T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies
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|ClinicalTrials.gov Identifier: NCT02457650|
Recruitment Status : Recruiting
First Posted : May 29, 2015
Last Update Posted : August 3, 2016
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.
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.
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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Carcinoma Breast Cancer Esophagus Carcinoma Lung Cancer Melanoma Multiple Myeloma Neuroblastoma Ovarian Cancer Synovial Sarcoma Other Metastatic Solid Cancers||Drug: Cyclophosphamide Drug: Fludarabine Biological: Anti-NY ESO-1 TCR-transduced T cells||Phase 1|
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.
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.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Malignancies That Express NY-ESO-1 With T Cell Receptor-transduced T Cells Targeting NY-ESO-1|
|Study Start Date :||April 2015|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2019|
Experimental: Anti-NY ESO-1 TCR-transduced T cells
Patients will receive a lymphodepleting conditioning regimen followed by an infusion of anti-NY-ESO-1 TCR-transduced T cells.
On days -7 through -6, Cyclophosphamide 60mg/kg/day IV will be infused over 60 minutes.
On days -5 through -1, Fludarabine 25mg/m2/day IV will be infused over 30 minutes.
Biological: Anti-NY ESO-1 TCR-transduced T cells
Modified cells will be infused IV over 30 minutes.
- 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.
- Number of participants with Clinical responses [ Time Frame: 2 years ]To determine if the treatment can result in clinical regression of malignant tumors in the patients.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02457650
|Contact: Mingjun Wang, M.D., Ph.D.||firstname.lastname@example.org|
|Contact: Geng Tian, M.D., Ph.Demail@example.com|
|Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University||Recruiting|
|Shenzhen, Guangdong, China, 518035|
|Contact: Mingjun Wang, M.D., Ph.D. 15814723218 firstname.lastname@example.org|
|Contact: Geng Tian, M.D., Ph.D. 13724395569 email@example.com|
|Principal Investigator: Geng Tian, M.D., Ph.D.|
|Principal Investigator: Mingjun Wang, M.D., Ph.D.|