ActivePhase 2ACTRN12612001101875

A phase I/II study of dendritic cell vaccination with NY-ESO-1 and alpha-galactosylceramide in patients with metastatic melanoma.

A phase I/II trial of immunisation with autologous dendritic cells loaded with NY-ESO-1 and Alpha-galactosylceramide in patients with high-risk surgically resected stage II, III or IV melanoma

Sponsor

Malaghan Institute of Medical Research

Enrollment

46 participants

Start Date

Nov 4, 2013

Study Type

Interventional

Conditions

Malignant Melanoma

Summary

Dendritic cells are cells that stimulate strong immune responses in the body. This study is looking at using dendritic cells to stimulate an immune response to a protein called NY-ESO-1 which is found in melanoma, and also to proteins found in influenza. The main purpose of the study is to see if adding an agent called alpha-galactosylceramide will improve the immune responses generated. This is a randomised study (allocation to a treatment is random), where by chance the study participant is allocated to one of two treatment groups. Neither the participant or the treating health professionals will know which treatment arm the person is on. Group 1 will receive a dendritic cell vaccine which contains fragments of NY-ESO-1 and influenza proteins. Two doses will be given 28 days apart. Group 2 will receive a dendritic cell vaccine which contains fragments from NY-ESO-1, influenza proteins and alpha-Galactosylceramide. Two doses will be given 28 days apart. Following this: Group1 will then receive 2 further vaccine treatments. This time they will receive the dendritic cell vaccine which contains the fragments of NY-ESO-1, influenza proteins and alpha-galactosylceramide. Group 2 will be randomised again. They will either complete 2 further courses of their vaccine schedule or they will be observed only. Blood samples wil be taken from participants regularly to measure the size of the immune responses generated.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria21

Patients must meet all the following criteria to be considered for inclusion in this study:
Able to give written informed consent and aged 18 years or over.
Histologically proven, fully resected American Joint Committee on Cancer (AJCC) Stage II, III, IV malignant cutaneous melanoma.
Full recovery from surgery (a minimum of 2 weeks should have elapsed since most recent surgery).
The patient must have been rendered disease free for no more than 12 months from surgery before study treatment.
ECOG performance status less than or equal to 2.
Geographically accessible to the Wellington Blood and Cancer Centre (WBCC) or prepared to travel regularly to Wellington for treatment and follow-up for the duration of the study.
Patients must have normal haematological, liver or renal parameters as indicated by:
i) Haemoglobin > 100 g/L
ii) Platelet count > 100 x109/L
iii) Neutrophil count > 1.5 x 109/L
iv) Lymphocytes > or = 0.8 x 109/L
v) Alanine Transaminase (ALT) less than or equal to 2.5 Upper Limit of Normal (ULN)
vi) Alkaline Phosphatase (ALP) less than or equal to 2.5 ULN
vii) Bilirubin less than or equal to 1.5 ULN
viii) Creatinine < 1.5 x ULN
If childbearing potential female, prepared to use contraception for the duration of the trial. Postmenopausal status is defined as meeting one or more of the following criteria:
i) over the age of 60
ii) bilateral oophorectomy
iii) aged up to and including 60 years of age with a uterus and amenorrhoea for at least 12 months
iv) aged up to and including 60 years of age without a uterus and with Follicle-stimulating hormone (FSH) >30 IU/L

Exclusion Criteria12

Patients presenting with any of the following criteria are excluded from this study:
Mucosal or ocular melanoma.
Prior chemotherapy or radiotherapy for advanced melanoma within 6 weeks of randomisation to the study.
Received any prior immune therapy.
Pregnant or breastfeeding women.
Diagnosis of any other previous cancer in the past 5 years (except non-melanoma skin cancer or in situ cancer of the cervix).
Serology indicating active infection with Hepatitis B, C or Human immunodeficiency virus (HIV.)
Uncontrolled or unstable autoimmune disease such as Systemic Lupus Erythematosus (SLE), sarcoidosis, rheumatoid arthritis, glomerulonephritis or vasculitis
Previous use of long-term immunosuppressive therapy in recent months. Must have three months off steroids before entry into the study.
Patients with co-morbid conditions that would require long term use (> 1 month) of systemic corticosteroids during study treatment (e.g. chronic obstructive pulmonary disease [COPD]). Steroid use less than or equal to 1 month is permissible.
Concurrent major organ dysfunction or unstable medical condition.
Unable to comply with study requirements as judged by the investigator.

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Interventions

The intervention arm will receive Dendritic Cell Vaccine + alpha-galactosylceramide (DCV+alpha-GalCer) - a 50:50 mixture of autologous dendritic cells loaded with NY-ESO1 peptides and alpha-galactosylceramide, and autologous dendritic cells loaded with influenza peptides and alpha-galactosylceramide. Vaccines are administered intravenously on Day One of cycles one and two. Participants are then randomised to either recieve two further vaccines or for observation. If randomised to the vaccine arm, vaccines are given on day one of cycles three and four. Vaccines have a dose of 10 x 10^6 cells (2ml volume). Each cycle is 28 days.