CMV-specific Cytotoxic T Lymphocytes Expressing CAR Targeting HER2 in Patients With GBM

Completed · Phase 1

Conditions studied: Glioblastoma Multiforme (GBM)

In brief

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.

Key facts

Study ID: NCT01109095
Run by: Baylor College of Medicine
People needed: 16
Starts: 2010-10-01
Expected to finish: 2018-03-07
Last updated by the study team: 2019-04-25

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

Severe intercurrent infection
Known HIV positivity
Pregnant or lactating
History of hypersensitivity reactions to murine protein-containing products

Where it is running

Houston Methodist Hospital — Houston, Texas, United States
Texas Children's Hospital — Houston, Texas, United States

Full record on ClinicalTrials.gov

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