Clinical trial NCT02919046: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Relapsed or Refractory Neuroblastoma
Keywords: neuroblastoma
CAR-T
Lead sponsor: Sinobioway Cell Therapy Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Nanjing Children's Hospital
name: Children's Hospital of Fudan University
First posted: 2016-09-29
Enrollment: 22
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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 ).
3. Age: 1\~14 years old of age at the time of enrollment, male or female.
4. Physical condition is good: ECOG score reaches 0 to 2 points.
5. Body weights greater than or equal to 10 kg.
6. White blood cell counts acuity≥ 1.0 x10\^9 / L.
7. Estimated survival times \> 90 days.
8. Voluntary participation, good compliance, can cooperate with the experimental observation and signed an informed consent form.

Exclusion Criteria:

1. Positive pregnancy tests.
2. Uncontrolled infection.
3. HIV infection, hepatitis B or C activity period.
4. Patients who need long-term immunosuppressive therapy (Such as allergies, autoimmune diseases, GVHD, etc.)
5. Combined activity of the central nervous system malignant tumor invasion.
6. Abnormal coagulation function, patients with severe thrombosis.
7. 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.
8. Patients who have participated in other clinical trials or other clinical trials in the past 30 days.
9. The researchers believe that the patient is not suitable to participate in the study.

Primary outcomes:
measure: The overall efficiency of patients with neuroblastoma after autologous CAR-T cell therapy
timeFrame: 28d,56d,90d
Secondary outcomes:
measure: Progression free survival
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
measure: Patients-based Quality of Life Evaluation
timeFrame: 3 years
measure: 3°or above incidence rate of serious adverse reaction related to treatment
timeFrame: 3 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing Children's Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Nanjing Children's Hospital
name: Yongjun Fang, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Fudan University
name: Kuiran Dong, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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.