4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma
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|ClinicalTrials.gov Identifier: NCT04637503|
Recruitment Status : Recruiting
First Posted : November 19, 2020
Last Update Posted : November 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Biological: GD2, PSMA and CD276 CAR-T cells||Phase 1 Phase 2|
Neuroblastoma is one of the most aggressive childhood tumors arising from neural crest cells. Nearly 50% of patients with high risk disease have poor long-term survival even after multimodal treatments. Novel immunotherapy targeting tumor-specific antigens has been developed to meet the desperate need.
Disialoganglioside (GD2) is a well-studied tumor associated antigen which is expressed uniformly in NB but restrictedly in normal tissue. Over the past few years, CAR-T therapy against GD2 in NB has achieved encouraging but modest outcomes. Only a fraction of patients achieved measurable responses. Like for many other solid tumors, CAR-T therapy for NB is not as effective as for hematologic malignancies.
In this study, the investigators use "multiple targeting" approach as the strategy to overcome the challenge in treating NB. Prostate-specific membrane antigen (PSMA) is expressed in normal prostate but is upregulated in prostate tumor. However, PSMA expression is not restricted to prostate cancer. By immunohistochemistry (IHC) staining, the investigators confirmed that PSMA is expressed in a variety of solid tumors, including brain tumor, neuroblastoma and some lymphoma tumor tissues. Therefore, PSMA could potentially serve as a promising target for antigen-specific immunotherapy in patients with NB. In addition, CD276 (B7-H3) is an immune checkpoint molecule highly expressed on many solid tumors including NB. CD276 has been characterized to be involved in tumor evasion and thus its expression is correlated with poor prognosis. These characteristics make CD276 an attractive candidate for immunotherapy. Given the significant variation of tumor antigen expression among patients, the investigators aim to examine GD2, PSMA and CD276 expression in each patient's tumor sections by IHC staining, and combine two or three highly-expressed targets for the 4SCAR-T therapy. This individualized and multi-antigen-targeted approach is a new strategy to overcome the limited clinical outcome in the 4SCAR-T therapy against NB.
The purpose of this clinical study is to assess the feasibility, safety and efficacy of the combinational GD2, PSMA and CD276 4SCAR-T cell therapy against NB. Another goal of the study is to learn more about the function of the multi-4SCAR-T cells and their persistency in the patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multi-center Phase I/II Clinical Trial of 4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma|
|Estimated Study Start Date :||November 18, 2020|
|Actual Primary Completion Date :||November 19, 2020|
|Estimated Study Completion Date :||December 31, 2023|
Experimental: effectiveness of CAR-T cells targeting GD2, PSMA and CD276
Gene-modified T cells are designed to kill tumor cells through specific recognition of GD2, PSMA and CD276. This study will evaluate the side effects and effective doses of GD2, PSMA and CD276 CAR-T cells in treating refractory and recurrent NB
Biological: GD2, PSMA and CD276 CAR-T cells
infusion, for 1x10^6~1x10^7 cells/kg via IV
- Number of patients with adverse events [ Time Frame: 3 year ]Determine the toxicity profile the GD2, PSMA and CD276 4SCAR-T cells with Common Toxicity Criteria for Adverse Effects version 4.0
- Anti-tumor effects [ Time Frame: 3 year ]Complete response/remission (CR), Very good partial response/remission (VGPR) will be assessed by the image scan
- The expansion of CAR-T cells [ Time Frame: 3 year ]The investigators will monitor the expansion of GD2, PSMA and CD276 CAR-T cells in the peripheral blood of patients and the correlation with antitumor effects.
- The anti-tumor activity after CAR-T infusions [ Time Frame: 1 year ]The anti-tumor activity of lymphocytes will be assessed
- The cytokine secretion profile after CAR-T infusions [ Time Frame: 1 year ]The cytokine secretion profile of lymphocytes will be assessed.
- Survival time of the patients [ Time Frame: 3 year ]The overall survival time of the patients treated with CAR-T cells
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): NCT04637503
|Contact: Lung-Ji Chang, PhDemail@example.com|
|Guangdong Zhujiang Hospital of Southern Medical University||Recruiting|
|Guangzhou, Guangdong, China, 510282|
|Contact: Lihua Yang, M.D, PhD 86-13580532469 firstname.lastname@example.org|
|Contact: Lihua Yu, M.D 86-13414125621 email@example.com|
|Shenzhen Children's Hospital||Recruiting|
|Shenzhen, Guangdong, China, 518000|
|Contact: Xiuli Yuan, M.D 86-18938690212 firstname.lastname@example.org|
|Shenzhen Geno-Immune Medical Institute||Recruiting|
|Shenzhen, Guangzhou, China, 518000|
|Contact: Lung-Ji Chang, PhD +86-13671121909 email@example.com|
|Shandong Cancer Hospital||Recruiting|
|Jinan, Shandong, China, 250022|
|Contact: Jingfu Wang, M.D, Ph.D 86-13821271562 firstname.lastname@example.org|