Systemic Lupus Erythematosus (SLE)Phase 1NCT03030976
A Study of CD19 Redirected Autologous T Cells for CD19 Positive Systemic Lupus Erythematosus (SLE)
A Phase 1 study testing cyclophosphamide and anti-CD19-CAR-T cells in people with Systemic Lupus Erythematosus (SLE), run by Shanghai GeneChem Co., Ltd. at 1 site in China.
Trial summary
CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Systemic Lupus Erythematosus (SLE)
- What is being tested?
- cyclophosphamide and anti-CD19-CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteChina
- Study dates
- Mar 2017to Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of systemic lupus erythematosus (SLE) patients
- Patients with CD19+ B-cell SLE as confirmed by Flow Cytometry
- Age: 18-69 years old
- Creatinine < 1.5 mg/dl
- cardiac ejection fraction>55%
- hemoglobin>9g/dL
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- Bilirubin <2.0 mg/dl
- Successful test expansion of T-cells
- Adequate venous access for apheresis, and no other contraindications for leukapheresis
- Voluntary informed consent is given
Who cannot join
- Pregnant or lactating women
- Uncontrolled active infection
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- Previously treatment with any gene therapy products
- Feasibility assessment during screening demonstrates<5% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
- Any serious, uncontrolled diseases (including, but not limit to, unstable angina pectoris, congestive heart failure, serious arrhythmia)
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Jiaotong University School of Medicine, Renji Hospital
Shanghai, 200127
Qiang Guo, Doctor, 86-21-63835620, bluedescent@126.com
About this study
Official title: An Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With CD19+ B Cell Systemic Lupus Erythematosus (SLE)
CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of the central nervous system). SLE is a kind of autoimmune diseases which involving multiple systems, organs and with the present of a variety of autoantibodies. In the conventional treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells in the treatment of SLE.
Read the detailed description
This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Being tested
- cyclophosphamide, anti-CD19-CAR-T cells
- Keywords
- CD19, CAR-T, SLE
- 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.
cyclophosphamideDrug
Also called Cy
Patients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d.
anti-CD19-CAR-T cellsDrug
Also called 2nd CAR-T
A 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge \& transmembrane domain sequences. Patients infused with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity to treatment of SLE. The dose is 1E6~1E7 CD19-CAR positive T cells. The cells infusion process may last for 30 min.
| Study group | Role | What they receive |
|---|---|---|
| Reduce B cells | Experimental | Patients receive cyclophosphamide to reduce B cells before CD19-CART infusion. It will also reduce the side effects of cell damage due to antitumor activity. Receives: Drug: cyclophosphamide |
| Treatment of SLE | Experimental | Patients receive anti-CD19-CAR-T cells to treatment of SLE. The purpose of this study is to assess the safety and efficacy of CD19 CAR-T cells in the treatment of SLE. Receives: Drug: anti-CD19-CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of CAR-T cell（i.v.）by number of patients with adverse event
adverse event is evaluated with CTCAE, version 4.0
Measured: 6 weeks
Secondary outcomes (2)
Number of patients with tumor response
summarize tumor response by overall response rates
Measured: 8 weeks
3. Detection of transferred T cells in the circulation using quantitative -PCR
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2017 (estimated)
- Study startMar 2017 (estimated)
- Primary completionJan 2018 (estimated)
- Study completionMar 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Systemic Lupus Erythematosus (SLE)Studies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai GeneChem Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- RenJi Hospital
- Responsible party
- Sponsor
- Investigators
- Qiang Guo, Doctor, Principal investigator, RenJi Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03030976
- Sponsor's protocol ID
- CD19-CART for SLE
- Status last verified
- Jan 2017
- First submitted
- 22 Jan 2017
- Last updated
- 7 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-labeled, Uncontrolled, Single-arm Pilot Study to Evaluate Cellular Immunotherapy Using CD19-targeted Chimeric Antigen Receptor Engineered T Cells in Patients With CD19+ B Cell Systemic Lupus Erythematosus (SLE)
- ClinicalTrials.gov ID
- NCT03030976
- Acronym / sponsor ID
- CD19-CART for SLE
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Keywords
- CD19, CAR-T, SLE
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Shanghai GeneChem Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- RenJi Hospital
- Study start
- Mar 2017 (estimated)
- Primary completion
- Jan 2018 (estimated)
- Study completion
- Mar 2018 (estimated)
- First posted
- 25 Jan 2017 (estimated)
- 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.
CAR-T therapy was therefore proposed and has been recently used for cancer treatment. It has been hailed for its promising remission rates after early stage clinical trials for acute lymphoblastic leukemia. However, CAR-T therapy is seldom used for autoimmune diseases. Researchers only use it for the treatment of multiple sclerosis (MS, an autoimmune disease of the central nervous system). SLE is a kind of autoimmune diseases which involving multiple systems, organs and with the present of a variety of autoantibodies. In the conventional treatment options, SLE could be treated with chemotherapy drugs or hormone drugs. But chemotherapy and hormone drugs could barely cured SLE. And now, chimeric antigen receptor modified T cell infusion maybe an effective treatment to solve these problems. The investigators use a 2nd CAR- T with the optimized hinge and transmembrane domain to treat patients with SLE. The purpose of this study is to assess the safety and efficacy of this 2nd CAR-T cells in the treatment of SLE.
Detailed description
This study is being conducted to assess anti-CD19-CAR-T cells safety and efficacy in treating patients with systemic lupus erythematosus（SLE）.The investigators constructed a 2nd CAR, using CD19 as target, using 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge and transmembrane domain sequences. The infusion dose is (1-10)E6 CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Reduce B cells | Experimental | Drug: cyclophosphamidePatients receive cyclophosphamide to reduce B cells before CD19-CART infusion. It will also reduce the side effects of cell damage due to antitumor activity. |
| Treatment of SLE | Experimental | Drug: anti-CD19-CAR-T cellsPatients receive anti-CD19-CAR-T cells to treatment of SLE. The purpose of this study is to assess the safety and efficacy of CD19 CAR-T cells in the treatment of SLE. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Clinical diagnosis of systemic lupus erythematosus (SLE) patients
- Patients with CD19+ B-cell SLE as confirmed by Flow Cytometry
- Age: 18-69 years old
- Creatinine < 1.5 mg/dl
- cardiac ejection fraction>55%
Key exclusion criteria (6 listed)
- Pregnant or lactating women
- Uncontrolled active infection
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- Previously treatment with any gene therapy products
- Feasibility assessment during screening demonstrates<5% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation
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 |
|---|---|---|
| cyclophosphamideAlso: CyPatients receive cyclophosphamide (Cy) on day -2 and day -1 to reduce B cells. The dose is 0.5g/m2/d. | Drug | Reduce B cells |
| anti-CD19-CAR-T cellsAlso: 2nd CAR-TA 2nd CAR, CD19 as target protein, 4-1BB as co-stimulator, and optimized the spatial conformation by a suitable hinge \& transmembrane domain sequences. Patients infused with anti-CD19-CAR-T cells transduced with lentivirus on day 0 in the absence of disease progression or unacceptable toxicity to treatment of SLE. The dose is 1E6~1E7 CD19-CAR positive T cells. The cells infusion process may last for 30 min. | Drug | Treatment of SLE |
Primary outcome
Safety of CAR-T cell（i.v.）by number of patients with adverse event
Time frame: 6 weeks
adverse event is evaluated with CTCAE, version 4.0
2 secondary outcomes
Number of patients with tumor response
Time frame: 8 weeks
3. Detection of transferred T cells in the circulation using quantitative -PCR
Time frame: 6 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2017.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Qiang Guo, Doctor principal investigator
RenJi Hospital
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 cyclophosphamide and anti-CD19-CAR-T cells in people with Systemic Lupus Erythematosus (SLE), run by Shanghai GeneChem Co., Ltd. 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 10 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 7 Feb 2017. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qiang Guo, Doctor (86-21-63835620, bluedescent@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of CAR-T cell（i.v.）by number of patients with adverse event (time frame: 6 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 7 Feb 2017.