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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-FXY-040 | Other Grant/Funding Number | Institutional Review Board of Sun Yat-Sen University | |
| B2016-039 | Other Grant/Funding Number | ethics committee of Sun Yat-Sen University |
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| Name | Class |
|---|---|
| Sun Yat-sen University | OTHER |
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The primary objective of this study is to evaluate the safety of TSA-CTL in the treatment of advanced solid tumors.
The secondary objective of this study is to evaluate preliminarily the effect of TSA-CTL in the treatment of advanced solid tumors.
This is a single arm, open label and non-randomized clinical study with two parts.
In Part 1, 9 subjects with advanced solid tumors will be enrolled into Groups A (no non-myeloablative lymphodepletion), B and C (non-myeloablative lymphodepletion with different chemotherapy intensities) to assess the safety and dose intensity of non-myeloablative lymphodepletion chemotherapy before cell infusion.
Depending on results in Part 1, the study may proceed to Part 2, where 15 subjects with advanced solid tumors will be enrolled to receive TSA-CTL cell infusions with or without non-myeloablative lymphodepletion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| medium-dose lymphodepletion regimen | Experimental | Patients will receive medium-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. |
|
| low-dose lymphodepletion regimen | Experimental | Patients will receive low-dose lymphodepletion regimen consisting of cyclophosphamide and fludarabine followed by TSA-CTL. |
|
| No lymphodepletion regimen | Experimental | Patients will only receive TSA-CTL. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TSA-CTL | Biological | Patients will receive TSA-CTL iv over 20-30 minutes on day 0. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events as assessed by CTCAE v5.0. | Keep records the adverse events experienced by subjects in 30 days after the first infusion. | one month |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Control Rate(DCR) | DCR is defined as the proportion of participants with tumor size reduction(CR,PR) and stable disease(SD) assessed by RECIST 1.1 and iRECIST. | one year |
| overall survival(OS) |
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Inclusion Criteria:
Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiao Sh Zhang, Doctor | Sun Yat-sen University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sun Yat-Sen University Cancer Center | Guangzhou | Guangdong | 510030 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24812403 | Result | Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102. | |
| 25837513 | Result |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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|
| Cyclophosphamide | Drug | Cyclophosphamide 500 mg/m2/day iv on day -5 for one day. |
|
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| Fludarabine | Drug | Fludarabine 25 mg/m2/day iv over 30 minutes on day -5 and -4 for two days. |
|
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| Cyclophosphamide | Drug | Cyclophosphamide 500 mg/m2/day iv on day -5 and -4 for two days. |
|
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The time from the first infusion of Investigational Product until death.
| one year |
| progression-free survival(PFS) | PFS is defined as the time from the first infusion of Investigational Product until objective tumor progression, as assessed by RECIST 1.1 and iRECIST, or death, whichever occurs first. | one year |
| Duration of Response(DOR) | DOR refers to the period from the first evaluation of tumor as CR or PR to the first evaluation as PD(Progressive Disease) per RECIST1.1 and iRECIST. | one year |
| Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 2. |
| 27312342 | Result | Prickett TD, Crystal JS, Cohen CJ, Pasetto A, Parkhurst MR, Gartner JJ, Yao X, Wang R, Gros A, Li YF, El-Gamil M, Trebska-McGowan K, Rosenberg SA, Robbins PF. Durable Complete Response from Metastatic Melanoma after Transfer of Autologous T Cells Recognizing 10 Mutated Tumor Antigens. Cancer Immunol Res. 2016 Aug;4(8):669-78. doi: 10.1158/2326-6066.CIR-15-0215. Epub 2016 Jun 16. |
| 37301885 | Derived | Li D, Chen C, Li J, Yue J, Ding Y, Wang H, Liang Z, Zhang L, Qiu S, Liu G, Gao Y, Huang Y, Li D, Zhang R, Liu W, Wen X, Li B, Zhang X, Zhang X, Xu RH. A pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell therapy in patients with advanced solid tumors. Nat Commun. 2023 Jun 10;14(1):3447. doi: 10.1038/s41467-023-39225-7. |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |