- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04637503
4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma
Multi-center Phase I/II Clinical Trial of 4SCAR-T Therapy Targeting GD2, PSMA and CD276 for Treating Neuroblastoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Lung-Ji Chang, PhD
- Phone Number: +86-8672-5195
- Email: c@szgimi.org
Study Locations
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Guangdong
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Guangzhou, Guangdong, China, 510282
- Recruiting
- Guangdong Zhujiang Hospital of Southern Medical University
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Contact:
- Lihua Yang, M.D, PhD
- Phone Number: 86-13580532469
- Email: dryanglihua@163.com
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Contact:
- Lihua Yu, M.D
- Phone Number: 86-13414125621
- Email: eveylhyu@gmail.com
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Shenzhen, Guangdong, China, 518000
- Recruiting
- Shenzhen Children's Hospital
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Contact:
- Xiuli Yuan, M.D
- Phone Number: 86-18938690212
- Email: 18938690212@163.com
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Guangzhou
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Shenzhen, Guangzhou, China, 518000
- Recruiting
- Shenzhen Geno-Immune Medical Institute
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Contact:
- Lung-Ji Chang, PhD
- Phone Number: +86-13671121909
- Email: c@szgimi.org
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Shandong
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Jinan, Shandong, China, 250022
- Recruiting
- Shandong Cancer Hospital
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Contact:
- Jingfu Wang, M.D, Ph.D
- Phone Number: 86-13821271562
- Email: wangjingfu666@163.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with tumors have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive or recurrent.
- The expression status of GD2, PSMA and CD276 antigens of the tumor will be determined for eligibility. Positive expression is defined by GD2, PMSA and CD276 antibody staining results based on immunohistochemistry or flow cytometry analyses.
- Body weight greater than or equal to 10 kg.
- Age: ≥1 year and ≤ 65 years of age at the time of enrollment.
- Life expectancy: at least 8 weeks.
Prior Therapy:
- There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must have resolved to grade 2 or less.
- Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
- At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressive regimen.
- At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody.
- At least 1 week since any radiation therapy at the time of study entry.
- Karnofsky/jansky score of 60% or greater.
- Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent.
- Pulse Ox greater than or equal to 90% on room air.
- Liver function: defined as alanine transaminase (ALT) <3x upper limit of normal (ULN), aspartate aminotransferase (AST) <3x ULN; serum bilirubin and alkaline phosphatase <2x ULN.
- Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
- Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
- Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease not evaluable for hematologic toxicity.
- For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.
Exclusion Criteria:
- Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, with the exception of grade 3 hematologic toxicity.
- Untreated central nervous system (CNS) metastasis: Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
- Previous treatment with other genetically engineered GD2, PSMA and CD276 CART cells.
- Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
- Patients who require systemic corticosteroid or other immunosuppressive therapy.
- Evidence of tumor potentially causing airway obstruction.
- Inability to comply with protocol requirements.
- Insufficient CART cells availability.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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
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infusion, for 1x10^6~1x10^7 cells/kg via IV
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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3 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anti-tumor effects
Time Frame: 3 year
|
Complete response/remission (CR), Very good partial response/remission (VGPR) will be assessed by the image scan
|
3 year
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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.
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3 year
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The anti-tumor activity after CAR-T infusions
Time Frame: 1 year
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The anti-tumor activity of lymphocytes will be assessed
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1 year
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The cytokine secretion profile after CAR-T infusions
Time Frame: 1 year
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The cytokine secretion profile of lymphocytes will be assessed.
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1 year
|
Survival time of the patients
Time Frame: 3 year
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The overall survival time of the patients treated with CAR-T cells
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3 year
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Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GIMI-IRB-20010
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neuroblastoma
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingStage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 Neuroblastoma | Stage 1 Neuroblastoma | Stage 2 NeuroblastomaUnited States, Canada, Australia, New Zealand
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Stage 4S Neuroblastoma | Stage 2A Neuroblastoma | Stage 2B Neuroblastoma | Stage 3 Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand
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National Cancer Institute (NCI)Active, not recruitingRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Stage 4 NeuroblastomaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)RecruitingLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S Neuroblastoma | Ganglioneuroblastoma | Stage 4 NeuroblastomaUnited States, Puerto Rico, Canada, Australia, New Zealand, Netherlands, Saudi Arabia, Switzerland
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4 NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedLocalized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Regional Neuroblastoma | Stage 4S NeuroblastomaUnited States
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Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Neuroblastoma | Disseminated Neuroblastoma | Localized Resectable Neuroblastoma | Localized Unresectable Neuroblastoma | Stage 4S NeuroblastomaUnited States
Clinical Trials on GD2, PSMA and CD276 CAR-T cells
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PersonGen BioTherapeutics (Suzhou) Co., Ltd.The First Affiliated Hospital of Zhengzhou UniversityNot yet recruitingGastric Cancer | Lung Cancer | Osteosarcoma | Neuroblastoma
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Shenzhen University General HospitalRecruitingAdvanced Pancreatic CarcinomaChina
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University College, LondonNot yet recruiting
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University College, LondonRecruiting
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Sinobioway Cell Therapy Co., Ltd.Children's Hospital of Fudan University; Nanjing Children's HospitalUnknownRelapsed or Refractory NeuroblastomaChina
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Shenzhen Geno-Immune Medical InstituteRecruiting
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Bambino Gesù Hospital and Research InstituteRecruitingHigh Grade Glioma | Medulloblastoma, Childhood | Diffuse Intrinsic Pontine Glioma | Diffuse Midline Glioma | Embryonal Tumor | Brain Tumor Adult | Brain Tumor, PediatricItaly
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Children's Mercy Hospital Kansas CityCenter for Cell and Gene Therapy, Baylor College of MedicineCompleted
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Poseida Therapeutics, Inc.Active, not recruitingNeoplasms | Neoplasms by Histologic Type | Urogenital Neoplasms | Neoplasms by Site | Genital Neoplasms, Male | Prostatic Neoplasms | Adenoid Cystic Carcinoma | Mucoepidermoid Carcinoma | Prostate Cancer | Prostatic Neoplasms, Castration-Resistant | Metastatic Castration-resistant Prostate Cancer | Neoplasms... and other conditionsUnited States
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Fuda Cancer Hospital, GuangzhouWithdrawnCAR-T Cell Immunotherapy | Glioma of Brain