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Combination CAR-T Cell Therapy Targeting Hematological Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03125577
Recruitment Status : Unknown
Verified September 2019 by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute.
Recruitment status was:  Recruiting
First Posted : April 24, 2017
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Study Description
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Brief Summary:
The study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells targeting CD19 (4SCAR19) and CD20 (4SCAR20), CD22 (4SCAR22), CD30 (4SCAR30), CD38 (4SCAR38), CD70 (4SCAR70) or CD123 (4SCAR123) for patients with B cell malignancies. 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 Malignancies Biological: 4SCAR19 and 4SCAR22 Biological: 4SCAR19 and 4SCAR38 Biological: 4SCAR19 and 4SCAR20 Biological: 4SCAR19 and 4SCAR123 Biological: 4SCAR19 and 4SCAR70 Biological: 4SCAR19 and 4SCAR30 Phase 1 Phase 2

Detailed Description:

Background:

T cells modified with lentiviral chimeric antigen receptor (CAR) gene have been studied in different clinical settings. Recent successes suggest that increased costimulatory signaling in the CAR design is critical for long term efficacy. Several clinical reports indicate that many patients still relapse and developed CD19-negative cancer cells after CD19 targeted therapy. Thus, to prevent the target escapes and improve the therapeutic effects, CAR gene-modified T cells targeting CD20, CD22, CD30, CD38, CD70 or CD123 are considered to apply together with CD19 CAR-T cells.

Activation of T cell response to high tumor burden may induce a severe response. To increase safety, a novel design using an inducible caspase 9 fusion gene has been incorporated in the CAR gene. A 4th generation CAR lentiviral vector (4SCAR) carrying multiple costimulatory signals for CD28/CD137/CD27 plus an inducible apoptotic caspase 9 gene has been established. This study aims to evaluate the activities of a combination of CAR gene-modified T cells to target cancer cells based on specific CD19/CD20/CD22/CD30/CD38/CD70/CD123 single chain antibody gene designs (4SCAR19/20/22/30/38/70/123).

Objective:

To evaluate safety and efficacy of administrating 4SCAR19, 4SCAR20, 4SCAR22, 4SCAR30, 4SCAR38, 4SCAR70 and 4SCAR123 T cells to patients with mixed CD19 positive and negative B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.

Eligibility:

Patients older than 6-month-old with CD19 positive or negative B cell malignancies that have recurred after or refractory to standard therapy and is deemed incurable using standard treatment.

Design:

Participants will be screened based on cancer cell phenotype analyzed using flow cytometry or immunohistochemical staining methods. Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis. On Day -5 to -7, T cells from PBMC will be activated and enriched, which will be followed by 4SCAR19, 4SCAR20, 4SCAR22, 4SCAR30, 4SCAR38, 4SCAR70 and 4SCAR123 lentiviral transduction. The total cell preparation time is approximately 5-7 days. Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accommodate the modified CAR T cells. The preparative regimen will depend on the immune condition of patients, which is consistent with standard chemotherapy conditioning regimen. Participants will receive an infusion of the modified 4SCAR19 and 4SCAR20/22/30/38/70/123 T cells and closely followed up for treatment-related responses. Participants will be continuously monitored for CAR T cells and clinical responses in a preset timeline.

Study Design
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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: Combination CAR-T Therapy of 4SCAR19 Plus 4SCAR20, 22, 38, 70 and 123 Targeting Hematological Malignancies
Actual Study Start Date : July 15, 2017
Actual Primary Completion Date : July 31, 2019
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Scars

Arms and Interventions
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Arm Intervention/treatment
Experimental: 4SCAR19 and 4SCAR20/CD22/CD30/CD38/CD70/CD123
Patients who have relapsed and refractory B cell malignancies after chemotherapy will be treated with CD19 and CD20/CD22/CD30/CD38/CD70/CD123-specific gene-engineered T cells.
 Biological: 4SCAR19 and 4SCAR22
4SCAR19 and 4SCAR22

Biological: 4SCAR19 and 4SCAR38
4SCAR19 and 4SCAR38

Biological: 4SCAR19 and 4SCAR20
4SCAR19 and 4SCAR20

Biological: 4SCAR19 and 4SCAR123
4SCAR19 and 4SCAR123

Biological: 4SCAR19 and 4SCAR70
4SCAR19 and 4SCAR70

Biological: 4SCAR19 and 4SCAR30
4SCAR19 and 4SCAR30


Outcome Measures
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Primary Outcome Measures :
  1. Safety of fourth generation anti CD19 and CD20/CD22/CD30/CD38/CD70/CD123 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events standard to evaluate the level of adverse events [ Time Frame: 24 weeks ]
    physiological parameter (for safety, measuring cytokine response, fever, symptoms)


Secondary Outcome Measures :
  1. Anti tumor activity of fourth generation anti CD19 and CD20/CD22/CD30/CD38/CD70/CD123 CAR-T cells in patients with relapsed or refractory B cell malignancies [ Time Frame: 1 year ]
    scale of CAR copies and leukemic cell burden (for efficacy)


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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. malignant B cell surface expression of CD19/CD20/CD22/CD30/CD38/CD70/CD123 molecules.
  3. the KPS score over 80 points, and survival time is more than 1 month.
  4. greater than Hgb 80 g/L.
  5. no contraindications to blood cell collection.

Exclusion Criteria:

  1. accompanied with other active diseases, the treatment is difficult to assess patient response.
  2. bacteria, fungus, or virus infection, unable to control.
  3. living with HIV.
  4. active HBV and HCV infection.
  5. pregnant and nursing mothers.
  6. under systemic steroid treatment within a week of the treatment.
  7. prior failed CAR-T treatment.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03125577


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   
Zhujiang Hospital of Southern Medical University Recruiting
Guangzhou, Guangdong, China, 510282
Contact: Lihua Yang, M.D., Ph.D.    +86-13580532469    dryanglihua@163.com   
Shenzhen Geno-immune Medical Institute Recruiting
Shenzhen, Guangdong, China, 518000
Contact: Lung-Ji Chang, PhD    86-13671121909    c@szgimi.org   
China, Yunnan
Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center Recruiting
Kunming, Yunnan, China, 650000
Contact: Xun Lai, MD    86-13577096609    1729112214@qq.com   
Sponsors and Collaborators
Shenzhen Geno-Immune Medical Institute
Investigators
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Principal Investigator: Lung-Ji Chang, PhD Shenzhen Geno-Immune Medical Institute
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute
ClinicalTrials.gov Identifier: NCT03125577    
Other Study ID Numbers: GIMI-IRB-17005
First Posted: April 24, 2017    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute:
4S CAR-T
CD19
CD20
CD22
CD38
 CD123
B cell leukemia
B-ALL
CD70
CD30
Additional relevant MeSH terms:
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Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases