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Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Immunomodulating Agents

Name:The Chimeric Antigen Receptor T Cell Immunotherapy (CAR-T) Dosage form：injection Dosage:100ml/time Frequency:0 days,the first day,the second day,29 days,30 days Duration:Total five times

This study have only one arm that is CAR-T experimental arm. Firstly all participators will be attended the screening, who passed the screening for the treatment of CAR-T cells, the CAR-GD2-modified T cells can recognize and kill tumor cells in the body，follow-up 35 months.

GD2-targeted CAR-T cells

Yongjun Fang, Ph.D

Kuiran Dong, Ph.D

This single-arm, multicenter clinical study will treat the patient who have relapsed or refractory neuroblastoma with an infusion of the patient's own T cells that have been genetically modified to express a chimeric antigen receptor(CAR)that will bind to tumour cells modified to express the GD2 protein on the cell surface. The study will determine if these modified T cells help the body's immune system eliminate tumour cells .The trial will also study the safety of treatment for CAR-T, how long CAR-T cells stay in the patient's body and the impact on this treatment for survival.

This is a single-arm, multicenter clinical study to evaluate efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) in the treatment of relapsed or refractory neuroblastoma in children. The study will be conducted using a phaseⅠ/Ⅱdesign the study will have the following sequential phases: part A (screening, leukapheresis,cell product preparation and cytoreductive chemotherapy) and part B (treatment and follow-up). the follow-up period for each participant is approximately 35 months after the final CAR-T infusion. The total duration of the study are expected to be approximately 3 years. A total of 22 patients may be enrolled over a period of 3 years.

Study Evaluating the Efficacy and Safety With CAR-T for Relapsed or Refractory Neuroblastoma in Children

Single Arm and Multicenter Clinical Trial to Evaluating the Efficacy and Safety of the Chimeric Antigen Receptor T Cell Immunotherapy (CAR-T) for Relapsed or Refractory Neuroblastoma in Children

The overall efficiency will be determined by the evaluation of CT/MRI scans and bone marrow biopsy. Assessment of tumor remission rate according to International Neuroblastoma Response Criteria. The overall efficiency = (complete remission (CR) number + the number of very good partial remission (VGPR) number + partial response (PR) number + mixed reaction (MR) number + no response (NR) number) / total number of cases receiving treatment.

From the test of the progression of disease progression or the interval between disease and death.

For all patients, overall survival refers to the period from being included in the test group to death caused by any reason

According to EORTC quality of life measurement scale PedsQL4.0_ children's quality of life of the core scale of the evaluation and comparison of physical condition before and after treatment.

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Nanjing Children's Hospital

Children's Hospital of Fudan University

Sinobioway Cell Therapy Co., Ltd.

Symptoms and General Pathology

Syndrome

Cytokine Release Syndrome

Gaucher Disease Type 2

Antineoplastic Agents

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients in Dose Level 1 will receive 1x10\^7 1RG-CART/m\^2 intravenously (IV) on Day 0.

Patients in Dose Level 2 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -4 to -1) followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Patients in Dose Level 3 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Patients in Dose Level 4 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^8 1RG-CART/m\^2 IV on Day 0.

If the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).

Patients who were enrolled and underwent leukapheresis but who did not receive any IMP.

Leukapheresis

1RG-CART

John Anderson, Prof

The purpose of this first in human study is to determine the safety and feasibility of 1RG-CART therapy in patients with relapsed or refractory neuroblastoma. 1RG-CART therapy is a novel immunotherapy under investigation in which patients have their T-cells (a type of white blood cell) collected and modified in the laboratory, before they are given back to the patient. The T-cells are modified to express a chimeric antigen receptor (CAR) which targets disialoganglioside (GD2), a marker expressed on the surface of neuroblastoma cells.

