NeuroblastomaPhase 14SCAR-GD2NCT02765243
Anti-GD2 4th Generation CART Cells Targeting Refractory and/or Recurrent Neuroblastoma
A Phase 1 study testing Anti-GD2 CART in people with Neuroblastoma and Effects of Immunotherapy, run by Zhujiang Hospital at 1 site in China.
Trial summary
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. The investigators are attempt to treat this disease using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (CAR)… Read more about this study
- Who is it for?
- Ages 1 year to 14 years
- Conditions the study is for
- Neuroblastoma, Effects of Immunotherapy
- What is being tested?
- Anti-GD2 CART
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2016to 30 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients with neuroblastoma have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive/persistent or recurrent.
- The GD2 antigen status of the neuroblastoma will be determined for eligibility. Positive expression is defined by GD2 antibody staining results based on immunohistochemistry or flow cytometry analyses.
- Body weight greater than or equal to 10 kg.
- Age: ≥1 year and ≤ 14 years of age at the time of enrollment.
- Life expectancy: at least 8 weeks.
- Prior Therapy: 1) 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. 2) Must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection. 3) At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic nonmyelosuppressive regimen. 4) At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody. 5) At least 1 weeks since any radiation therapy at the time of study entry.
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- 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.
- Patients must have autologous transduced T cells at levels greater than or equal to 2x10e5 cells per kilogram body weight.
- For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.
Who cannot join
- 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-CAR T cells.
- Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
- Patients who require systemic corticosteroid or other immunosuppressive therapy.
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- Patients previously experienced severe toxicity from cyclophosphamide or fludarabine.
- Evidence of tumor potentially causing airway obstruction.
- Inability to comply with protocol requirements.
- Insufficient CAR T cells availability.
Trial locations and contacts
1 site in 1 country.
China1 site
Zhujiang Hospital of Southern Medical University
Guangzhou, Guangdong, 510282
About this study
Official title: Anti-GD2 4th Generation Chimeric Antigen Receptor-modified T Cells (4SCAR-GD2) Targeting Refractory and/or Recurrent Neuroblastoma
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. The investigators are attempt to treat this disease using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (CAR) targeting GD2 (4SCAR-GD2). The 4SCAR-GD2-modified T cells can recognize and kill neuroblastoma through the recognition of GD2, a surface protein expressed at high levels on neuroblastoma but not on normal tissues. This study will evaluate the side effects and effective doses of 4SCAR-GD2 T cells in treating refractory and/or recurrent neuroblastoma.
Read the detailed description
Background:
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a 4th generation GD2-specific chimeric antigen receptor (4SCAR-GD2). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill neuroblastoma through the recognition of a surface antigen, GD2, which is expressed at high levels in neuroblastoma but not at significant levels on normal tissues. This study will evaluate the side effects and the best dose of a novel 4th generation anti-GD2 CAR T cells to refractory and/or recurrent neuroblastoma.
Objectives:
- Primary: To determine the safety and feasibility of administration of 4SCAR-GD2 T cells to children with neuroblastoma following a cyclophosphamide/fludarabine preparative regimen.
- Secondary:
- To determine if the administration of 4SCAR-GD2 T cells can establish an antitumor effects in children with neuroblastoma who receive preparative regimen.
- To describe the toxicity of administration of anti-GD2 CAR T cells in children with or without high-burden disease.
- To evaluate the incidence and the treatment effect of cytokine release syndrome (CRS).
- To determine the expansion and functional persistence of 4SCAR-GD2 T cells in the peripheral blood of patients and the correlation with antitumor effects.
Eligibility:
Patients 1-14 years of age, at least 10 kg, with neuroblastoma that has recurred after or not responded to standard therapy and is deemed incurable by standard therapy.
Design:
- Participants will be screened through physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow aspirates may be performed.
- Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells will be activated and modified to express the 4SCAR-GD2 gene.
- On Day -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR-GD2 lentiviral transduction. The total culture time is approximately 5-10 days.
- Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accept the modified CAR T cells. The preparative regimen is consisted of fludarabine 25 mg/m(2) on days -4, -3 and -2 and cyclophosphamide 300 mg/m(2) on day-4, -3 and -2.
- Participants will receive an infusion of the modified 4SCAR-GD2 T cells and closely followed up for treatment related responses.
- Participants will have frequent follow-up visits to monitor the outcome of the treatment.
- Conditions
- Neuroblastoma, Effects of Immunotherapy
- Being tested
- Anti-GD2 CART
- Keywords
- neuroblastoma, GD2, Chimeric antigen receptor, Immunotherapy, Cyclophosphamide, Fludarabine
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-GD2 CARTBiological
Anti-GD2 4th Generation Chimeric Antigen Receptor-modified T Cells
| Study group | Role | What they receive |
|---|---|---|
| effectiveness of Anti-GD2 CART | Experimental | Anti-GD2 CART cells can recognize and kill neuroblastoma through the recognition of GD2. This study will evaluate the side effects and effective doses of Anti-GD2 CART cells in treating refractory and/or recurrent neuroblastoma Receives: Biological: Anti-GD2 CART |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events.
Determine the toxicity profile of the 4SCAR-GD2-modified T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
Measured: 1yr
Secondary outcomes (3)
Anti-tumor effects
Response will be determined by the evaluation of CT/MRI scans and bone marrow biopsy. Assessment of tumour response from baseline according to International Neuroblastoma Response Criteria (INRC).
Measured: 1yr
To evaluate the expansion and persistence of anti-GD2 CAR T cells
Investigators will monitor the expansion and functional persistence of 4SCAR-GD2 T cells in the peripheral blood of patients and the correlation with antitumor effects.
