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

Primary Purpose

Relapsed or Refractory Neuroblastoma

Status

Unknown status

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

GD2-targeted CAR-T cells

About this trial

This is an interventional treatment trial for Relapsed or Refractory Neuroblastoma focused on measuring neuroblastoma, CAR-T

Eligibility Criteria

1 Year - 14 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Up to diagnostic criteria for relapsed or refractory neuroblastoma or high-risk patients，including:
- Relapsed neuroblastoma : Children diagnosed with neuroblastoma who after standard treatment and remission, present lesions again and cannot reach complete remission with surgery.
- Refractory neuroblastoma : ① Untreated patients that do not have to reach completes remission after 4 courses of chemotherapy in accordance with standard regimens nor reach complete remission with surgery. ② High-risk patients : Who have cell genetic variation, such as MYCN amplification or bone marrow metastasis.
Relapsed or Refractory Neuroblastoma: Target, of which expression may be intervened , discovered with Immunohistochemistry can be selected (GD2 +) (more than 50% of tumor cells is at least 2+ , adopting anti-GD2-mAb14G2a ).
Age: 1~14 years old of age at the time of enrollment, male or female.
Physical condition is good: ECOG score reaches 0 to 2 points.
Body weights greater than or equal to 10 kg.
White blood cell counts acuity≥ 1.0 x10^9 / L.
Estimated survival times > 90 days.
Voluntary participation, good compliance, can cooperate with the experimental observation and signed an informed consent form.

Exclusion Criteria:

Positive pregnancy tests.
Uncontrolled infection.
HIV infection, hepatitis B or C activity period.
Patients who need long-term immunosuppressive therapy (Such as allergies, autoimmune diseases, GVHD, etc.)
Combined activity of the central nervous system malignant tumor invasion.
Abnormal coagulation function, patients with severe thrombosis.
Organ failure
1. Heart：class Ⅱ or above.
2. Liver：class Ⅱ or above( Refer to Classification of Wuhan Conference (1983)).
3. Kidney: The second stage of renal insufficiency or above.
4. Lung: class Ⅱdecreased slightly or above.
5. Brain: The central nervous system transfer or have active lesions.
Patients who have participated in other clinical trials or other clinical trials in the past 30 days.
The researchers believe that the patient is not suitable to participate in the study.

Sites / Locations

Nanjing Children's HospitalRecruiting
Children's Hospital of Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single arm

Arm Description

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

Outcomes

Primary Outcome Measures

The overall efficiency of patients with neuroblastoma after autologous CAR-T cell therapy

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.

Secondary Outcome Measures

Progression free survival

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

Overall survival

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

Patients-based Quality of Life Evaluation

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.

3°or above incidence rate of serious adverse reaction related to treatment

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

Full Information

NCT ID

NCT02919046

First Posted

September 26, 2016

Last Updated

March 13, 2017

Sponsor

Sinobioway Cell Therapy Co., Ltd.

Collaborators

Nanjing Children's Hospital, Children's Hospital of Fudan University

1. Study Identification

Unique Protocol Identification Number

NCT02919046

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Unknown status

Study Start Date

September 2016 (undefined)

Primary Completion Date

September 2020 (Anticipated)

Study Completion Date

September 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sinobioway Cell Therapy Co., Ltd.

Collaborators

Nanjing Children's Hospital, Children's Hospital of Fudan University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsed or Refractory Neuroblastoma

Keywords

neuroblastoma, CAR-T

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

single arm

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

GD2-targeted CAR-T cells

Intervention Description

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.

Primary Outcome Measure Information:

Title

The overall efficiency of patients with neuroblastoma after autologous CAR-T cell therapy

Description

Time Frame

28d,56d,90d

Secondary Outcome Measure Information:

Title

Progression free survival

Description

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

Time Frame

3 years

Title

Overall survival

Description

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

Time Frame

3 years

Title

Patients-based Quality of Life Evaluation

Description

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.

Time Frame

3 years

Title

3°or above incidence rate of serious adverse reaction related to treatment

Description

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

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Up to diagnostic criteria for relapsed or refractory neuroblastoma or high-risk patients，including: Relapsed neuroblastoma : Children diagnosed with neuroblastoma who after standard treatment and remission, present lesions again and cannot reach complete remission with surgery. Refractory neuroblastoma : ① Untreated patients that do not have to reach completes remission after 4 courses of chemotherapy in accordance with standard regimens nor reach complete remission with surgery. ② High-risk patients : Who have cell genetic variation, such as MYCN amplification or bone marrow metastasis. Relapsed or Refractory Neuroblastoma: Target, of which expression may be intervened , discovered with Immunohistochemistry can be selected (GD2 +) (more than 50% of tumor cells is at least 2+ , adopting anti-GD2-mAb14G2a ). Age: 1~14 years old of age at the time of enrollment, male or female. Physical condition is good: ECOG score reaches 0 to 2 points. Body weights greater than or equal to 10 kg. White blood cell counts acuity≥ 1.0 x10^9 / L. Estimated survival times > 90 days. Voluntary participation, good compliance, can cooperate with the experimental observation and signed an informed consent form. Exclusion Criteria: Positive pregnancy tests. Uncontrolled infection. HIV infection, hepatitis B or C activity period. Patients who need long-term immunosuppressive therapy (Such as allergies, autoimmune diseases, GVHD, etc.) Combined activity of the central nervous system malignant tumor invasion. Abnormal coagulation function, patients with severe thrombosis. Organ failure Heart：class Ⅱ or above. Liver：class Ⅱ or above( Refer to Classification of Wuhan Conference (1983)). Kidney: The second stage of renal insufficiency or above. Lung: class Ⅱdecreased slightly or above. Brain: The central nervous system transfer or have active lesions. Patients who have participated in other clinical trials or other clinical trials in the past 30 days. The researchers believe that the patient is not suitable to participate in the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yongjun Fang, Ph.D

Phone

18951769586

fyj322@189.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yongjun Fang, Ph.D

Organizational Affiliation

Nanjing Children's Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Kuiran Dong, Ph.D

Organizational Affiliation

Children's Hospital of Fudan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nanjing Children's Hospital

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210008

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yongjun Fang, Ph.D

Phone

18951769586

fyj322@189.cn

First Name & Middle Initial & Last Name & Degree

Yongjun Fang, Ph.D

Facility Name

Children's Hospital of Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

201102

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kuiran Dong, Ph.D

Phone

18017591156

kuirand@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

27030986

Citation

Thomas S, Straathof K, Himoudi N, Anderson J, Pule M. An Optimized GD2-Targeting Retroviral Cassette for More Potent and Safer Cellular Therapy of Neuroblastoma and Other Cancers. PLoS One. 2016 Mar 31;11(3):e0152196. doi: 10.1371/journal.pone.0152196. eCollection 2016.

Results Reference

background

Links:

URL

http://dx.doi.org/10.1371/journal.pone.0152196

Description

An Optimized GD2-Targeting Retroviral Cassette for More Potent and Safer Cellular Therapy of Neuroblastoma and Other Cancers

Learn more about this trial

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

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