Combination CAR-T Cell Therapy Targeting Hematological Malignancies
NCT ID: NCT03125577
Last Updated: 2025-09-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
100 participants
INTERVENTIONAL
2025-08-01
2029-12-31
Brief Summary
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Detailed Description
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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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
4SCAR19 and 4SCAR22
4SCAR19 and 4SCAR22
4SCAR19 and 4SCAR38
4SCAR19 and 4SCAR38
4SCAR19 and 4SCAR20
4SCAR19 and 4SCAR20
4SCAR19 and 4SCAR123
4SCAR19 and 4SCAR123
4SCAR19 and 4SCAR70
4SCAR19 and 4SCAR70
4SCAR19 and 4SCAR30
4SCAR19 and 4SCAR30
Interventions
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4SCAR19 and 4SCAR22
4SCAR19 and 4SCAR22
4SCAR19 and 4SCAR38
4SCAR19 and 4SCAR38
4SCAR19 and 4SCAR20
4SCAR19 and 4SCAR20
4SCAR19 and 4SCAR123
4SCAR19 and 4SCAR123
4SCAR19 and 4SCAR70
4SCAR19 and 4SCAR70
4SCAR19 and 4SCAR30
4SCAR19 and 4SCAR30
Eligibility Criteria
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Inclusion Criteria
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
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.
6 Months
75 Years
ALL
No
Sponsors
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Shenzhen Geno-Immune Medical Institute
OTHER
Responsible Party
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Lung-Ji Chang
President
Principal Investigators
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Lung-Ji Chang, PhD
Role: PRINCIPAL_INVESTIGATOR
Shenzhen Geno-Immune Medical Institute
Locations
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Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Shenzhen Geno-immune Medical Institute
Shenzhen, Guangdong, China
Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
Kunming, Yunnan, China
Countries
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Central Contacts
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Facility Contacts
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References
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Nair S, Wang JB, Tsao ST, Liu Y, Zhu W, Slayton WB, Moreb JS, Dong L, Chang LJ. Functional Improvement of Chimeric Antigen Receptor Through Intrinsic Interleukin-15Ralpha Signaling. Curr Gene Ther. 2019;19(1):40-53. doi: 10.2174/1566523218666181116093857.
Other Identifiers
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GIMI-IRB-17005
Identifier Type: -
Identifier Source: org_study_id
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