Complementary vaccination protocol with dendritic cells pulsed with autologous tumour lysate in patients with resected stage III or IV melanoma: Protocol for a phase II randomised trial (ACDC Adjuvant Trial)

Laura Ridolfi, Francesco De Rosa, Laura Fiammenghi, Massimiliano Petrini, Anna Maria Granato, Valentina Ancarani, Elena Pancisi, Valentina Soldati, Serena Cassan, Jenny Bulgarelli, Angela Riccobon, Giorgia Gentili, Oriana Nanni, Massimo Framarini, Francesca Tauceri, Massimo Guidoboni

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Introduction Surgery is one of the treatments of choice for patients with a single metastasis from melanoma but is rarely curative. Such patients could potentially benefit from consolidation immunotherapy. Vaccination with dendritic cells (DCs) loaded with tumour antigens elicits a tumour-specific immune response. In our experience, patients who developed delayed type hypersensitivity (DTH) after DC vaccination showed a median overall survival (OS) of 22.9 monthsvs4.8 months for DTH-negative cases. A phase II randomised trial showed an advantage OS of a DC vaccine over a tumour cell-based vaccine (2-year OS 72% vs31%, respectively). Given that there is no standard therapy after surgical resection of single metastases, we planned a study to compare vaccination with DCs pulsed with autologous tumour lysate versus follow-up. Methods and analysis This is a randomised phase II trial in patients with resected stage III/IV melanoma. Assuming a median relapse-free survival (RFS) of 7.0 months for the standard group and 11.7 months for the experimental arm (HR 0.60), with a two-sided tailed alpha of 0.10, 60 patients per arm must be recruited. An interim futility analysis will be performed at 18 months. The DC vaccine, produced in accordance with Good Manufacturing Practice guidelines, consists of autologous DCs loaded with autologous tumour lysate and injected intradermally near lymph nodes. Vaccine doses will be administered every 4 weeks for six vaccinations and will be followed by 3 million unit /day of interleukin-2 for 5 days. Tumour restaging, blood sampling for immunological biomarkers and DTH testing will be performed every 12 weeks. Ethics and dissemination The protocol, informed consent and accompanying material given to patients were submitted by the investigator to the Ethics Committee for review. The local Ethics Committee and the Italian Medicines Agency approved the protocol (EudraCT code no.2014-005123-27). Results will be published in a peer-reviewed international scientific journal. Trial registration number 2014-005123-27.

Original languageEnglish
Article numbere021701
JournalBMJ Open
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

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Dendritic Cells
Melanoma
Vaccination
Delayed Hypersensitivity
Vaccines
Neoplasms
Ethics Committees
Survival
Medical Futility
Neoplasm Metastasis
Interleukin-5
Neoplasm Antigens
Informed Consent
Practice Guidelines
Ethics
Immunotherapy
Interleukin-2
Biomarkers
Lymph Nodes
Research Personnel

Keywords

  • adjuvant immunotherapy
  • dendritic cell
  • melanoma
  • vaccine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Complementary vaccination protocol with dendritic cells pulsed with autologous tumour lysate in patients with resected stage III or IV melanoma : Protocol for a phase II randomised trial (ACDC Adjuvant Trial). / Ridolfi, Laura; De Rosa, Francesco; Fiammenghi, Laura; Petrini, Massimiliano; Granato, Anna Maria; Ancarani, Valentina; Pancisi, Elena; Soldati, Valentina; Cassan, Serena; Bulgarelli, Jenny; Riccobon, Angela; Gentili, Giorgia; Nanni, Oriana; Framarini, Massimo; Tauceri, Francesca; Guidoboni, Massimo.

In: BMJ Open, Vol. 8, No. 8, e021701, 01.08.2018.

Research output: Contribution to journalArticle

Ridolfi, Laura ; De Rosa, Francesco ; Fiammenghi, Laura ; Petrini, Massimiliano ; Granato, Anna Maria ; Ancarani, Valentina ; Pancisi, Elena ; Soldati, Valentina ; Cassan, Serena ; Bulgarelli, Jenny ; Riccobon, Angela ; Gentili, Giorgia ; Nanni, Oriana ; Framarini, Massimo ; Tauceri, Francesca ; Guidoboni, Massimo. / Complementary vaccination protocol with dendritic cells pulsed with autologous tumour lysate in patients with resected stage III or IV melanoma : Protocol for a phase II randomised trial (ACDC Adjuvant Trial). In: BMJ Open. 2018 ; Vol. 8, No. 8.
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abstract = "Introduction Surgery is one of the treatments of choice for patients with a single metastasis from melanoma but is rarely curative. Such patients could potentially benefit from consolidation immunotherapy. Vaccination with dendritic cells (DCs) loaded with tumour antigens elicits a tumour-specific immune response. In our experience, patients who developed delayed type hypersensitivity (DTH) after DC vaccination showed a median overall survival (OS) of 22.9 monthsvs4.8 months for DTH-negative cases. A phase II randomised trial showed an advantage OS of a DC vaccine over a tumour cell-based vaccine (2-year OS 72{\%} vs31{\%}, respectively). Given that there is no standard therapy after surgical resection of single metastases, we planned a study to compare vaccination with DCs pulsed with autologous tumour lysate versus follow-up. Methods and analysis This is a randomised phase II trial in patients with resected stage III/IV melanoma. Assuming a median relapse-free survival (RFS) of 7.0 months for the standard group and 11.7 months for the experimental arm (HR 0.60), with a two-sided tailed alpha of 0.10, 60 patients per arm must be recruited. An interim futility analysis will be performed at 18 months. The DC vaccine, produced in accordance with Good Manufacturing Practice guidelines, consists of autologous DCs loaded with autologous tumour lysate and injected intradermally near lymph nodes. Vaccine doses will be administered every 4 weeks for six vaccinations and will be followed by 3 million unit /day of interleukin-2 for 5 days. Tumour restaging, blood sampling for immunological biomarkers and DTH testing will be performed every 12 weeks. Ethics and dissemination The protocol, informed consent and accompanying material given to patients were submitted by the investigator to the Ethics Committee for review. The local Ethics Committee and the Italian Medicines Agency approved the protocol (EudraCT code no.2014-005123-27). Results will be published in a peer-reviewed international scientific journal. Trial registration number 2014-005123-27.",
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AU - De Rosa, Francesco

