NY-ESO-1-specific T Cell Receptor (TCR) T Cell in Sarcoma
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|ClinicalTrials.gov Identifier: NCT03462316|
Recruitment Status : Recruiting
First Posted : March 12, 2018
Last Update Posted : January 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Bone Sarcoma Soft Tissue Sarcoma||Biological: NY-ESO-1（TCR Affinity Enhancing Specific T cell Therapy）||Phase 1|
This is a one arm, open label, dose escalation, single dose phase I study. The investigators include first-line treatment failed advanced patients with bone or soft tissue sarcoma and without standard regimen;TCR-T cell therapy has made a breakthrough for tumors in recent years. Phase I/II trial of NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma, conducted by the Rosenberg team at the National Cancer Institute, showed that 61% Synovial cell sarcoma patients and 55% melanoma patients benefit from this treatment, without severe side effects found in T cell receptor (TCR) transduced T-Cell Immunotherapy.
This clinical trial is mainly focused on cancer-testis antigen, because it is not expressed in normal cells. NY-ESO-1 antigen as one member of cancer-testis antigen, is commonly expressed in 10-50% of melanoma, lung, liver, esophageal, breast, prostate, bladder, thyroid and ovarian cancer cases, 60% of multiple myeloma cases, and 70-80% of synovial sarcoma. NY-ESO-1 expression was also found in 88.2% of myxoid liposarcomas, 61.1% of synovial sarcomas, 31.3% of osteosarcomas, 21.4% of pleomorphic liposarcomas, 16.7% of desmoplastic small round cell tumors, and 14.3% of chondrosarcomas. The NY-ESO-1 TCR cell therapy for synovial sarcoma and melanoma has benefited many patients, but its effect on bone and soft tissue sarcoma is still unknown. So the investigators plan to explore its efficacy.
The patients must meet the two criteria: HLA-A*0201+ and NY-ESO-1 positive cells≥25% by immunohistochemistry. By this trial, the dose-limiting toxicity (DLT) and maximum tolerance (MTD) will be initially identified.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||To Evaluate the Efficacy of NY-ESO-1-specific T Cell Receptor (TCR) Affinity Enhancing Specific T Cell in Bone and Soft Tissue Sarcoma|
|Actual Study Start Date :||May 21, 2018|
|Estimated Primary Completion Date :||June 15, 2019|
|Estimated Study Completion Date :||February 15, 2020|
Experimental: NY-ESO-1 TCR Specific T cell Therapy
NY-ESO-1 TCR specific T cells are prepared by lentiviral infection. Seven days before TCR-T cell reinfusion, the subjects received low-dose cyclophosphamide (15mg/kg/d x 3 days) and low-dose fludarabine (15mg/m2/d x 3 days) lymphocyte clearance. Four days later, TCR-T cells were transfused back (1 x 109-5 x 1010 was administered once or in stages). Then interleukin (IL)-2 subcutaneous injections (250,000 IU/twice/day) will be subcutaneously administered for 14 days concomitantly to each subject within 15-30 minutes after cell reinfusion. If the first three patients had no severe bone marrow suppression side effects (CTCAE was above grade 3) on low-dose lymphocyte clearance therapy, the dosage of cyclophosphamide (20 mg/kg/d x 3 days) and fludarabine (25 mg/m2/d x 3 days) could be increased for follow-up patients.
Biological: NY-ESO-1（TCR Affinity Enhancing Specific T cell Therapy）
NY-ESO-1（TCR Affinity Enhancing Specific T cell Therapy）
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v3.0 [ Time Frame: 270 days ]safety evaluation(dose-limiting toxicity and the maximum tolerance)
- clinical response rate [ Time Frame: 270 Days ]Overall Response Rate as assessed by RECIST criteria
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): NCT03462316
|Sun Yat-Sen Univerisity||Recruiting|
|Guangzhou, Guangdong, China, 510000|
|Contact: Xing Zhang, PhD,MD 86-020-87343192 firstname.lastname@example.org|
|Principal Investigator: Xing Zhang|