Glioblastoma Multiforme (GBM)Phase 1HERT-GBMNCT01109095
CMV-specific Cytotoxic T Lymphocytes Expressing CAR Targeting HER2 in Patients With GBM
A Phase 1 study testing HER.CAR CMV-specific CTLs in people with Glioblastoma Multiforme (GBM), run by Baylor College of Medicine at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Glioblastoma Multiforme (GBM)
- What is being tested?
- HER.CAR CMV-specific CTLs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2010to 7 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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.
Who cannot join
- Severe intercurrent infection
- Known HIV positivity
- Pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Houston Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: Administration of HER2 Chimeric Antigen Receptor Expressing CMV-Specific Cytotoxic T Cells Ins Patients With Glioblastoma Multiforme (HERT-GBM)
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.
Read more
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.
Read the detailed description
When the patient enrolls on this study, they will be assigned to a dose of HER2-CAR CMV-T cells.
The patient will be given a single injection of cells into the vein through an IV line at the assigned dose. The injection will take between 1 and 10 minutes. The patient will be followed in the clinic after the injection for 1 to 4 hours. If later the subject seems to be experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms), s/he may be able to receive up to six additional doses of the T cells if they wish. These additional infusions would be at least 6 to 12 weeks apart and at the same dose level received the first time.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests as follows: Physical exam, Blood tests to measure blood cells, kidney and liver function, Routine heart function tests (Echocardiogram),Measurements of the 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, Routine heart function tests (Echocardiogram) at 6 weeks after the infusion, Measurements of the tumor by routine imaging studies 6 weeks after the infusion
To learn more about the way the HER2-CAR 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, 1 hour and 4 hours after the T-cell infusion, 1, 2, 4 and 6 weeks after the T-cell infusion and every 3 months for 1 year, every 6 months for 4 years, then yearly for a total of 15 years.
- Conditions
- Glioblastoma Multiforme (GBM)
- Being tested
- HER.CAR CMV-specific CTLs
- Keywords
- Glioblastoma Multiforme (GBM), HER2, CMV, Brain Cancer, Autologous HER2.CAR CMV-specific cytotoxic CTL, CMV-specific cytotoxic CTL
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HER.CAR CMV-specific CTLsBiological
HER2.CAR CMV-specific CTLs will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line with a minimum 20g cannula. The patient will get one of the following doses:
- 1 x 10^6/m^2
- 3 x 10^6/m^2
- 1 x 10^7/m^2
- 3 x 10^7/m^2
- 1 x 10^8/m^2
| Study group | Role | What they receive |
|---|---|---|
| HER.CAR CMV-specific CTLs | Experimental | Subject will be assigned a dose level at study entry. Receives: Biological: HER.CAR CMV-specific CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Secondary outcomes (3)
Decrease in tumor after the CTL infusion
To evaluate the effects of gene modified CTL on measurable disease.
Measured: 6 weeks
Area under the growth curves (AUC) over time for T cell frequencies.
To measure the survival and function of gene modified CTL in vivo.
Measured: 15 years
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
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2014
- Study completion7 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma Multiforme (GBM)Studies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Nabil Ahmed, Baylor College of Medicine
- Investigators
- Nabil Ahmed, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01109095
- Sponsor's protocol ID
- H-24487 - HERT GBM
- Acronym
- HERT-GBM
- Status last verified
- Apr 2019
- First submitted
- 13 Apr 2010
- Last updated
- 25 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Badhiwala J, Decker WK, Berens ME, Bhardwaj RD. Clinical trials in cellular immunotherapy for brain/CNS tumors. Expert Rev Neurother. 2013 Apr;13(4):405-24. doi: 10.1586/ern.13.23.
PubMed 23545055
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of HER2 Chimeric Antigen Receptor Expressing CMV-Specific Cytotoxic T Cells Ins Patients With Glioblastoma Multiforme (HERT-GBM)
- ClinicalTrials.gov ID
- NCT01109095
- Acronym / sponsor ID
- HERT-GBM / H-24487 - HERT GBM
- Conditions
- Glioblastoma Multiforme (GBM)
- Keywords
- Glioblastoma Multiforme (GBM), HER2, CMV, Brain Cancer, Autologous HER2.CAR CMV-specific cytotoxic CTL, CMV-specific cytotoxic CTL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Oct 2010
- Primary completion
- Jun 2014 (actual)
- Study completion
- 7 Mar 2018 (actual)
- First posted
- 22 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
When the patient enrolls on this study, they will be assigned to a dose of HER2-CAR CMV-T cells.
The patient will be given a single injection of cells into the vein through an IV line at the assigned dose. The injection will take between 1 and 10 minutes. The patient will be followed in the clinic after the injection for 1 to 4 hours. If later the subject seems to be experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms), s/he may be able to receive up to six additional doses of the T cells if they wish. These additional infusions would be at least 6 to 12 weeks apart and at the same dose level received the first time.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests as follows: Physical exam, Blood tests to measure blood cells, kidney and liver function, Routine heart function tests (Echocardiogram),Measurements of the 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, Routine heart function tests (Echocardiogram) at 6 weeks after the infusion, Measurements of the tumor by routine imaging studies 6 weeks after the infusion
To learn more about the way the HER2-CAR 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, 1 hour and 4 hours after the T-cell infusion, 1, 2, 4 and 6 weeks after the T-cell infusion and every 3 months for 1 year, every 6 months for 4 years, then yearly for a total of 15 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HER.CAR CMV-specific CTLs | Experimental | Biological: HER.CAR CMV-specific CTLsSubject will be assigned a dose level at study entry. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (4 listed)
- Severe intercurrent infection
- Known HIV positivity
- Pregnant or lactating
- History of hypersensitivity reactions to murine protein-containing products
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HER.CAR CMV-specific CTLsHER2.CAR CMV-specific CTLs will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line with a minimum 20g cannula. The patient will get one of the following doses: * 1 x 10^6/m^2 * 3 x 10^6/m^2 * 1 x 10^7/m^2 * 3 x 10^7/m^2 * 1 x 10^8/m^2 | Biological | HER.CAR CMV-specific CTLs |
Primary outcome
Number of subjects with dose limiting toxicity after CTL infusion
Time frame: 6 weeks
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.
3 secondary outcomes
Decrease in tumor after the CTL infusion
Time frame: 6 weeks
Area under the growth curves (AUC) over time for T cell frequencies.
Time frame: 15 years
Impact of gene modified CTL on CMV-specific T lymphocyte immune response
Time frame: 15 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2019.
- Derived from this study: PubMed 23545055Badhiwala J, Decker WK, Berens ME, Bhardwaj RD. Clinical trials in cellular immunotherapy for brain/CNS tumors. Expert Rev Neurother. 2013 Apr;13(4):405-24. doi: 10.1586/ern.13.23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nabil Ahmed, MD principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HER.CAR CMV-specific CTLs in people with Glioblastoma Multiforme (GBM), run by Baylor College of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with dose limiting toxicity after CTL infusion (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01109095, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2019.