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The aim of this study is to investigate the toxicity and clinical response of therapy with tumor infiltrating lymphocytes as treatment for advanced melanoma.
Patient will receive a single treatment consisting of conditioning chemotherapy for seven days (cyclophosphamide for two days and fludarabine for five days), intravenous infusion of high number of in vitro expanded tumor infiltrating lymphocytes followed by two weeks with daily low-dose interleukine-2. Patients will be evaluated for toxicity, tumor response, and immune response.
After the first 6 patients the treatment with IL-2 has been changed to include higher doses of IL-2 (see intervention)
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cyclophosphamide, fludarabine, T-cells, Interleukin-2 | Biological | Two days of cyclophosphamide (60 mg/kg i.v.) and five days of fludarabine (25 mg/m2 i.v.). Infusion of Tumor Infiltrating Lymphocytes (10e9-10e10 cells). Followed by daily sc injections of 2 MIE Interleukin-2 for two weeks. After the first 6 patients the dose of IL-2 has been changed to an i.v. decrescendo regimen using 18 MIU/m2 infused over 6, 12 and 24 hours and then 4.5 MIU/m2 infused over 24 hours for three days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| toxicity | week 0 to 20 |
| Measure | Description | Time Frame |
|---|---|---|
| immune response | week 0 to 20 | |
| tumor response | week 8 and every 3rd week until progression |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Inge Marie Svane, Professor, MD | Department of Oncology, Copenhagen University Hospital, Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark | Study Director |
| Rikke Andersen, MD | Center for Cancer Immune Therapy, department of Oncology, Herlev Hospital, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Oncology, Copenhagen University Hospital, Herlev | Herlev | 2730 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37490916 | Derived | Dolton G, Rius C, Wall A, Szomolay B, Bianchi V, Galloway SAE, Hasan MS, Morin T, Caillaud ME, Thomas HL, Theaker S, Tan LR, Fuller A, Topley K, Legut M, Attaf M, Hopkins JR, Behiry E, Zabkiewicz J, Alvares C, Lloyd A, Rogers A, Henley P, Fegan C, Ottmann O, Man S, Crowther MD, Donia M, Svane IM, Cole DK, Brown PE, Rizkallah P, Sewell AK. Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy. Cell. 2023 Aug 3;186(16):3333-3349.e27. doi: 10.1016/j.cell.2023.06.020. Epub 2023 Jul 24. | |
| 34813506 |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| 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 |
| D007376 | Interleukin-2 |
| C042382 | fludarabine phosphate |
| C082598 | aldesleukin |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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| Derived |
| Kristensen NP, Heeke C, Tvingsholm SA, Borch A, Draghi A, Crowther MD, Carri I, Munk KK, Holm JS, Bjerregaard AM, Bentzen AK, Marquard AM, Szallasi Z, McGranahan N, Andersen R, Nielsen M, Jonsson GB, Donia M, Svane IM, Hadrup SR. Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive cell therapy with tumor-infiltrating lymphocytes in melanoma. J Clin Invest. 2022 Jan 18;132(2):e150535. doi: 10.1172/JCI150535. |
| 32747469 | Derived | Borch TH, Andersen R, Ellebaek E, Met O, Donia M, Svane IM. Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma. J Immunother Cancer. 2020 Jul;8(2):e000668. doi: 10.1136/jitc-2020-000668. |
| 27006492 | Derived | Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, Holmich LR, Hendel HW, Met O, Andersen MH, Thor Straten P, Svane IM. Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. Clin Cancer Res. 2016 Aug 1;22(15):3734-45. doi: 10.1158/1078-0432.CCR-15-1879. Epub 2016 Mar 22. |
| 23014345 | Derived | Donia M, Hansen M, Sendrup SL, Iversen TZ, Ellebaek E, Andersen MH, Straten Pt, Svane IM. Methods to improve adoptive T-cell therapy for melanoma: IFN-gamma enhances anticancer responses of cell products for infusion. J Invest Dermatol. 2013 Feb;133(2):545-52. doi: 10.1038/jid.2012.336. Epub 2012 Sep 27. |
| 22909342 | Derived | Ellebaek E, Iversen TZ, Junker N, Donia M, Engell-Noerregaard L, Met O, Holmich LR, Andersen RS, Hadrup SR, Andersen MH, thor Straten P, Svane IM. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. J Transl Med. 2012 Aug 21;10:169. doi: 10.1186/1479-5876-10-169. |
| 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 |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |