Ignite Creation Date:
2024-05-06 @ 9:57 AM
Last Modification Date:
2024-10-26 @ 12:22 PM
Study NCT ID:
NCT03125577
Status:
UNKNOWN
Last Update Posted:
2019-09-19
First Post:
2017-04-19
Brief Title:
Combination CAR-T Cell Therapy Targeting Hematological Malignancies
Sponsor:
Shenzhen Geno-Immune Medical Institute
Organization:
Shenzhen Geno-Immune Medical Institute
Study Overview
Official Title:
Combination CAR-T Therapy of 4SCAR19 Plus 4SCAR20 22 38 70 and 123 Targeting Hematological Malignancies
Status:
UNKNOWN
Status Verified Date:
2019-09
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 III trial enrolling patients from multiple clinical centers
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 CD28CD137CD27 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 CD19CD20CD22CD30CD38CD70CD123 single chain antibody gene designs 4SCAR192022303870123
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 cyclophosphamidefludarabine 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 cyclophosphamidefludarabine 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 4SCAR2022303870123 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
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 CD28CD137CD27 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 CD19CD20CD22CD30CD38CD70CD123 single chain antibody gene designs 4SCAR192022303870123
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 cyclophosphamidefludarabine 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 cyclophosphamidefludarabine 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 4SCAR2022303870123 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None