A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03050190|
Recruitment Status : Recruiting
First Posted : February 10, 2017
Last Update Posted : September 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|B-cell Malignancies||Genetic: Therapeutic 4SCAR19 cells||Phase 1 Phase 2|
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. Activation of T cell response from large 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 T cell costimulatory signals for CD28/CD27 plus an inducible apoptotic caspase 9 gene has been established. The study aims to evaluate the activities of a new CAR gene-modified T cells targeting CD19-positive tumors based on a CD19-specific single chain gene constructed 4SCAR (4SCAR19).
To evaluate safety and efficacy of administrating 4SCAR19 T cells to patients with CD19 positive B cell malignancies following a cyclophosphamide/fludarabine based conditioning regimen.
Patients older than 6-month-old with CD19 positive B cells malignancies that have recurred after or refractory to standard therapy and is deemed incurable using standard treatment.
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, and T cells will be activated and modified to express the 4SCAR19 gene.
On Day -5 to -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR19 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 be based on patient immune condition and consistent with standard chemotherapy conditioning regimen.
Participants will receive an infusion of the modified 4SCAR19 T cells and closely followed up for treatment-related responses.
Participants will be continuously monitored for CAR T cells and clinical responses at present timeline.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Multiple Center Trial of 4SCAR19 Cells in the Treatment of Relapsed and Refractory B Cell Malignancies|
|Study Start Date :||July 2013|
|Actual Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||December 2020|
Experimental: Therapeutic 4SCAR19 cells
Patients who have relapsed and refractory B cell leukemia after chemotherapy will be treated prophylactically with CD19-specific gene-engineered T cells.
Genetic: Therapeutic 4SCAR19 cells
Autologous 4th generation withdrawal lentiviral-transduced 4S CAR-T19
- Safety of fourth generation anti CD19 CAR-T cells in patients with relapsed B cell malignancies using CTCAE 4 standard to evaluate the level of adverse events [ Time Frame: 24 weeks ]physiological parameter (for safety, measuring cytokine response, fever, symptoms)
- Anti tumor activity of fourth generation anti CD19 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)
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): NCT03050190
|Contact: Lung-Ji Chang, PhD||+86-0755 email@example.com|
|Shenzhen Geno-immune Medical Institute||Recruiting|
|Shenzhen, Guangdong, China, 518000|
|Contact: Lung-Ji Chang, PhD +86-13671121909 firstname.lastname@example.org|
|The First People's Hospital of Yunnan||Recruiting|
|Kunming, Yunnan, China, 650000|
|Contact: Xun Lai, MD 13577096609 email@example.com|
|Principal Investigator:||Lung-Ji Chang||Shenzhen Geno-Immune Medical Institute|