Measured: 1yr
Survival time of the patients
Evaluate the survival time of the patients treated with the 4SCAR-GD2 T cells, including progression free survival (PFS) and overall survival (OS)
Measured: 1yr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2016 (estimated)
- Study start1 Jan 2016
- Primary completion12 Jan 2019
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Zhujiang HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zhujiang Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yang Lihua, Zhujiang Hospital
- Investigators
- Lihua Yang, M.D., Ph.D., Principal investigator, Southern Medical University, ChinaLung-Ji Chang, Ph.D., Study director, Shenzhen Genoimmune Medical Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02765243
- Sponsor's protocol ID
- 2016-EKZX-001
- Acronym
- 4SCAR-GD2
- Status last verified
- Aug 2021
- First submitted
- 3 May 2016
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-GD2 4th Generation Chimeric Antigen Receptor-modified T Cells (4SCAR-GD2) Targeting Refractory and/or Recurrent Neuroblastoma
- ClinicalTrials.gov ID
- NCT02765243
- Acronym / sponsor ID
- 4SCAR-GD2 / 2016-EKZX-001
- Conditions
- Neuroblastoma, Effects of Immunotherapy
- Keywords
- neuroblastoma, GD2, Chimeric antigen receptor, Immunotherapy, Cyclophosphamide, Fludarabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Zhujiang HospitalUniversity, hospital or other
- Study start
- 1 Jan 2016 (actual)
- Primary completion
- 12 Jan 2019 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 6 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. The investigators are attempt to treat this disease using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (CAR) targeting GD2 (4SCAR-GD2). The 4SCAR-GD2-modified T cells can recognize and kill neuroblastoma through the recognition of GD2, a surface protein expressed at high levels on neuroblastoma but not on normal tissues. This study will evaluate the side effects and effective doses of 4SCAR-GD2 T cells in treating refractory and/or recurrent neuroblastoma.
Detailed description
Background:
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a 4th generation GD2-specific chimeric antigen receptor (4SCAR-GD2). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill neuroblastoma through the recognition of a surface antigen, GD2, which is expressed at high levels in neuroblastoma but not at significant levels on normal tissues. This study will evaluate the side effects and the best dose of a novel 4th generation anti-GD2 CAR T cells to refractory and/or recurrent neuroblastoma.
Objectives:
- Primary: To determine the safety and feasibility of administration of 4SCAR-GD2 T cells to children with neuroblastoma following a cyclophosphamide/fludarabine preparative regimen.
- Secondary:
- To determine if the administration of 4SCAR-GD2 T cells can establish an antitumor effects in children with neuroblastoma who receive preparative regimen.
- To describe the toxicity of administration of anti-GD2 CAR T cells in children with or without high-burden disease.
- To evaluate the incidence and the treatment effect of cytokine release syndrome (CRS).
- To determine the expansion and functional persistence of 4SCAR-GD2 T cells in the peripheral blood of patients and the correlation with antitumor effects.
Eligibility:
Patients 1-14 years of age, at least 10 kg, with neuroblastoma that has recurred after or not responded to standard therapy and is deemed incurable by standard therapy.
Design:
- Participants will be screened through physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow aspirates may be performed.
- Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells will be activated and modified to express the 4SCAR-GD2 gene.
- On Day -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR-GD2 lentiviral transduction. The total culture time is approximately 5-10 days.
- Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accept the modified CAR T cells. The preparative regimen is consisted of fludarabine 25 mg/m(2) on days -4, -3 and -2 and cyclophosphamide 300 mg/m(2) on day-4, -3 and -2.
- Participants will receive an infusion of the modified 4SCAR-GD2 T cells and closely followed up for treatment related responses.
- Participants will have frequent follow-up visits to monitor the outcome of the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| effectiveness of Anti-GD2 CART | Experimental | Biological: Anti-GD2 CARTAnti-GD2 CART cells can recognize and kill neuroblastoma through the recognition of GD2. This study will evaluate the side effects and effective doses of Anti-GD2 CART cells in treating refractory and/or recurrent neuroblastoma |
Who may qualify
- Ages
- 1 year to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (15 listed)
- Patients with neuroblastoma have received standard first-line therapy and been judged to be non-resectable, metastatic, progressive/persistent or recurrent.
- The GD2 antigen status of the neuroblastoma will be determined for eligibility. Positive expression is defined by GD2 antibody staining results based on immunohistochemistry or flow cytometry analyses.
- Body weight greater than or equal to 10 kg.
- Age: ≥1 year and ≤ 14 years of age at the time of enrollment.
- Life expectancy: at least 8 weeks.
Key exclusion criteria (10 listed)
- 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-CAR T cells.
- Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-GD2 CARTAnti-GD2 4th Generation Chimeric Antigen Receptor-modified T Cells | Biological | effectiveness of Anti-GD2 CART |
Primary outcome
Number of patients with adverse events.
Time frame: 1yr
Determine the toxicity profile of the 4SCAR-GD2-modified T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.
3 secondary outcomes
Anti-tumor effects
Time frame: 1yr
To evaluate the expansion and persistence of anti-GD2 CAR T cells
Time frame: 1yr
Survival time of the patients
Time frame: 1yr
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lihua Yang, M.D., Ph.D. principal investigator
Southern Medical University, China
Lung-Ji Chang, Ph.D. study director
Shenzhen Genoimmune Medical Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anti-GD2 CART in people with Neuroblastoma and Effects of Immunotherapy, run by Zhujiang Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with adverse events. (time frame: 1yr). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.