of the patient's T cells, leading to a high success rate in preparation. A single batch can meet the needs of hundreds of people, offering absolute advantages in time and cost. Compared to traditional autologous CAR-T cells, allogeneic universal CAR T-cells can greatly expand the accessibility of the product to patients, benefiting more patients. The purpose of this study is to assess the safety and efficacy of the CD19 universal CAR-T cells in the treatment of refractory SLE.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR T cell treatment group | Experimental | Biological: CD19 Universal CAR-T cellsThis trial was designed as an open, single-arm, multicenter, dose-increasing trial, three dose groups (1×10^7/kg, 3×10^7/kg, 6×10^7/kg) are set up, starting from the low dose group to explore the safe and effective dose. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Age:≥5 years old;
- Diagnosed with SLE according to the 2019 EULAR/ACR SLE classification criteria；Still in moderate to severe disease activity despite ≥3M of high dose glucocorticoids(prednisone≥1mg/kg/d or other equivalent amount of other steriod ), hydroxychloroquine and at least 2 of the following treatments(cyclophosphamide, MMF, azathioprine, methotrexate, cyclosporin, tacrolimus, sirolimus, leflunomide, telitacicept, Beliumab, and rituximab); or Intolerant to standard treatments;
- SLEDAI 2K score≥8 points;
- The functions of important organs are basically normal:
- Cardiac function: Left ventricular ejection fraction (LVEF) ≥55% with no obvious abnormality in electrocardiogram; Renal function: eGFR≥30ML/min/1.73m2； Liver function: Asparagus cochinchinensis transase (AST) and Alanine Aminotransferase (ALT)≤3.0 ULN, Total Bilirubin (TBIL) in serum ≤2.0×ULN; Lung function: No serious lung lesions, SpO2≥92%;
Key exclusion criteria (13 listed)
- Received CAR T cell therapy previously;
- Central nervous system (CNS) disease: CNS neurolupus requires intervention within 60 days);
- Active tuberculosis at the time of screening;
- Have a history of congenital heart disease or acute myocardial infarction within 6 months prior to screening; Or severe arrhythmias (including multisource frequent supraventricular tachycardia, ventricular tachycardia, etc.); Or combined with moderate to massive pericardial effusion, serious myocarditis, etc; Or patients with unstable vital signs who need hypertensive drugs；
- Suffer from other diseases that require long-term use of glucocorticoid or high-dose of immunosuppressive agents;
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 |
|---|---|---|
| CD19 Universal CAR-T cellsThree dose groups (1×10^7/kg, 3×10^7/kg, 6×10^7/kg) were set up, starting from the low dose group climbing to explore the safe and effective dose. | Biological | CAR T cell treatment group |
Primary outcome
Adverse events related to CD19 universal CAR-T cells
Time frame: 3 months
Incidence and severity of AEs associated with CD19 universal CAR-T cells as assessed by CTCAE v5.0
4 secondary outcomes
Proportion of patients achieving DORIS remission after CD19 universal CAR-T infusion
Time frame: 6 months
Proportion of patients achieving low disease activity status (LLDAS) after CD19 universal CAR-T infusion
Time frame: 3 months and 6 months
Proportion of patients achieving SRI-4 remission after CD19 universal CAR-T infusion
Time frame: 3 months and 6 months
Cellular kinetics
Time frame: 6 months
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 15 Nov 2024.
- Results publication: PubMed 34347960Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.
- Results publication: PubMed 38381673Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
- Results publication: PubMed 33569643Charras A, Smith E, Hedrich CM. Systemic Lupus Erythematosus in Children and Young People. Curr Rheumatol Rep. 2021 Feb 10;23(3):20. doi: 10.1007/s11926-021-00985-0.
- Results publication: PubMed 28925994Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018 Jan;15(1):47-62. doi: 10.1038/nrclinonc.2017.148. Epub 2017 Sep 19.
- 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.
Jianhua Mao principal investigator
The Children's Hospital of Zhejiang University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD19 Universal CAR-T cells in people with Systemic Lupus Erythematosus, run by The Children's Hospital of Zhejiang University School of Medicine at 1 site in China.
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 8 inclusion and 13 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 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 Jianhua Mao, Prof (0571-86670076, maojh88@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events related to CD19 universal CAR-T cells (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06691152, which also lists 4 linked publications.
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 15 Nov 2024.