HER2 Positive MalignanciesPhase 1HERCREEMNCT00889954
Her2 and TGFBeta Cytotoxic T Cells in Treatment of Her2 Positive Malignancy
A Phase 1 study testing TGFBeta resistant HER2/EBV-CTLs in people with HER2 Positive Malignancies, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
Patients have advanced stage cancer. This study is a gene transfer research study using special immune cells. 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?
- Ages 3 years and older
- Conditions the study is for
- HER2 Positive Malignancies
- What is being tested?
- TGFBeta resistant HER2/EBV-CTLs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2009to 21 Jan 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 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The patient must meet the following eligibility inclusion criteria at the time of PROCUREMENT:
- Diagnosis of advanced stage* or metastatic HER2-positive cancer (Immunohistochemistry or reverse transcription-polymerase chain reaction (RT-PCR) is used to determine HER2 positivity)
- Definitions of Malignancies and Advanced Stages:
- Breast ≥Stage IIIb Colon cancer ≥Stage IIIb Esophageal cancer ≥Stage IIIb Gastric carcinoma ≥Stage IIIb Head and Neck cancer Stage IV Lung cancer ≥Stage IIIb Pancreatic cancer Stage IV Prostate cancer Stage IV
- it is expected that the majority of patients who will be accrued on the protocol will have one of the HER2-positive malignancies listed in the table. If the patient's malignancy is not listed we will use ≥ Stage IIIb as the definition of advanced stage disease. If Stage IIIb is not part of the staging system for the individual tumor, Stage IV will be used.
- For World Health Organization grade III and IV brain tumors):patients will be eligible, who have recurrent or progressive disease after front line therapy.
Show all 24Show fewer
- Karnofsky/Lansky score of 50 or more
- EBV seropositive
- Greater than or equal to 3 years old
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
- The patient must meet the following eligibility criteria to be included for TREATMENT:
- Diagnosis of advanced stage* or metastatic HER2-positive cancer with disease progressed after receiving at least one prior systemic therapy. (Immunohistochemistry or RT-PCR is used to determine HER2 positivity) *for definition refer to Table above.
- Greater than or equal to 3 years old.
- EBV-seropositive
- Recovered from the acute toxic effects of all prior chemotherapy at least a week before entering this study.
- Normal echocardiogram (Left ventricular ejection fraction (LVEF) has to be with in normal, institutional limits)
- 5. Life expectancy 6 weeks or more
- 7. Karnofsky/Lansky score of 50 or more
- 8. Bilirubin 3x or less, Aspartate aminotransferase (AST) 5x or less, Serum creatinine 2x or less upper limit of normal, Hgb 9.0 g/dl or more, white blood cells greater than 2,000/ul, absolute neutrophil count greater than 1,000/ul, Platelets greater than 100,000/ul
- 9. Pulse oximetry 90% or more on room air
- 10. Sexually active patients must be willing to utilize one of the more effective birth control methods for 6 months after the CTL infusion. Male partner should use a condom. Acceptable forms of birth control include: oral contraceptives ("the pill"), intrauterine devices (IUDs), contraceptive implants under the skin, or contraceptive injections, condoms with foam.
- 11. Available autologous transduced EBV-specific cytotoxic T lymphocytes with 15% or more expression of HER2 CAR determined by flow-cytometry and killing of Her2-positive targets 20% or more in cytotoxicity assay.
- 12. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
- Note: Patients must also not receive antineoplastic drugs while on this study since they would kill the infused T cells.
Who cannot join
- At time of Procurement:
- 1. Known HIV positivity
- At time of Treatment:
- 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 Receptor and TGFbeta Dominant Negative Receptor (DNR) Expressing EBV Specific Lymphocytes for Subjects With Advanced Her2 Positive Malignancy (HERCREEM)
Patients have advanced stage cancer. This study is a gene transfer research study using special immune cells.
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. Investigators hope that both will work better together. Antibodies are proteins that protect the body from diseases caused from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients.
Read more
T lymphocytes can kill tumor cells but there are normally not enough of them or they are not able to kill all the tumor cells. We have done research in which we have grown "extra" T lymphocytes. We have added genes to those T lymphocytes to help them to recognize tumor cells. Although the results have been promising, we are still doing more research in this area.