The purpose of this trial is to explore the safety and feasibility of deploying autologous anti-GD2 CAR T-cells for the immunotherapy of neuroblastoma. The CAR T-cell trials employing second generation receptors and lymphodepleting conditioning regimes have produced objective clinical responses in patients with relapsed leukaemias. The trial aims to evaluate similar CAR T-cells but directed against the antigen GD2. Neuroblastoma is well suited to this form of targeted therapy because of the homogeneous and almost universal expression of GD2 on the surface of neuroblastoma cells, and because of the poor prognosis of eligible patients.

1RG-CART will be administered intravenously. As the CAR T-cells are designed to survive and proliferate on encountering antigen, no direct relationship is anticipated between cell dose and either efficacy or toxicity. Rather, clinical benefit is more likely to be observed in those patients in whom in vivo expansion successfully occurs. A possible key determinant of expansion will be prior lymphodepletion of the patients. For this reason this trial is designed to evaluate a phased introduction of lymphodepletion in successive patient cohorts, rather than T-cell dose escalation. Only if there is insufficient expansion of T-cells following full lymphodepletion will the T-cell dose be escalated. Rituximab (MabThera®) will be used as a rescue medication only when necessary, and will be considered a non-investigational medicinal product (NIMP) in this trial.

A Phase I Trial of Anti-GD2 T-cells (1RG-CART)

A Cancer Research UK Phase I Trial of Anti-GD2 Chimeric Antigen Receptor (CAR) Transduced T-cells (1RG-CART) in Patients With Relapsed or Refractory Neuroblastoma

Feasibility of 1RG-CART therapy assessed as the number of patients who commence T-cell processing and are subsequently evaluable for 1RG-CART engraftment at Day 14.

Number of serious adverse events, non-serious adverse events and adverse events that are related to fludarabine, cyclophosphamide or 1RG-CART.

Number of dose limiting toxicities (DLTs) at each dose level.

Number of patients with 1RG-CART levels in peripheral blood above the limit of quantification for the assay (10 cells/µL) by flow cytometry.

Assessment of best tumour response from baseline according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.

Assessment of best tumour response from baseline according to Immune Related Response Criteria (irRC).

Assessment of best tumour response from baseline according to International Neuroblastoma Response Criteria (INRC).

Progression free survival (progression by RECIST criteria).

Cancer Research UK

Adverse events are reported for those patients who received IMP (fludarabine, cyclophosphamide or 1RG-CART) on the trial. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.02 or trial-specific (protocol defined) grading scheme for cytokine release syndrome (CRS) was used to grade AE severity.

Patients in Dose Level 1 will receive 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis

1RG-CART

Dose Level 1

Patients in Dose Level 2 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -4 to -1) followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis

Cyclophosphamide

1RG-CART

Dose Level 2

Patients in Dose Level 3 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis

Cyclophosphamide

Fludarabine

1RG-CART

Dose Level 3

Patients in Dose Level 4 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^8 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis

Cyclophosphamide

Fludarabine

1RG-CART

Dose Level 4

If the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).

Assigned Interventions:

Leukapheresis

Cyclophosphamide

Fludarabine

1RG-CART

Dose Level 5

Patients in Dose Level 3 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Cyclophosphamide

Fludarabine

Leukapheresis

1RG-CART

Patients in Dose Level 4 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^8 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Cyclophosphamide

Fludarabine

Leukapheresis

1RG-CART

If the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).

Assigned Interventions:

Cyclophosphamide

Fludarabine

Leukapheresis

1RG-CART

Patients who were enrolled and underwent leukapheresis but who did not receive any IMP.

Assigned Interventions:

Leukapheresis

Patients Who Underwent Leukapheresis But Did Not Proceed to Receive Any IMP

Total

Age, Categorical

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United Kingdom

Region of Enrollment

For the secondary outcome measure of Overall Survival, one patient from Dose Level 1 withdrew consent to continue with the trial, therefore the time to death (if applicable) for this patient was not collected.

