Bladder CarcinomaPhase 1NCT02457650
T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies
A Phase 1 study testing Cyclophosphamide, Fludarabine and Anti-NY ESO-1 TCR-transduced T cells in people with Bladder Carcinoma and Breast Cancer, run by Shenzhen Second People's Hospital at 1 site in China.
Trial summary
Background: Autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies. The patients pretreated with a lymphodepleting preconditioning regimen will be monitored after infusion of anti-NY-ESO-1 TCR-transduced T cells for… Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- Bladder Carcinoma, Breast Cancer, Esophagus Carcinoma
- What is being tested?
- Cyclophosphamide, Fludarabine and Anti-NY ESO-1 TCR-transduced T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteChina
- Study dates
- Apr 2015to Dec 2019
- 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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Must be pathology or cytology confirmed cancer patients with age of one year old and over；
- Must be HLA-A2 positive, and cancer tissues express NY-ESO-1；
- There is at least one measurable disease: diameter ≥20mm or spiral CT≥10mm；
- Willing to sign a durable power of attorney；
- Able to understand and sign the Informed Consent Document；
- Performance status：ECOG 0-2；
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- Life expectancy：More than 3 months；
- Patients must be willing to practice birth control for four months after receiving a lymphodepleting preconditioning regimen；
- Patients with no pregnancy and lactation；
- Hematopoietic： (1) Absolute neutrophil count > 1000/mm3 without support of filgrastim； (2) Platelet count > 100,000/mm3； (3) Hemoglobin > 8.0 g/dL； (4) lymphocyte count >500/mm3； (5) WBC > 3,000/mm3；
- Chemistry： (1) AST and ALT < 2.5 times upper limit of normal； (2) Serum creatinine≤1.6 mg/dl； (3) Bilirubin ≤1.5 mg/dL（3.0 mg/dL in patients with Gilbert's syndrome）；
- Seronegative for hepatitis B and C viruses；
- Seronegative for human immunodeficiency virus (HIV) antibody；
- More than four weeks must have elapsed since any prior systemic therapy at the time of randomization, and patients' toxicities must have recovered to a grade 1 or less (except for alopecia or vitiligo). Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria；
- Six weeks must have elapsed since any prior anti-CTLA4 antibody therapy to allow antibody levels to decline. Patients who have previously received any anti-CTLA4 antibody and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.
Who cannot join
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)；
- Active systemic infections；
- Coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system；
- Concurrent use of systemic steroids；
- History of severe immediate hypersensitivity reaction to any of the agents used in this study；
- There are obvious dysfunctions in heart , liver，kidney and other vital organs
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- T cell lymphoma and leukemia patients；
- HIV positive；
- History of coronary revascularization or ischemic symptoms；
- Documented Left Ventricular Ejection Fraction (LVEF) of less than or equal to 45 percent tested in patients with: Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block；
- Documented forced expiratory volume 1 (FEV1) less than or equal to 60 percent predicted tested in patients with a prolonged history of cigarette smoking (20 pk/yrs of smoking) or symptoms of respiratory dysfunction；
- Bronchial lesions (probably shifted obstructive pneumonia or intracranial hemorrhage risk)
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University
Shenzhen, Guangdong, 518035
Mingjun Wang, M.D., Ph.D., 15814723218, mingjunw429@163.com
Geng Tian, M.D., Ph.D., 13724395569, tiangeng666@aliyun.com
About this study
Official title: Phase I Study of Malignancies That Express NY-ESO-1 With T Cell Receptor-transduced T Cells Targeting NY-ESO-1
Background:
Autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies. The patients pretreated with a lymphodepleting preconditioning regimen will be monitored after infusion of anti-NY-ESO-1 TCR-transduced T cells for adverse events, persistence of anti-NY-ESO-1 TCR-transduced T cells and treatment efficacy.
Read more
Objectives:
To evaluate the safety and the efficacy of anti-NY-ESO-1 TCR-transduced T cell-based immunotherapy for patients with NY-ESO-1- expressing malignancies.
