- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01205334
Administration of CMV-Specific Cytotoxic T Cells in Patients With Glioblastoma Multiforme (COGLI)
Phase I/II Administration of CMV (Cytomegalovirus)-Specific Cytotoxic T Cells in Patients With Glioblastoma Multiforme (COGLI)
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- The Methodist Hospital
-
Houston, Texas, United States, 77030
- Texas Children's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
INCLUSION CRITERIA:
- Histopathological verification of glioblastoma multiforme (GBM: WHO grade IV) in remission (Group A) or with active disease (Group B).
- CMV-positive GBM
- CMV seropositive
- Life expectancy 6 weeks or greater
- Karnofsky/Lansky score 50 or greater
- Patient or parent/guardian capable of providing informed consent
- Bilirubin less than 1.5x upper limit of normal, AST less than 3x upper limit of normal, serum creatinine less than 1.5x normal and Hgb 8.0 g/dL or greater
- Pulse oximetry of 90% or greater 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.
- Patients should have been off other investigational antineoplastic therapy for one month prior to entry in this study.
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
EXCLUSION CRITERIA:
- Severe intercurrent infection
- Known HIV positivity
- Pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Autologous CMV-specific CTL
The patient will receive one of the following doses:
|
CMV-specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line with a minimum 20g cannula. The expected volume will be 1-50 cc. At the discretion of the attending physician, subjects can receive repeat infusions of modified T cells at the same dose level as long as they do not have progressive disease (up to a maximum of 6 doses and the minimum interval between repeat infusions is 6 weeks). Infusion procedures and follow-up will be identical to those for the first infusion. Patients, who receive additional doses of CTLs will be monitored exactly like after the 1st CTL infusion.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of subjects with dose limiting toxicity
Time Frame: 6 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)
|
6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patients with a decrease in disease after the CTL infusion
Time Frame: 6 weeks
|
To evaluate the effects of CMV-specific CTL on measurable disease.
|
6 weeks
|
Area under the growth curves (AUC) over time for T cell frequencies
Time Frame: 1 year
|
To measure the survival and function of CMV-specific CTL in vivo.
|
1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Nabil M. Ahmed, MD, Center for Cell and Gene Therapy, Baylor College of Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Glioblastoma
- Brain Neoplasms
Other Study ID Numbers
- 26901-COGLI
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Brain Cancer
-
University of Michigan Rogel Cancer CenterRecruitingCancer Liver | Cancer Brain | Cancer Head &Neck | Cancer PelvisUnited States
-
Xinhua Hospital, Shanghai Jiao Tong University...UnknownCancer | Metastatic Cancer | Metastatic Brain CancerChina
-
University of FloridaCompletedBrain Neoplasms | Brain Cancer | Brain Tumors | Seizure | Cancer of the Brain | Cancer of BrainUnited States
-
Eisai Inc.CompletedMetastatic Brain CancerUnited States
-
Sunnybrook Health Sciences CentreActive, not recruitingBreast Cancer | Head and Neck Cancer | Gynecologic Cancer | Brain CancerCanada
-
Australian & New Zealand Children's Haematology...Medical Research Future Fund; Minderoo Foundation; Children's Cancer Institute...RecruitingChildhood Cancer | Relapsed Cancer | Refractory Cancer | Childhood Leukemia | Childhood Solid Tumor | Childhood Brain TumorAustralia
-
InSightecActive, not recruitingGlioma | Metastatic Brain CancerCanada
-
Virginia Commonwealth UniversityUnited States Department of DefenseActive, not recruitingBrain Metastases, Adult | Cancer Metastatic to BrainUnited States
-
Institut National de la Santé Et de la Recherche...RecruitingPediatric Cancer | Cancer BrainFrance
Clinical Trials on Autologous CMV-specific CTL
-
Nantes University HospitalTerminatedSerologically Active Adult Systemic Lupus ErythematosusFrance
-
Nantes University HospitalRecruiting
-
Baylor College of MedicineThe Methodist Hospital Research Institute; Center for Cell and Gene Therapy...Active, not recruitingHodgkin's Lymphoma | Non-Hodgkin's LymphomaUnited States
-
Baylor College of MedicineNational Heart, Lung, and Blood Institute (NHLBI); The Methodist Hospital Research... and other collaboratorsCompletedCytomegalovirus InfectionsUnited States
-
National Institute of Diabetes and Digestive and...CompletedLymphoproliferative Disorders | Liver DiseaseUnited States
-
Catherine BollardActive, not recruiting
-
City of Hope Medical CenterNational Cancer Institute (NCI)RecruitingDiffuse Large B-Cell Lymphoma | Recurrent Mantle Cell Lymphoma | Mantle Cell Lymphoma | B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Diffuse Large B-Cell Lymphoma | Recurrent Transformed Non-Hodgkin Lymphoma | Transformed Non-Hodgkin LymphomaUnited States
-
Shixiu WuUnknownDigestive System Diseases | Esophageal Neoplasms | Esophageal DiseasesChina
-
Affiliated Hospital to Academy of Military Medical...Unknown
-
Nantes University HospitalCompletedImmunotherapyFrance