Antibodies usually circulate in blood and are secreted by other cells of the immune system in response to the presence of germs or abnormal cells in the body. The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to HER2-positive cancer cells because of a substance on the outside of these cells called HER2.
Read the detailed description
The patient will give blood to grow T cells on either one to two separate occasions. Then, the EBV-specific T cells will be made. These cells will be grown and frozen. To get the HER2 antibody (and the CD28) and the DNR to attach to the surface of the EBV-T cells, the antibody gene and the DNR gene will be inserted into the EBV-T cell. This is done with two viruses called retroviruses that have been made for this study. One will carry the antibody gene into the T cell and the other the DNR gene.
When the patient is enrolled on the study, they will be assigned to a dose of HER2-DNR EBV-T cells. The subject will be given one dose of cells into the vein through an IV line. 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. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
- Conditions
- HER2 Positive Malignancies
- Being tested
- TGFBeta resistant HER2/EBV-CTLs
- Keywords
- EBV+, Her2, TGFBeta, EBV positive, HER 2 positive malignancy, cytotoxic T lymphocytes
- Medical subject headings
- Camurati-Engelmann Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TGFBeta resistant HER2/EBV-CTLsBiological
Also called HER2-DNR EBV T cells
Each patient will receive one injection of the TGFBeta resistant HER2/EBV-specific CTLs. Each pt will be followed for 6 weeks after the CTL infusion for evaluation of dose limiting toxicity (DLT).
Patients may receive up to six additional doses of the T cells at 6 to 12 weeks intervals.
| Study group | Role | What they receive |
|---|---|---|
| TGFBeta resistant HER2/EBV-CTLs | Experimental | The following dose levels will be evaluated:
Dose Level 1: 1 x 10^4 cells/m^2
Dose Level 2: 3 x 10^4 cells/m^2
Dose Level 5: 1 x 10^6 cells/m^2
Dose Level 6: 3 x 10^6 cells/m^2
Dose Level 7: 1 x 10^7 cells/m^2
Dose Level 8: 3 x 10^7 cells/m^2
Dose Level 9:1 x 10^8 cells/m^2 Receives: Biological: TGFBeta resistant HER2/EBV-CTLs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients with dose limiting toxicity.
Determine safety of one IV injection of autologous TGFBeta-resistant cytotoxic T cells (CTL) directed to Epstein Barr virus (EBV) through their native receptor and HER2 through their chimeric antigen receptor (CAR) in patients with advanced HER2- positive cancers.
Measured: 6 weeks
Secondary outcomes (2)
Area under the growth curves (AUC) over time for T cell frequencies.
To compare the survival and the immune function of the TGFBeta-resistant and non resistant components of the infused CAR-CTL.
Measured: 15 years
Decrease in tumor after the CTL infusion
To assess the anti-tumor effects of the infused CAR-CTL.
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 posted29 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionJul 2015
- Study completion21 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2 Positive MalignanciesStudies 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
- 20 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, Stephen Gottschalk, Baylor College of Medicine
- Investigators
- Stepehen Gottschalk, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00889954
- Sponsor's protocol ID
- 24486-HERCREEM
- Other IDs
- HERCREEM
- Acronym
- HERCREEM
- Status last verified
- Sep 2018
- First submitted
- 24 Apr 2009
- Last updated
- 18 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Her2 Chimeric Receptor and TGFbeta Dominant Negative Receptor (DNR) Expressing EBV Specific Lymphocytes for Subjects With Advanced Her2 Positive Malignancy (HERCREEM)
- ClinicalTrials.gov ID
- NCT00889954
- Acronym / sponsor ID
- HERCREEM / 24486-HERCREEM
- Conditions
- HER2 Positive Malignancies
- Keywords
- EBV+, Her2, TGFBeta, EBV positive, HER 2 positive malignancy, cytotoxic T lymphocytes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 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
- May 2009
- Primary completion
- Jul 2015 (actual)
- Study completion
- 21 Jan 2018 (actual)
- First posted
- 29 Apr 2009 (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.
Patients have advanced stage cancer. This study is a gene transfer research study using special immune cells.
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. Investigators hope that both will work better together. Antibodies are proteins that protect the body from diseases caused from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients.
T lymphocytes can kill tumor cells but there are normally not enough of them or they are not able to kill all the tumor cells. We have done research in which we have grown "extra" T lymphocytes. We have added genes to those T lymphocytes to help them to recognize tumor cells. Although the results have been promising, we are still doing more research in this area.
Antibodies usually circulate in blood and are secreted by other cells of the immune system in response to the presence of germs or abnormal cells in the body. The antibody used in this study is called anti-HER2 (Human Epidermal Growth Factor Receptor 2). This antibody sticks to HER2-positive cancer cells because of a substance on the outside of these cells called HER2.
Detailed description
The patient will give blood to grow T cells on either one to two separate occasions. Then, the EBV-specific T cells will be made. These cells will be grown and frozen. To get the HER2 antibody (and the CD28) and the DNR to attach to the surface of the EBV-T cells, the antibody gene and the DNR gene will be inserted into the EBV-T cell. This is done with two viruses called retroviruses that have been made for this study. One will carry the antibody gene into the T cell and the other the DNR gene.
When the patient is enrolled on the study, they will be assigned to a dose of HER2-DNR EBV-T cells. The subject will be given one dose of cells into the vein through an IV line. 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. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TGFBeta resistant HER2/EBV-CTLs | Experimental | Biological: TGFBeta resistant HER2/EBV-CTLsThe following dose levels will be evaluated: Dose Level 1: 1 x 10^4 cells/m^2 Dose Level 2: 3 x 10^4 cells/m^2 Dose Level 5: 1 x 10^6 cells/m^2 Dose Level 6: 3 x 10^6 cells/m^2 Dose Level 7: 1 x 10^7 cells/m^2 Dose Level 8: 3 x 10^7 cells/m^2 Dose Level 9:1 x 10^8 cells/m^2 |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- The patient must meet the following eligibility inclusion criteria at the time of PROCUREMENT:
- Diagnosis of advanced stage* or metastatic HER2-positive cancer (Immunohistochemistry or reverse transcription-polymerase chain reaction (RT-PCR) is used to determine HER2 positivity)
- Breast ≥Stage IIIb Colon cancer ≥Stage IIIb Esophageal cancer ≥Stage IIIb Gastric carcinoma ≥Stage IIIb Head and Neck cancer Stage IV Lung cancer ≥Stage IIIb Pancreatic cancer Stage IV Prostate cancer Stage IV
- it is expected that the majority of patients who will be accrued on the protocol will have one of the HER2-positive malignancies listed in the table. If the patient's malignancy is not listed we will use ≥ Stage IIIb as the definition of advanced stage disease. If Stage IIIb is not part of the staging system for the individual tumor, Stage IV will be used.
- For World Health Organization grade III and IV brain tumors):patients will be eligible, who have recurrent or progressive disease after front line therapy.
Key exclusion criteria (7 listed)
- 1. Known HIV positivity
- 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 |
|---|---|---|
| TGFBeta resistant HER2/EBV-CTLsAlso: HER2-DNR EBV T cellsEach patient will receive one injection of the TGFBeta resistant HER2/EBV-specific CTLs. Each pt will be followed for 6 weeks after the CTL infusion for evaluation of dose limiting toxicity (DLT). Patients may receive up to six additional doses of the T cells at 6 to 12 weeks intervals. | Biological | TGFBeta resistant HER2/EBV-CTLs |
Primary outcome
Number of Patients with dose limiting toxicity.
Time frame: 6 weeks
Determine safety of one IV injection of autologous TGFBeta-resistant cytotoxic T cells (CTL) directed to Epstein Barr virus (EBV) through their native receptor and HER2 through their chimeric antigen receptor (CAR) in patients with advanced HER2- positive cancers.
2 secondary outcomes
Area under the growth curves (AUC) over time for T cell frequencies.
Time frame: 15 years
Decrease in tumor after the CTL infusion
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 18 Sep 2018.
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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.
Stepehen Gottschalk, 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 TGFBeta resistant HER2/EBV-CTLs in people with HER2 Positive Malignancies, 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 24 inclusion and 7 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 18 Sep 2018. 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 Patients with dose limiting toxicity. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Sep 2018.