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Trial record 1 of 46 for: chimera antigen
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3rd Generation GD-2 Chimeric Antigen Receptor and iCaspase Suicide Safety Switch, Neuroblastoma, GRAIN
This study is not yet open for participant recruitment.
Verified March 2013 by Baylor College of Medicine
Sponsor:
Baylor College of Medicine
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Information provided by (Responsible Party):
Chrystal Louis, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01822652
First received: March 28, 2013
Last updated: NA
Last verified: March 2013
History: No changes posted
Full Text View Tabular ViewNo Study Results PostedDisclaimerHow to Read a Study Record
Purpose
Subjects that have relapsed or refractory neuroblastoma are invited to take part in this gene transfer research study.
We have found from previous research that we can put a new gene called a chimeric antigen receptor (CAR) into T cells that will make them recognize neuroblastoma cells and kill them. In a previous clinical trial, we used a CAR that recognizes GD2, a protein found on almost all neuroblastoma cells (GD2-CAR). We put this gene into T cells and gave them back to patients that had neuroblastoma. The infusions were safe and in patients with disease at the time of their infusion, the time to progression was longer if we could find GD2 T cells in their blood for more than 6 weeks. Because of this, we think that if T cells are able to last longer, they may have a better chance of killing neuroblastoma tumor cells.
Therefore, in this study we will add new genes to the GD2 T cells that can cause the cells to live longer. These new genes are called CD28 and OX40. As a safety precaution we will also include another gene that can be activated to destroy the T cells in case there are unexpected or unwanted side effects. This "safety gene" is called iC9 and is turned on by a medication called AP1903.
The purpose of this study will be to determine the highest dose of iC9-GD2-CD28-OX40 (iC9-GD2) T cells that can safely be given to patients with relapsed/refractory neuroblastoma.
Condition Intervention Phase
Neuroblastoma
Genetic: iC9-GD2 T Cell Lymphocytes
Drug: AP1903
Phase 1
Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: AUTOLOGOUS ACTIVATED T-CELLS TRANSDUCED WITH A 3rd GENERATION GD-2 CHIMERIC ANTIGEN RECEPTOR AND iCASPASE9 SAFETY SWITCH ADMINISTERED TO PATIENTS WITH RELAPSED OR REFRACTORY NEUROBLASTOMA (GRAIN)
Resource links provided by NLM:
Genetics Home Reference related topics: neuroblastoma
MedlinePlus related topics: Cancer Neuroblastoma
U.S. FDA Resources
Further study details as provided by Baylor College of Medicine:
Primary Outcome Measures:
Dose limiting toxicities at 6 weeks post T cell infusion [ Time Frame: 6 weeks after infusion of the last dose of iC9-GD2 T cells to all patients on the study ] [ Designated as safety issue: Yes ]
We will measure and assess the adverse events to find the maximum tolerated dose of iC9-GD2 T cells and the safety profile of iC9-GD2 T cells.
Effects of AP1903 administration [ Time Frame: 6 weeks after infusion of the last dose of iC9-GD2 T cells to all patients on the study ] [ Designated as safety issue: Yes ]
Blood will be evaluated to measure the effect of T cell elimination after administration of the dimerizing drug.
Secondary Outcome Measures:
To evaluate the expansion and persistence of 3rd generation iC9-GD2 T cells [ Time Frame: 15 years ] [ Designated as safety issue: No ]
We will determine the expansion and functional persistence of iC9-GD2 T cells in the peripheral blood of patients using transgene detection by quantitative real-time PCR and response of transgenic cells to tumor antigen and to dimerizing drug in vitro.
Time to progression of disease [ Time Frame: 15 years ] [ Designated as safety issue: No ]
To describe the overall response rate and disease-free survival.
Change in serum cytokine and chemokine levels [ Time Frame: 15 years ] [ Designated as safety issue: No ]
The changes in patients' serum cytokine and chemokine levels after iC9-GD2 T cell infusion
Estimated Enrollment: 14
Study Start Date: May 2013
Estimated Study Completion Date: May 2030
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: iC9-GD2 T Cell Lymphocytes
The iC9-GD2 transduced T cells will given IV over 5-10 minutes. There is a possibility for additional doses of iC9-GD2 T cells.
