Anti-GD2 4th Generation CART Cells Targeting Refractory and/or Recurrent Neuroblastoma

NCT02765243 | Completed Phase 1 DMC

• 1 other identifier: 2016-EKZX-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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) 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.

Conditions

Neuroblastoma; Effects of Immunotherapy

Keywords

neuroblastoma; GD2; Chimeric antigen receptor; Immunotherapy; Cyclophosphamide; Fludarabine

Outcome Measures

Primary Outcomes (1)

• 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.

  1yr

Secondary Outcomes (3)

• Anti-tumor effects

  1yr

• To evaluate the expansion and persistence of anti-GD2 CAR T cells

  1yr

• Survival time of the patients

  1yr

Study Arms (1)

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

Biological: Anti-GD2 CART

Interventions

Anti-GD2 CART BIOLOGICAL

Anti-GD2 4th Generation Chimeric Antigen Receptor-modified T Cells

effectiveness of Anti-GD2 CART

Eligibility Criteria

• Age: 1 Year - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Zhujiang Hospital: lead

Study Sites (1)

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510282, China

Location

MeSH Terms

Conditions

Neuroblastoma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Lihua Yang, M.D., Ph.D.

  Southern Medical University, China

  PRINCIPAL INVESTIGATOR

• Lung-Ji Chang, Ph.D.

  Shenzhen Genoimmune Medical Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director

Study Record Dates

• First Submitted: May 3, 2016
• First Posted: May 6, 2016
• Study Start: January 1, 2016
• Primary Completion: January 12, 2019
• Study Completion: December 30, 2023
• Last Updated: March 15, 2024

Record last verified: 2021-08

Locations

CN (1)