Eligibility:
Patients older than one year of age, who have relapsed or refractory malignancies that express both NY-ESO-1 and human leukocyte antigen (HLA)-A2 molecules.
Patients must have adequate organ functions.
Design:
- Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding an HLA-A2 restricted anti-NY-ESO-1 TCR gene.
- Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.
- Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
- Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.
Read the detailed description
Despite advances has been made to date in the treatment of patients with hematologic malignancies, clinical trials targeting solid cancers have achieved limited efficacy. One important reason is due to lack of ideal cancer antigens. NY-ESO-1 is expressed in various types of cancers, including neuroblastoma, hepatoma, myeloma, melanoma, esophagus, prostate, bladder, breast and ovarian cancers. While, in normal somatic tissues, NY-ESO-1 expression is restricted to the germline cells, which lack HLA molecules and cannot present peptides derived from NY-ESO-1 for recognition by T cells. Therefore, NY-ESO-1 specific T cells will only recognize and kill NY-ESO-1-expressing cancer cells, but not normal cells, thus avoiding induction of autoimmune reaction. With these unique features, NY-ESO-1 has been selected as an attractive tumor antigen candidate for cancer immunotherapy in various clinical trials.
In this trial, autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies after they receive a lymphodepleting preconditioning regimen. The patients will be monitored after infusion of anti-NY-ESO-1 TCR-transduced T cells for adverse events, persistence of anti-NY-ESO-1 TCR-transduced T cells and treatment efficacy.
Primary objectives:
To determine the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1-expressing malignancies.
Secondary objectives:
To determine if the treatment can result in clinical regression of malignant tumors in the patients.
To determine the in vivo persistency of the anti-NY-ESO-1 TCR-transduced T cells.
- Conditions
- Bladder Carcinoma, Breast Cancer, Esophagus Carcinoma, Lung Cancer, Melanoma, Multiple Myeloma
- Being tested
- Cyclophosphamide, Fludarabine, Anti-NY ESO-1 TCR-transduced T cells
- Medical subject headings
- Urinary Bladder Neoplasms, Breast Neoplasms, Esophageal Neoplasms, Lung Neoplasms, Melanoma, Multiple Myeloma, Neuroblastoma, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
On days -7 through -6, Cyclophosphamide 60mg/kg/day IV will be infused over 60 minutes.
FludarabineDrug
On days -5 through -1, Fludarabine 25mg/m2/day IV will be infused over 30 minutes.
Anti-NY ESO-1 TCR-transduced T cellsBiological
Modified cells will be infused IV over 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Anti-NY ESO-1 TCR-transduced T cells | Experimental | Patients will receive a lymphodepleting conditioning regimen followed by an infusion of anti-NY-ESO-1 TCR-transduced T cells. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Anti-NY ESO-1 TCR-transduced T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events
To evaluate the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1-expressing malignancies.
Measured: 8 weeks
Secondary outcomes (1)
Number of participants with Clinical responses
To determine if the treatment can result in clinical regression of malignant tumors in the patients.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2015 (estimated)
- Study startApr 2015
- Primary completionDec 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CarcinomaStudies of the same condition, open and under way.
- 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
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shenzhen Second People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shenzhen Institute for Innovation and Translational Medicine
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02457650
- Sponsor's protocol ID
- 201504002
- Status last verified
- Aug 2016
- First submitted
- 12 May 2015
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Malignancies That Express NY-ESO-1 With T Cell Receptor-transduced T Cells Targeting NY-ESO-1
- ClinicalTrials.gov ID
- NCT02457650
- Acronym / sponsor ID
- 201504002
- Conditions
- Bladder Carcinoma, Breast Cancer, Esophagus Carcinoma, Lung Cancer, Melanoma, Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Shenzhen Second People's HospitalUniversity, hospital or other
- Collaborators
- Shenzhen Institute for Innovation and Translational Medicine
- Study start
- Apr 2015
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 29 May 2015 (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.