Genetic: iC9-GD2 T Cell Lymphocytes
Subjects will receive the iC9-GD2 T cells through an IV over 5 to 10 minutes. Subjects will receive one of the following dose levels (cells/m2):
Dose Level 1 = 1 x 10^7
Dose Level 2 = 1 x 10^8
Dose Level 3 = 2 x 10^8
Six weeks after the infusion, patients will have a disease re-evaluation. If the disease has not gotten worse AND they have not had a severe side effect caused by the infusion of the iC9-GD2 T cells, the subject may be eligible to receive up to 2 additional doses of T cells. Each dose will be at the same dose level as the first infusion, if available, and separated by at least 6 weeks.
Other Names:
gene transfer
chimeric antigen receptor
CD28
OX40
Drug: AP1903
If there is development of Grade 3 or greater toxicity attributed to the infusion of iC9-GD2 T cells, we will administer a single dose of dimerizer drug (0.4mg/Kg I.V.) and measure the effects on circulating gene modified T cells and the associated toxicity.
Detailed Description:
We will make iC9-GD2 T cells by infecting normal T cells with a retroviral vector containing the iC9-GD2 gene. After the new gene has been put into the T cells, the cells will be tested to make sure that they kill GD2-positive neuroblastoma cells and then frozen until the patient is ready for their infusion.
The infusion will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital in Houston, Texas. The injection will take between 5 and 10 minutes, but patients should expect to remain in Houston for the first few weeks after the infusion just in case we need to give AP1903 to turn on the safety switch within the cells.
There will be follow-up visits every 1-2 weeks during the first 2 months and then they will be spaced out over a total of 15 years. Because the cells are modified with a new gene we must follow patients for at least 15 years to see if there are any long term side effects of gene transfer. During the visits, we will see how the patients are doing and during certain time points we will obtain extra blood samples to learn more about the way the iC9-GD2 T cells are working and how long they last in the body.
Eligibility
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
PROCUREMENT
High risk neuroblastoma with persistent or relapsed disease
Life expectancy of at least 12 weeks
Karnofsky/Lansky score of 60% or greater
Absence of HAMA prior to enrollment (only in patients that have been previously treated with murine antibodies)
Informed consent and assent (as applicable) obtained from parent/guardian and child
TREATMENT:
High risk neuroblastoma with persistent or relapsed disease
Life expectancy of at least 12 weeks
Karnofsky/Lansky score of 60% or greater
Patients must have an ANC greater than or equal to 500, platelet count greater than or equal to 20,000
Pulse Ox greater than or equal to 90% on room air
AST less than 5 times the upper limit of normal
Bilirubin less than 3 times the upper limit of normal
Serum creatinine less than 3 times upper limit of normal
Recovered from the toxic effects of all prior chemotherapy
Absence of human anti-mouse antibodies (HAMA) prior to enrollment for patients who have received prior therapy with murine antibodies
Patients must have autologous transduced activated T-cells with greater than or equal to 20% expression of GD2
Informed consent and assent (as applicable) obtained from parent/guardian and child
Exclusion Criteria:
PROCUREMENT:
Rapidly progressive disease
History of hypersensitivity to murine protein containing products
TREATMENT:
Rapidly progressive disease
Currently receiving other investigational drugs
History of hypersensitivity to murine protein containing products
History of cardiomegaly or bilateral pulmonary infiltrates on chest radiograph or CT
Evidence of tumor potentially causing airway obstruction
Patients who are pregnant, lactating, or unwilling to use birth control
Patients currently receiving immunosuppressive drugs such as corticosteroids, tacrolimus or cyclosporine
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01822652
Contacts
Contact: Brooke Straub 832-824-1904 bxstraub@texaschildrens.org
Contact: Chrystal Louis, MD culouis@txch.org
Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Chrystal Louis, MD Baylor College of Medicine
More Information
No publications provided
Responsible Party: Chrystal Louis, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01822652 History of Changes
Other Study ID Numbers: H-31493 GRAIN, GRAIN
Study First Received: March 28, 2013
Last Updated: March 28, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Keywords provided by Baylor College of Medicine:
Neuroblastoma
Solid tumor
Neuroblastoma-specific immunotherapy targeting GD2
CAR T cells
Gene Therapy
Relapsed
Refractory
Additional relevant MeSH terms:
Neuroblastoma
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
ClinicalTrials.gov processed this record on July 04, 2013
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