Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette–Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study

Autor: José Mordoh, María Betina Pampena, Mariana Aris, Paula Alejandra Blanco, Mónica Lombardo, Erika María von Euw, Soledad Mac Keon, Michelle Yépez Crow, Alicia Inés Bravo, Juan Manuel O’Connor, Ana Gabriela Orlando, Franco Ramello, Estrella Mariel Levy, María Marcela Barrio
Jazyk: angličtina
Rok vydání: 2017
Předmět:
lcsh:Immunologic diseases. Allergy
0301 basic medicine
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
CUTANEOUS MELANOMA
PHASE II CLINICAL STUDY
medicine.medical_treatment
Immunology
Phases of clinical research
Alpha interferon
Medicina Clínica
Bacillus Calmette–Guerin
Gastroenterology
03 medical and health sciences
cutaneous melanoma
0302 clinical medicine
Internal medicine
purl.org/becyt/ford/3.2 [https]
medicine
rhGM-CSF
Immunology and Allergy
BACILLUS CALMETTE-GUERIN
Adverse effect
CSF-470 ALLOGENEIC CELL VACCINE
RHGM-CSF
business.industry
IFN-Α2B
IFN-α2b
Phase II clinical study
CSF-470 allogeneic cell vaccine
Immunotherapy
Clinical Trial
Vaccination
030104 developmental biology
030220 oncology & carcinogenesis
Toxicity
Cutaneous melanoma
purl.org/becyt/ford/3 [https]
Medicina Critica y de Emergencia
lcsh:RC581-607
business
Adjuvant
Zdroj: Frontiers in Immunology
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Frontiers in Immunology, Vol 8 (2017)
ISSN: 1664-3224
DOI: 10.3389/fimmu.2017.00625
Popis: The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB-III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine (n = 20) or to the IFN-α2b arm (n = 11). During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 107 irradiated CSF-470 cells plus 106 colony-forming units BCG plus 100 μg rhGM-CSF were administered intradermally, followed on days 2-4 by 100 μg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU)/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL) were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS) for CSF-470 was observed (p = 0.022). Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1-2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs) were grade 1. Pts in the IFN-α2b arm presented grades 2-3 hematological (7/11), hepatic (2/11), and cardiac (1/11) toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (p < 0.0001). Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged. Fil: Mordoh, Jose. Instituto Médico Especializado Alexander Fleming; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Pampena, María Betina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Aris, Mariana. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Blanco, Paula Alejandra. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina Fil: Lombardo, Mónica. Nobeltri; Argentina Fil: Von Euw, Erika María. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mac Keon, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Yepez Crow, Michelle. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina Fil: Bravo, Alicia Inés. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos ; Argentina Fil: O'Connor, Juan Manuel. Instituto Médico Especializado Alexander Fleming; Argentina Fil: Orlando, Ana Gabriela. Gobierno de Santa Fe. Hospital Central Olga Rizzi; Argentina. Instituto Oncológico Mater Dei; Argentina Fil: Ramello, Franco. Centro Médico San Lucas; Argentina Fil: Levy, Estrella Mariel. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Barrio, Maria Marcela. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Databáze: OpenAIRE
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