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Administration of CMV-Specific Cytotoxic T Cells in Patients With Glioblastoma Multiforme

Phase 1
Terminated
Conditions
Glioblastoma Multiforme
GBM
Brain Cancer
Interventions
Biological: Autologous CMV-specific CTL
Registration Number
NCT01205334
Lead Sponsor
Baylor College of Medicine
Brief Summary

Patients have a type of brain cancer called glioblastoma multiforme. Because most GBMs come back after standard therapy, patients are being asked to volunteer to take part in a research study using special immune cells. They may have already thought about being in this study.

Some patients with GBM show evidence of infection with a virus called Cytomegalovirus before the time of their diagnosis. CMV is found in the cancer cells of some patients with GBM, suggesting that it may play a role in causing the disease. The cancer cells infected by CMV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells, called T cells, that have been trained to recognize and kill special parts of CMV infected cells can survive in the blood and affect the tumor.

We have used this sort of therapy to treat different types of cancer that are positive for other viruses and have had variable results. Some patients have had responses others did not. It is not possible for us to predict if this treatment will work for GBM.

The purpose of this study is to find the largest safe dose of CMV-T cells, to learn what the side effects are, and to see whether this therapy might help patients with GBM.

Detailed Description

To generate CMV-T cells we put a specially produced carrier virus (adenovirus) that carries one CMV gene into the patient's blood monocytes or dendritic cells. These cells are then used to train the patient's T cells to kill cells with CMV on their surface. We then grow these CMV-T cells by more stimulations with Epstein-Barr virus (EBV)infected cells from the patient's blood, which also contain the adenovirus with the CMV gene.

When the patient enrolls on this study, they will be assigned a dose of CMV-T cells.

The patient will be given an injection of cells into the vein through an IV line at the assigned dose. The patient will be followed in the clinic after the injection for 1 to 4 hours.

If after a 6 week evaluation period after the infusion, the patient seems to be experiencing a benefit (tumor regression confirmed by radiological studies, physical exam and/or symptoms), they may be able to receive up to six additional doses of the T cells if they wish. These additional infusions would be at least 1 to 3 months apart and at the same dose level they received the first time.

Medical tests before treatment--

Before being treated, the patient will receive a series of standard medical tests: Physical exam, Pregnancy test (if applicable), Blood tests to measure blood cells, kidney and liver function, Measurements of your tumor by routine imaging studies

Medical tests during and after treatment--

The patient will receive standard medical tests when getting the infusions and after: Physical exams, Blood tests to measure blood cells, kidney and liver function, Measurements of your tumor by routine imaging studies 6 weeks after the infusion

To learn more about the way the CMV-T cells are working and how long they last in the body, blood will be taken on the day of the T-cell infusion, before and at the end of the T-cell infusion, 1, 2, 4 and 6 weeks after the T-cell infusion and every 3 months for 1 year.

Total time participation for this study will be 1 year.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Autologous CMV-specific CTLAutologous CMV-specific CTLThe patient will receive one of the following doses: * 1.5x10\^7 cells/m2 * 4.5x10\^7 cells/m2 * 1.5x10\^8 cells/m2
Primary Outcome Measures
NameTimeMethod
Number of subjects with dose limiting toxicity6 weeks

The main aim will be to collect information about the maximum tolerated dosage to evaluate the safety of escalating doses of autologous CMV-specific cytotoxic T-lymphocytes (CTL) in patients with CMV-positive Glioblastoma multiforme (GBM)

Secondary Outcome Measures
NameTimeMethod
Area under the growth curves (AUC) over time for T cell frequencies1 year

To measure the survival and function of CMV-specific CTL in vivo.

Patients with a decrease in disease after the CTL infusion6 weeks

To evaluate the effects of CMV-specific CTL on measurable disease.

Trial Locations

Locations (2)

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

The Methodist Hospital

🇺🇸

Houston, Texas, United States

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