Regulatory Affairs Manager

Patients in Dose Level 2 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -4 to -1) followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis Cyclophosphamide

1RG-CART/m\^2

Patients in Dose Level 3 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis Cyclophosphamide Fludarabine

1RG-CART/m\^2

Patients in Dose Level 4 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^8 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis Cyclophosphamide Fludarabine

1RG-CART/m\^2

If the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).

Assigned Interventions:

Leukapheresis Cyclophosphamide Fludarabine

1RG-CART/m\^2

All eligible patients enrolled for leukapheresis/venepuncture. Patients who were enrolled for leukapheresis/venepuncture in error (due to ineligibility or administrative error) were excluded.

To Evaluate the Feasibility of 1RG-CART Therapy in Patients With Relapsed or Refractory Neuroblastoma

SAEs

NSAEs

Fludarabine Related AEs

Cyclophosphamide Related AEs

1RG-CART Related AEs

Patients in Dose Level 3 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis

Cyclophosphamide

Fludarabine

1RG-CART/m\^2

Patients in Dose Level 4 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 1x10\^8 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis

Cyclophosphamide

Fludarabine

1RG-CART/m\^2

If the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).

Assigned Interventions:

Leukapheresis

Cyclophosphamide

Fludarabine

1RG-CART/m\^2

All eligible patients who received at least one dose of 1RG-CART, cyclophosphamide or fludarabine.

Safety and Tolerability of 1RG-CART Therapy

Patients in Dose Level 2 will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -4 to -1) followed by 1x10\^7 1RG-CART/m\^2 IV on Day 0.

Assigned Interventions:

Leukapheresis

Cyclophosphamide

1RG-CART/m\^2

To Determine Recommended Phase II Regimen by Assessing the Number of DLTs at Each Dose Level

All eligible patients who received 1RG-CART and provided at least one post-treatment blood sample taken on or after Day 14 for 1RG-CART analysis.

1RG-CART Counts in the Peripheral Blood

Best Response (RECIST) stable disease (SD)

Best Response (RECIST) progressive disease (PD)

All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.

Assessment of Tumour Response From Baseline (RECIST)

Best Response (irRC) stable disease (irSD)

Best Response (irRC) progressive disease (irPD)

Best Response (irRC) not evaluable (NE)

All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to Immune Related Response Criteria (irRC).

Assessment of Tumour Response From Baseline (irRC)

f the required level of 1RG-CART survival is not reached, a further cohort of patients (Dose Level 5) will receive 300 mg/m\^2/day of cyclophosphamide for four days (Days -7 to -4) and 25 mg/m\^2/day of fludarabine for five days (Days -8 to -4), followed by 5-10x10\^8 1RG-CART/m\^2 IV which could be be split over two days (Day 0 and Day 1).

Assigned Interventions:

Leukapheresis

Cyclophosphamide

Fludarabine

1RG-CART/m\^2

All eligible patients who received at least one dose of 1RG-CART and had a baseline assessment of disease and at least one repeat disease assessment measured according to International Neuroblastoma Response Criteria (INRC).

Assessment of Tumour Response From Baseline (INRC)

All eligible patients who received 1RG-CART and completed a baseline assessment of disease and at least one repeat disease assessment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Evaluating the Efficacy and Safety With CAR-T for Relapsed or Refractory Neuroblastoma in Children	NCT02919046	Relapsed or Ref...	GD2-targeted CA...	1 Year - 14 Years	Sinobioway Cell Therapy Co., Ltd.
Study Evaluating the Efficacy and Safety With CAR-T for Relapsed or Refractory Neuroblastoma in Children	NCT02919046	Relapsed or Ref...	GD2-targeted CA...	1 Year - 14 Years	Sinobioway Cell Therapy Co., Ltd.
A Phase I Trial of Anti-GD2 T-cells (1RG-CART)	NCT02761915	Relapsed or Ref...	Leukapheresis Cyclophosphamid... Fludarabine 1RG-CART	1 Year -	Cancer Research UK

Spots Global Cancer Trial Database for relapsed or refractory neuroblastoma