Study on GD2 Positive Solid Tumors by 4SCAR-GD2

• ClinicalTrials.gov Identifier: NCT02992210
• Recruitment Status: Unknown
• First Posted: December 14, 2016
• Last Update Posted: February 19, 2018
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: December 3, 2016
• First Posted Date: December 14, 2016
• Last Update Posted Date: February 19, 2018
• Study Start Date: May 2016
• Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 13, 2016)

Number of patients with adverse events. [ Time Frame: 3 year ]

Determine the toxicity profile the 4SCAR-GD2-modified T cells with Common Toxicity Criteria for Adverse Effects version 4.0

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 13, 2016)

• Anti-tumor effects [ Time Frame: 3 year ]
  Disease status is defined by the biochemical markers and image scan to get the outcomes such as Complete response/remission (CR) , Very good partial response/remission (VGPR) , etc
• The expansion and persistence of anti-GD2 CAR T cells [ Time Frame: 3 year ]
  The 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
• Immune responses after anti-GD2 infusions [ Time Frame: 1 year ]
  assessment of lymphocyte phenotypes and anti-tumor activity
• Immune responses after anti-GD2 infusions [ Time Frame: 1 year ]
  assessment of cytokine profile
• Survival time of the patients [ Time Frame: 3 year ]
  Evaluate the survival time of the patients treated with the 4SCAR-GD2 T cells, including progression free survival (PFS) and overall survival (OS)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study on GD2 Positive Solid Tumors by 4SCAR-GD2
• Official Title: Multicenter Trial of Phase I/II Studies on GD2 Positive Solid Tumors by 4SCAR-GD2
• Brief Summary: Patients with refractory and/or recurrent solid tumor have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. The investigators are attempt to treat these diseases using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (4SCAR fused with an inducible apoptotic caspase 9 domain) targeting GD2 (4SCAR-GD2). The 4SCAR-GD2-modified T cells can recognize and kill tumor cells through the recognition of GD2, a surface protein expressed at high levels on many types of tumors 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 tumors.

Detailed Description

Background:

Patients with refractory and/or recurrent solid tumors 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 tumor cells through the recognition of a surface antigen, GD2, which is expressed at high levels on tumor cells 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 solid tumors.

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 -5 to -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 5-7 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 will be based on patient immune condition and consistent with standard chemotherapy conditioning regimen.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

Genetic: 4SCAR-GD2

Other Name: GD2-specific 4th Generation CART

Study Arms

Experimental: effectiveness of 4SCAR-GD2 T cells

The 4SCAR-GD2-modified T cells can recognize and kill tumor cells through the recognize of GD2 .This study will evaluate the side effects and effective doses of 4SCAR-GD2 T cells in treating refractory and recurrent solid tumors

Intervention: Genetic: 4SCAR-GD2

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 13, 2016): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients with tumors have received standard first-line therapy and been judged to be non-resectable，metastatic,progressive or recurrent.
• The GD2 antigen status of the tumor 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 ≤ 65 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.
• For all patients enrolled in this study, their parents or legal guardians must sign an informed consent and assent.

Exclusion Criteria:

• 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.
• Evidence of tumor potentially causing airway obstruction.
• Inability to comply with protocol requirements.
• Insufficient CAR T cells availability.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02992210
• Other Study ID Numbers: GIMI-IRB-16002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lung-Ji Chang; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: February 2018