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)
N/A
N/A
Both
Neuroblastoma
Trial Information
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)
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose limiting toxicities at 6 weeks post T cell infusion
Outcome Description:
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.
Outcome Time Frame:
6 weeks after infusion of the last dose of iC9-GD2 T cells to all patients on the study
Safety Issue:
Yes
Principal Investigator
Chrystal Louis, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Baylor College of Medicine
Authority:
United States: Food and Drug Administration
Study ID:
H-31493 GRAIN
NCT ID:
NCT01822652
Start Date:
May 2013
Completion Date:
May 2030
Related Keywords:
- Neuroblastoma
- Neuroblastoma
- Solid tumor
- Neuroblastoma-specific immunotherapy targeting GD2
- CAR T cells
- Gene Therapy
- Relapsed
- Refractory
- Neuroblastoma
Name | Location |
|---|---|
| Texas Children's Hospital | Houston, Texas |