Background:
Autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies. The patients pretreated with a lymphodepleting preconditioning regimen will be monitored after infusion of anti-NY-ESO-1 TCR-transduced T cells for adverse events, persistence of anti-NY-ESO-1 TCR-transduced T cells and treatment efficacy.
Objectives:
To evaluate the safety and the efficacy of anti-NY-ESO-1 TCR-transduced T cell-based immunotherapy for patients with NY-ESO-1- expressing malignancies.
Eligibility:
Patients older than one year of age, who have relapsed or refractory malignancies that express both NY-ESO-1 and human leukocyte antigen (HLA)-A2 molecules.
Patients must have adequate organ functions.
Design:
- Peripheral blood from patients will be collected for isolation of peripheral blood mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral vector encoding an HLA-A2 restricted anti-NY-ESO-1 TCR gene.
- Patients will receive a lymphodepleting preconditioning regimen to prepare their immune system to accept modified T cells.
- Patients will receive an infusion of their own modified T cells. They will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
- Patients will have frequent follow-up visits to monitor the persistence of modified T cells and efficacy of the treatment.
Detailed description
Despite advances has been made to date in the treatment of patients with hematologic malignancies, clinical trials targeting solid cancers have achieved limited efficacy. One important reason is due to lack of ideal cancer antigens. NY-ESO-1 is expressed in various types of cancers, including neuroblastoma, hepatoma, myeloma, melanoma, esophagus, prostate, bladder, breast and ovarian cancers. While, in normal somatic tissues, NY-ESO-1 expression is restricted to the germline cells, which lack HLA molecules and cannot present peptides derived from NY-ESO-1 for recognition by T cells. Therefore, NY-ESO-1 specific T cells will only recognize and kill NY-ESO-1-expressing cancer cells, but not normal cells, thus avoiding induction of autoimmune reaction. With these unique features, NY-ESO-1 has been selected as an attractive tumor antigen candidate for cancer immunotherapy in various clinical trials.
In this trial, autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies after they receive a lymphodepleting preconditioning regimen. The patients will be monitored after infusion of anti-NY-ESO-1 TCR-transduced T cells for adverse events, persistence of anti-NY-ESO-1 TCR-transduced T cells and treatment efficacy.
Primary objectives:
To determine the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1-expressing malignancies.
Secondary objectives:
To determine if the treatment can result in clinical regression of malignant tumors in the patients.
To determine the in vivo persistency of the anti-NY-ESO-1 TCR-transduced T cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-NY ESO-1 TCR-transduced T cells | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Anti-NY ESO-1 TCR-transduced T cellsPatients will receive a lymphodepleting conditioning regimen followed by an infusion of anti-NY-ESO-1 TCR-transduced T cells. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
Key exclusion criteria (12 listed)
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 |
|---|---|---|
| CyclophosphamideOn days -7 through -6, Cyclophosphamide 60mg/kg/day IV will be infused over 60 minutes. | Drug | Anti-NY ESO-1 TCR-transduced T cells |
| FludarabineOn days -5 through -1, Fludarabine 25mg/m2/day IV will be infused over 30 minutes. | Drug | Anti-NY ESO-1 TCR-transduced T cells |
| Anti-NY ESO-1 TCR-transduced T cellsModified cells will be infused IV over 30 minutes. | Biological | Anti-NY ESO-1 TCR-transduced T cells |
Primary outcome
Number of participants with Adverse Events
Time frame: 8 weeks
To evaluate the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1-expressing malignancies.
1 secondary outcome
Number of participants with Clinical responses
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cyclophosphamide, Fludarabine and Anti-NY ESO-1 TCR-transduced T cells in people with Bladder Carcinoma and Breast Cancer, run by Shenzhen Second People's Hospital at 1 site in China.
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 15 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mingjun Wang, M.D., Ph.D. (15814723218, mingjunw429@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (time frame: 8 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 3 Aug 2016.