Glioblastoma Multiforme (GBM) Clinical Trial
— HERT-GBMOfficial title:
Administration of HER2 Chimeric Antigen Receptor Expressing CMV-Specific Cytotoxic T Cells Ins Patients With Glioblastoma Multiforme (HERT-GBM)
Verified date | April 2019 |
Source | Baylor College of Medicine |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This study is for patients that have a type of brain cancer called glioblastoma multiforme
(GBM).
The body has different ways of fighting infection and disease. No single way seems perfect
for fighting cancers. This research study combines two different ways of fighting cancer:
antibodies and T cells. Antibodies are types of proteins that protect the body from
infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special
infection-fighting blood cells that can kill other cells, including cells infected with
viruses and tumor cells. Both antibodies and T cells have been used to treat patients with
cancers. They have shown promise, but have not been strong enough to cure most patients.
The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor
2). This antibody sticks to GBM cells because of a substance on the outside of these cells
called HER2. Up to 80% of GBMs are positive for HER2. HER2 antibodies have been used to treat
people with HER2-positive cancers. For this study, the HER2 antibody has been changed so that
instead of floating free in the blood it is now attached to T cells. When an antibody is
joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T
cells seem to be able to kill tumors like GBM, but they don't last very long and so their
chances of fighting the cancer are limited. Therefore, developing ways to prolong the life of
these T cells should help them fight cancer.
We found that T cells work better if we also attach a protein called CD28 to the HER2
chimeric receptor (HER2-CAR). In this study we placed this HER2-CAR into T cells that were
pre-selected for their ability to recognize Cytomegalovirus (CMV). This virus exists in most
people. These CMV-specific cytotoxic T cells (CMV-T cells) will be more active since they
will react to the virus as well as to tumor cells. These HER2-CD28 CMV-T cells are an
investigational product not approved by the Food and Drug Administration.
The purpose of this study is to find the largest safe dose of HER2-CD28 CMV-T cells, to learn
what the side effects are, and to see whether this therapy might help patients with GBM.
Status | Completed |
Enrollment | 16 |
Est. completion date | March 7, 2018 |
Est. primary completion date | June 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A and older |
Eligibility |
INCLUSION CRITERIA: - Histopathological verification of glioblastoma multiforme (GBM: WHO grade IV) with recurrent or progressive disease after front line therapy. - HER2 positive GBM - CMV seropositive - Normal ECHO (Left ventricular ejection fraction (LVEF) has to be with in normal, institutional limits) - Life expectancy 6 weeks or greater - Karnofsky/Lansky score 50 or greater - Patient or parent/guardian capable of providing informed consent - Bilirubin 3x or less than normal, AST 5x or less than normal, creatinine 2x normal or less for age and Hgb 9.0 g/dl or more; WBC greater than 2,000/ul; ANC greater than 1,000/ul; platelets greater than 100,000/ul - Pulse oximetry 90% or more on room air - Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. The male partner should use a condom. - Available autologous HER2.CAR-transduced CMV-specific cytotoxic T lymphocytes with 15% or greater expression of HER2.CAR determined by flow-cytometry and killing of HER2-positive targets 20% or more in cytotoxicity assay. - Recovered from the acute toxic effects of all prior chemotherapy at least 4 weeks before entering this study. One exception is Temozolomide(TMZ), an alkylation agent used as a radiosensitizer and adjuvant chemotherapeutic agent for GBM. Due to the extremely short half life of TMZ, patients will be allowed to continue receiving it up to two days prior to cell infusion and cannot restart until six weeks after the infusion. EXCLUSION CRITERIA: - Severe intercurrent infection - Known HIV positivity - Pregnant or lactating - History of hypersensitivity reactions to murine protein-containing products |
Country | Name | City | State |
---|---|---|---|
United States | Houston Methodist Hospital | Houston | Texas |
United States | Texas Children's Hospital | Houston | Texas |
Lead Sponsor | Collaborator |
---|---|
Baylor College of Medicine | Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital System |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of subjects with dose limiting toxicity after CTL infusion | To evaluate the safety of escalating doses of autologous CMV-specific cytotoxic T-lymphocytes (CTL) genetically modified to express chimeric antigen receptors (CAR) targeting the HER2 molecule in patients with HER2-positive Glioblastoma multiforme (GBM: WHO grade IV), who have recurrent or progressive disease after front line therapy. | 6 weeks | |
Secondary | Decrease in tumor after the CTL infusion | To evaluate the effects of gene modified CTL on measurable disease. | 6 weeks | |
Secondary | Area under the growth curves (AUC) over time for T cell frequencies. | To measure the survival and function of gene modified CTL in vivo. | 15 years | |
Secondary | Impact of gene modified CTL on CMV-specific T lymphocyte immune response | Immune function assays including ELISPOT or CTLp assays and cytotoxicity assays to look at specificity of response will be done in patients on whom the appropriate reagents are available | 15 years |
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