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Clinical Study of Targeting CD7 CAR-T Cells in the Treatment of Autoimmune Diseases

Primary Purpose

Crohn Disease, Ulcerative Colitis, Dermatomyositis

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
CD7 CAR T-cells
Sponsored by
Zhejiang University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn Disease focused on measuring CAR T-cell therapy, CD7, Crohn disease, Ulcerative colitis, Dermatomyositis, Still disease, Refractory autoimmune disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Diagnosed as refractory Crohn disease, ulcerative colitis (collectively called Crohn's disease), and the conventional hormone therapy is not effective and (or) there is no effective treatment:

    1. At least 6 months before screening, diagnosed as Crohn's disease based on typical radiological results and/or typical histology.
    2. In addition to corticosteroids, after the use of immunosuppressive agents (usually azathioprine, methotrexate, and two biological agents (usually infliximab, adalimumab and/or setolizumab), the course of the disease is still Unsatisfactory. Patients should still have relapsed and refractory diseases after glucocorticoid and/or immunosuppressive treatment, or clearly show intolerance/toxicity to these drugs
  2. Diagnosed as refractory dermatomyositis, and conventional hormone therapy is not effective and (or) ineffective treatment methods:

    1. At least 6 months before screening, confirmed or possible dermatomyositis according to Bohan and Peter criteria;
    2. At least it has no response to prednisone and other first-line immunosuppressants (such as methotrexate, mycophenolate mofetil, or azathioprine), or has obvious toxicity or intolerance to these therapies.
  3. Refractory adult STILL disease

    1. Conform the diagnostic criteria for adult STILL disease (according to Yamaguchi et al., J. Rheumatology, 1992);
    2. After receiving non-steroidal anti-inflammatory drugs, glucocorticoids, anti-rheumatic drugs (DMARDs) and other treatments, there are still relapsed and refractory diseases, or clearly show that these drugs are intolerant/toxic.
  4. Rheumatoid arthritis

    1. Conform the diagnostic criteria for rheumatoid arthritis in 2010 ACR classification criteria;
    2. Have received DMARDs or glucocorticoid therapy, but failed to achieve clinical remission, or clearly showed intolerance/toxicity to these drugs.

    The following screening can be performed by meeting any of the above 4 entry criteria

  5. Estimated survival time> 12 weeks;
  6. Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up;
  7. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

  • Subjects with any of the following exclusion criteria were not eligible for this trial:

    1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
    2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
    3. Pregnant (or lactating) women;
    4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
    5. Active infection of hepatitis B virus or hepatitis C virus;
    6. Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids);
    7. Those who have used any gene therapy products before.
    8. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
    9. Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl;
    10. Those who suffer from other uncontrolled diseases are not suitable to join the study;
    11. HIV infection;
    12. Any situation that the researchers believe may increase the risk of patients or interfere with the test results.

Sites / Locations

  • The first affiliated hospital of medical college of zhejiang universityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Crohn Disease

Ulcerative Colitis

Dermatomyositis

Still Disease

Autoimmune Diseases

Arm Description

Outcomes

Primary Outcome Measures

Dose-limiting toxicity (DLT)
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)
Incidence of treatment-emergent adverse events [Safety and Tolerability]

Secondary Outcome Measures

Overall response rate (ORR)
Proportion of subjects with complete or partial remission
Best overall response, BOR
Assessment of ORR at ≤3 month
Concentration of CAR-T cells
In peripheral blood and bone marrow
Duration of remission, DOR
The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause
Overall survival (OS)
The time from the cell reinfusion to death due to any cause