AU - Fiammenghi, Laura

AU - Petrini, Massimiliano

AU - Granato, Anna Maria

AU - Ancarani, Valentina

AU - Pancisi, Elena

AU - Soldati, Valentina

AU - Cassan, Serena

AU - Bulgarelli, Jenny

AU - Riccobon, Angela

AU - Gentili, Giorgia

AU - Nanni, Oriana

AU - Framarini, Massimo

AU - Tauceri, Francesca

AU - Guidoboni, Massimo

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N2 - Introduction Surgery is one of the treatments of choice for patients with a single metastasis from melanoma but is rarely curative. Such patients could potentially benefit from consolidation immunotherapy. Vaccination with dendritic cells (DCs) loaded with tumour antigens elicits a tumour-specific immune response. In our experience, patients who developed delayed type hypersensitivity (DTH) after DC vaccination showed a median overall survival (OS) of 22.9 monthsvs4.8 months for DTH-negative cases. A phase II randomised trial showed an advantage OS of a DC vaccine over a tumour cell-based vaccine (2-year OS 72% vs31%, respectively). Given that there is no standard therapy after surgical resection of single metastases, we planned a study to compare vaccination with DCs pulsed with autologous tumour lysate versus follow-up. Methods and analysis This is a randomised phase II trial in patients with resected stage III/IV melanoma. Assuming a median relapse-free survival (RFS) of 7.0 months for the standard group and 11.7 months for the experimental arm (HR 0.60), with a two-sided tailed alpha of 0.10, 60 patients per arm must be recruited. An interim futility analysis will be performed at 18 months. The DC vaccine, produced in accordance with Good Manufacturing Practice guidelines, consists of autologous DCs loaded with autologous tumour lysate and injected intradermally near lymph nodes. Vaccine doses will be administered every 4 weeks for six vaccinations and will be followed by 3 million unit /day of interleukin-2 for 5 days. Tumour restaging, blood sampling for immunological biomarkers and DTH testing will be performed every 12 weeks. Ethics and dissemination The protocol, informed consent and accompanying material given to patients were submitted by the investigator to the Ethics Committee for review. The local Ethics Committee and the Italian Medicines Agency approved the protocol (EudraCT code no.2014-005123-27). Results will be published in a peer-reviewed international scientific journal. Trial registration number 2014-005123-27.

AB - Introduction Surgery is one of the treatments of choice for patients with a single metastasis from melanoma but is rarely curative. Such patients could potentially benefit from consolidation immunotherapy. Vaccination with dendritic cells (DCs) loaded with tumour antigens elicits a tumour-specific immune response. In our experience, patients who developed delayed type hypersensitivity (DTH) after DC vaccination showed a median overall survival (OS) of 22.9 monthsvs4.8 months for DTH-negative cases. A phase II randomised trial showed an advantage OS of a DC vaccine over a tumour cell-based vaccine (2-year OS 72% vs31%, respectively). Given that there is no standard therapy after surgical resection of single metastases, we planned a study to compare vaccination with DCs pulsed with autologous tumour lysate versus follow-up. Methods and analysis This is a randomised phase II trial in patients with resected stage III/IV melanoma. Assuming a median relapse-free survival (RFS) of 7.0 months for the standard group and 11.7 months for the experimental arm (HR 0.60), with a two-sided tailed alpha of 0.10, 60 patients per arm must be recruited. An interim futility analysis will be performed at 18 months. The DC vaccine, produced in accordance with Good Manufacturing Practice guidelines, consists of autologous DCs loaded with autologous tumour lysate and injected intradermally near lymph nodes. Vaccine doses will be administered every 4 weeks for six vaccinations and will be followed by 3 million unit /day of interleukin-2 for 5 days. Tumour restaging, blood sampling for immunological biomarkers and DTH testing will be performed every 12 weeks. Ethics and dissemination The protocol, informed consent and accompanying material given to patients were submitted by the investigator to the Ethics Committee for review. The local Ethics Committee and the Italian Medicines Agency approved the protocol (EudraCT code no.2014-005123-27). Results will be published in a peer-reviewed international scientific journal. Trial registration number 2014-005123-27.

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