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出境医 / 临床实验 / CAR-T Immunotherapy Targeting CD19- ALL

CAR-T Immunotherapy Targeting CD19- ALL

Study Description
Brief Summary:
This study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 negative ALL that express CD22, CD123, CD38, CD10, CD20 and TSLPR, as many patients developed CD19-negative disease after CD19 CART immunotherapy. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.

Condition or disease Intervention/treatment Phase
B-cell Leukemia Biological: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR Phase 1 Phase 2

Detailed Description:

Anti-CD19 chimeric antigen receptor T cell therapy has demonstrated unprecedented treatment responses in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, many studies have reported that a subset of patients still relapse and about 30-50% of those relapses are characterized by the loss of CD19 surface antigen. Patients with CD19-negative relapse after CD19 CAR-T-cell therapy usually have a poor prognosis. The mechanisms underlying CD19-negative relapses are not fully understood and it is important to develop solutions to supplement post-CD19 immunotherapies.

Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population include many known B-cell lineage antigens. To prevent further target escape and improve the therapeutic effects, CAR gene-modified T cells targeting CD22, CD123, CD38, CD10, CD20 or TSLPR have been considered in post CD19 CAR-T immunotherapy. This study aims to evaluate safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to patients with CD19-negative B cell malignancies.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CART Immunotherapy Targeting CD19 Negative Acute Lymphoblastic Leukemia
Actual Study Start Date : July 15, 2019
Estimated Primary Completion Date : July 15, 2021
Estimated Study Completion Date : December 15, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR
Patients who have relapsed after CD19 CART immunotherapy or have CD19 negative B cell malignancies
 Biological: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR
4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR Patients who have relapsed after CD19 CART immunotherapy or have CD19 negative B cell malignancies
Outcome Measures
Primary Outcome Measures :
  1. Safety of infusion [ Time Frame: 24 weeks ]
    Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.


Secondary Outcome Measures :
  1. Anti-tumor activity of CART [ Time Frame: 1 year ]
    Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry


Eligibility Criteria
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Ages Eligible for Study:   6 Months to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age older than 6 months.
  2. Native CD19 negative B cell malignancies or relapse after CD19-CAR-T immunotherapy.
  3. Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20/TSLPR.
  4. The KPS score over 80 points, and survival time is more than 1 month.
  5. Greater than Hgb 80 g/L.
  6. No contraindications to blood cell collection.

Exclusion Criteria:

  1. Complications with other active diseases, and difficult to assess patient response.
  2. Bacteria, fungus, or virus infection, and unable to control.
  3. Living with HIV.
  4. Active HBV and HCV infection.
  5. Pregnant and nursing mothers.
  6. Under systemic steroid use within a week of the treatment.
Contacts and Locations

Contacts
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Contact: Lung-Ji Chang, PhD +86-0755 8672-5195 c@szgimi.org

Locations
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China, Guangdong
Zhujiang Hospital of Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510282
Contact: Yuhua Li, M.D, Ph.D    86-13533706656    liyuhua2011gz@163.com   
Shenzhen Geno-immune Medical Institute Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, PhD    +86-0755 8672-5195    c@szgimi.org   
China, Hebei
Zhongxi Children Hospital Recruiting
Shijiazhuang, Hebei, China, 050006
Contact: Yaochen Zhang, M.D         
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
Investigators
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Principal Investigator: Lung-Ji Chang, PhD Shenzhen Geno-Immune Medical Institute
Tracking Information
First Submitted Date  ICMJE July 4, 2019
First Posted Date  ICMJE July 11, 2019
Last Update Posted Date September 19, 2019
Actual Study Start Date  ICMJE July 15, 2019
Estimated Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2019) 		Safety of infusion [ Time Frame: 24 weeks ]
Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2019) 		Anti-tumor activity of CART [ Time Frame: 1 year ]
Scale of CAR copies are detected by qPCR and leukemic cell burden are assessed by flow cytometry
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CAR-T Immunotherapy Targeting CD19- ALL
Official Title  ICMJE CART Immunotherapy Targeting CD19 Negative Acute Lymphoblastic Leukemia
Brief Summary This study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 negative ALL that express CD22, CD123, CD38, CD10, CD20 and TSLPR, as many patients developed CD19-negative disease after CD19 CART immunotherapy. Clinical response and development of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.
Detailed Description

Anti-CD19 chimeric antigen receptor T cell therapy has demonstrated unprecedented treatment responses in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, many studies have reported that a subset of patients still relapse and about 30-50% of those relapses are characterized by the loss of CD19 surface antigen. Patients with CD19-negative relapse after CD19 CAR-T-cell therapy usually have a poor prognosis. The mechanisms underlying CD19-negative relapses are not fully understood and it is important to develop solutions to supplement post-CD19 immunotherapies.

Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population include many known B-cell lineage antigens. To prevent further target escape and improve the therapeutic effects, CAR gene-modified T cells targeting CD22, CD123, CD38, CD10, CD20 or TSLPR have been considered in post CD19 CAR-T immunotherapy. This study aims to evaluate safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to patients with CD19-negative B cell malignancies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-cell Leukemia
Intervention  ICMJE Biological: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR
4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR Patients who have relapsed after CD19 CART immunotherapy or have CD19 negative B cell malignancies
Study Arms  ICMJE Experimental: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR
Patients who have relapsed after CD19 CART immunotherapy or have CD19 negative B cell malignancies
Intervention: Biological: 4SCAR-CD22/CD123/CD38/CD10/CD20/TSLPR
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 9, 2019) 		100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2023
Estimated Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age older than 6 months.
  2. Native CD19 negative B cell malignancies or relapse after CD19-CAR-T immunotherapy.
  3. Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20/TSLPR.
  4. The KPS score over 80 points, and survival time is more than 1 month.
  5. Greater than Hgb 80 g/L.
  6. No contraindications to blood cell collection.

Exclusion Criteria:

  1. Complications with other active diseases, and difficult to assess patient response.
  2. Bacteria, fungus, or virus infection, and unable to control.
  3. Living with HIV.
  4. Active HBV and HCV infection.
  5. Pregnant and nursing mothers.
  6. Under systemic steroid use within a week of the treatment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lung-Ji Chang, PhD +86-0755 8672-5195 c@szgimi.org
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04016129
Other Study ID Numbers  ICMJE GIMI-IRB-19003
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shenzhen Geno-Immune Medical Institute
Study Sponsor  ICMJE Shenzhen Geno-Immune Medical Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lung-Ji Chang, PhD Shenzhen Geno-Immune Medical Institute
PRS Account Shenzhen Geno-Immune Medical Institute
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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