Full Information

First Posted
December 1, 2021
Last Updated
February 13, 2022
Sponsor
Zhejiang University
Collaborators
Yake Biotechnology Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05239702
Brief Title
Clinical Study of Targeting CD7 CAR-T Cells in the Treatment of Autoimmune Diseases
Official Title
A Clinical Study on the Safety and Effectiveness of Targeting CD7 Chimeric Antigen Receptor T Cells in the Treatment of Autoimmune Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 28, 2022 (Anticipated)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University
Collaborators
Yake Biotechnology Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A Clinical Study on the Safety and Effectiveness of Targeting CD7 Chimeric Antigen Receptor T Cells in the Treatment of Autoimmune Diseases
Detailed Description
Most patients with autoimmune diseases depend on hormones for life, and when poorly controlled, they are at risk of disability or even death. Studies have found that the abnormal T cell function of patients is closely related to the occurrence and development of the disease. Therefore, reducing the T cells in the patient's body or blocking the function has become the latest breakthrough in treatment. CD7 is a specific antigen on the surface of T cells. CD7 CAR-T can specifically attack T cells and has the potential to cure. In 2019, "Science Translational Medicine" magazine reported that the Marko Radic team demonstrated that CAR-T cells can achieve significant and long-lasting effects in the treatment of systemic lupus erythematosus (SLE) through animal experiments. In 2021, "NEJM" magazine reported the clinical efficacy of CAR-T cells in the treatment of SLE. In the same year, "Journal of Clinical Oncology" reported the clinical efficacy and safety of CD7 CAR-T cells in the treatment of T cell ALL. Based on the current research status, we applied to clinical research on the treatment of refractory autoimmune diseases by targeting CD7 CAR-T cells. The selection criteria is patients with refractory autoimmune diseases. The purpose is to evaluate the safety and effectiveness of targeted CD7 CAR-T cell therapy through this clinical trial study, and to provide clinical evidence and experience reference for the application of CAR-T cell technology in the treatment of refractory autoimmune diseases.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease, Ulcerative Colitis, Dermatomyositis, Still Disease, Autoimmune Diseases
Keywords
CAR T-cell therapy, CD7, Crohn disease, Ulcerative colitis, Dermatomyositis, Still disease, Refractory autoimmune disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Crohn Disease
Arm Type
Experimental
Arm Title
Ulcerative Colitis
Arm Type
Experimental
Arm Title
Dermatomyositis
Arm Type
Experimental
Arm Title
Still Disease
Arm Type
Experimental
Arm Title
Autoimmune Diseases
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
CD7 CAR T-cells
Other Intervention Name(s)
CD7 CAR-T cells injection
Intervention Description
Each subject receive CD7 CAR T-cells by intravenous infusion
Primary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT)
Description
Adverse events assessed according to NCI-CTCAE v5.0 criteria
Time Frame
Baseline up to 28 days after CD7 targeted CAR T-cells infusion
Title
Incidence of treatment-emergent adverse events (TEAEs)
Description
Incidence of treatment-emergent adverse events [Safety and Tolerability]
Time Frame
Up to 2 years after CD7 targeted CAR T-cells infusion
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Proportion of subjects with complete or partial remission
Time Frame
At Month 1, 3, 6, 12, 18, 24
Title
Best overall response, BOR
Description
Assessment of ORR at ≤3 month
Time Frame
At ≤3 month
Title
Concentration of CAR-T cells
Description
In peripheral blood and bone marrow
Time Frame
From admission to the end of the follow-up, up to 2 years
Title
Duration of remission, DOR
Description
The time from the first assessment of remission or partial remission of the disease to the first assessment of disease progression or death from any cause
Time Frame
2 years post CD7 CAR-T cells infusion
Title
Overall survival (OS)
Description
The time from the cell reinfusion to death due to any cause
Time Frame
From CD7 CAR-T infusion to death,up to 2 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosed as refractory Crohn disease, ulcerative colitis (collectively called Crohn's disease), and the conventional hormone therapy is not effective and (or) there is no effective treatment: At least 6 months before screening, diagnosed as Crohn's disease based on typical radiological results and/or typical histology. In addition to corticosteroids, after the use of immunosuppressive agents (usually azathioprine, methotrexate, and two biological agents (usually infliximab, adalimumab and/or setolizumab), the course of the disease is still Unsatisfactory. Patients should still have relapsed and refractory diseases after glucocorticoid and/or immunosuppressive treatment, or clearly show intolerance/toxicity to these drugs Diagnosed as refractory dermatomyositis, and conventional hormone therapy is not effective and (or) ineffective treatment methods: At least 6 months before screening, confirmed or possible dermatomyositis according to Bohan and Peter criteria; At least it has no response to prednisone and other first-line immunosuppressants (such as methotrexate, mycophenolate mofetil, or azathioprine), or has obvious toxicity or intolerance to these therapies. Refractory adult STILL disease Conform the diagnostic criteria for adult STILL disease (according to Yamaguchi et al., J. Rheumatology, 1992); After receiving non-steroidal anti-inflammatory drugs, glucocorticoids, anti-rheumatic drugs (DMARDs) and other treatments, there are still relapsed and refractory diseases, or clearly show that these drugs are intolerant/toxic. Rheumatoid arthritis Conform the diagnostic criteria for rheumatoid arthritis in 2010 ACR classification criteria; Have received DMARDs or glucocorticoid therapy, but failed to achieve clinical remission, or clearly showed intolerance/toxicity to these drugs. The following screening can be performed by meeting any of the above 4 entry criteria Estimated survival time> 12 weeks; Patients had a negative urine pregnancy test before the start of administration and agreed to take effective contraceptive measures during the test period until the last follow-up; Patients or their legal guardians volunteer to participate in the study and sign the informed consent. Exclusion Criteria: Subjects with any of the following exclusion criteria were not eligible for this trial: History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Active infection of hepatitis B virus or hepatitis C virus; Systemic steroids have used in the 4 weeks before participating in the treatment (except recently or currently using inhaled steroids); Those who have used any gene therapy products before. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; Serum creatinine > 2.5mg/dl or ALT / AST > 3 times ULN or bilirubin > 2.0mg/dl; Those who suffer from other uncontrolled diseases are not suitable to join the study; HIV infection; Any situation that the researchers believe may increase the risk of patients or interfere with the test results.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
He Huang, PhD
Phone
+8613605714822
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yongxian Hu, PhD
Phone
+8615957162012
Email
huyongxian2000@aliyun.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
He Huang, PhD
Organizational Affiliation
First Affiliated Hospital of Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The first affiliated hospital of medical college of zhejiang university
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
He Huang, PhD
Phone
86-13605714822
Email
hehuangyu@126.com
First Name & Middle Initial & Last Name & Degree
Yongxian Hu, PhD
Phone
+8615957162012
Email
huyongxian2000@aliyun.com

12. IPD Sharing Statement

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Clinical Study of Targeting CD7 CAR-T Cells in the Treatment of Autoimmune Diseases

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