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Trial registered on ANZCTR


Registration number
ACTRN12612001101875
Ethics application status
Approved
Date submitted
12/10/2012
Date registered
16/10/2012
Date last updated
18/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase I/II study of dendritic cell vaccination with NY-ESO-1 and alpha-galactosylceramide in patients with metastatic melanoma.
Scientific title
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
Secondary ID [1] 281378 0
Nil
Universal Trial Number (UTN)
U1111-1135-7521
Trial acronym
MELVAC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 287598 0
Condition category
Condition code
Cancer 287944 287944 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 285856 0
Treatment: Other
Comparator / control treatment
The comparator arm will receive Dendritic Cell Vaccine (DCV) - a 50:50 mixture of autologous dendritic cells loaded with NY-ESO1 peptides, and autologous dendritic cells loaded with influenza peptides. This will be given on day 1 of cycles 1 and 2. This group will go on to receive 2 further vaccinations with DCV+ alpha-GalCer on day 1 of cycles 3 and 4.
Vaccines are given intravenously with a dose of 10 x 10^6 cells (2ml volume). Each cycle is 28 days.
Control group
Active

Outcomes
Primary outcome [1] 288137 0
Counts of NY-ESO-1 peptide-specific T-cells.
Timepoint [1] 288137 0
These are measured by blood sampling at baseline, 14 days and 28 days after each vaccination. Enumeration of the antigen-specific T-cells will be measured by IFN-gamma ELISpot.
Primary outcome [2] 288138 0
Counts of influenza peptide-specific T-cells.
Timepoint [2] 288138 0
These are measured by blood sampling at baseline, 14 days and 28 days after each vaccination. Enumeration of the antigen-specific T-cells will be measured by IFN-gamma ELISpot.
Secondary outcome [1] 299487 0
Activation of Natural Killer T cells.
Timepoint [1] 299487 0
These will be measured by blood sampling at baseline, 6 hours and 24 hours after each vaccination. Blood sampling will enable measuring of cytokine release into serum.
Secondary outcome [2] 299488 0
Counts of Natural Killer T cells in the blood.
Timepoint [2] 299488 0
These will be measured by blood sampling at baseline, 24 hours, 14 days and 28 days after each vaccination. Enumeration of NKT-cells in the blood will be done using flow cytometry with NKT cell-specific antibody.
Secondary outcome [3] 299527 0
Measurement of NY-ESO-1 peptide-specific T-cell response following in vitro restimulation of blood samples taken from participants at baseline, Day 14 and Day 28 post vaccination.
Timepoint [3] 299527 0
Bloods will be taken from participants at baseline, Day 14 and Day 28 post vaccination. Measurement will be done by intracellular cytokine analysis.
Secondary outcome [4] 299558 0
Measurement of influenza peptide-specific T-cell response following in vitro restimulation of blood samples taken from participants at baseline, Day 14 and Day 28 post vaccination.
Timepoint [4] 299558 0
Bloods will be taken from participants at baseline, Day 14 and Day 28 post vaccination. Measurement will be done by intracellular cytokine analysis.
Secondary outcome [5] 299559 0
Safety/Adverse Events
Timepoint [5] 299559 0
Adverse events will be assessed and reported according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 from the date of consent until 30 days after the last dose of study treatment or scheduled visit at Cycle 4 for the control arm. Any protocol related toxicities will be followed up untill resolution to grade 1 or less.
Common side effects related to dendritic cell vaccination include flu like symptoms (fever, chills, headache), malaise, rigors and lethargy.

Eligibility
Key inclusion criteria
Patients must meet all the following criteria to be considered for inclusion in this study:
1. Able to give written informed consent and aged 18 years or over.
2. Histologically proven, fully resected American Joint Committee on Cancer (AJCC) Stage II, III, IV malignant cutaneous melanoma.
3. Full recovery from surgery (a minimum of 2 weeks should have elapsed since most recent surgery).
4. The patient must have been rendered disease free for no more than 12 months from surgery before study treatment.
5. ECOG performance status less than or equal to 2.
6. 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.
7. 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
8. 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients presenting with any of the following criteria are excluded from this study:
1. Mucosal or ocular melanoma.
2. Prior chemotherapy or radiotherapy for advanced melanoma within 6 weeks of randomisation to the study.
3. Received any prior immune therapy.
4. Pregnant or breastfeeding women.
5. Diagnosis of any other previous cancer in the past 5 years (except non-melanoma skin cancer or in situ cancer of the cervix).
6. Serology indicating active infection with Hepatitis B, C or Human immunodeficiency virus (HIV.)
7. Uncontrolled or unstable autoimmune disease such as Systemic Lupus Erythematosus (SLE), sarcoidosis, rheumatoid arthritis, glomerulonephritis or vasculitis
8. Previous use of long-term immunosuppressive therapy in recent months. Must have three months off steroids before entry into the study.
9. 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.
10. Concurrent major organ dysfunction or unstable medical condition.
11. Unable to comply with study requirements as judged by the investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Each patient who signs the consent form and enters into screening will be assigned a unique 5-digit identification number. The Registration Number will be automatically assigned online by the Clinical Trials Centre at Cancer Trials New Zealand (CTNZ).

Once randomised, the Registration Number will be used to identify the patient through-out the trial.

The CTNZ database will automatically randomise the patient by selecting the next treatment allocation from a pre-determined randomisation sequence and assign a blinded 3-digit Allocation Code; this blinded Allocation Code will be provided to the site online.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be carried out centrally by the Clinical Trials Centre at Cancer Trials New Zealand (CTNZ).

Random block sizes will be used to provide maximum concealment of allocation. The CTNZ database will automatically randomise the patient by selecting the next treatment allocation from a pre-determined randomisation sequence and assign a blinded 3-digit Allocation Code; this blinded Allocation Code will be provided to the site online.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
This study involves a two-step randomisation process:
- At the first randomisation, patients will be randomly allocated on a 1:1 ratio to DCV (Arm 1) or DCV+ alpha-GalCer (Arm 2) for two cycles of blinded treatment.
- At the second randomisation, patients in Arm 2 will be further randomised on a 1:1 ratio to receive two further cycles of open-label DCV+alpha-GalCer or control arm (observation).

The study also involves a crossover step:
- Having received two cycles of DCV, patients in Arm 1 will go on to receive two cycles of DCV+alpha-GalCer.
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4591 0
New Zealand
State/province [1] 4591 0
Wellington

Funding & Sponsors
Funding source category [1] 286125 0
Government body
Name [1] 286125 0
Health Research Council of New Zealand
Address [1] 286125 0
PO Box 5541
Wellesley Street
Auckland 1141
Country [1] 286125 0
New Zealand
Primary sponsor type
Charities/Societies/Foundations
Name
Malaghan Institute of Medical Research
Address
Malaghan Institute of Medical Research
P O Box 7090
Wellington 6242
Country
New Zealand
Secondary sponsor category [1] 284939 0
None
Name [1] 284939 0
Address [1] 284939 0
Country [1] 284939 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288182 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 288182 0
Northern B Health and Disability Ethics Committee
P O Box 5013
Wellington 6011
Ethics committee country [1] 288182 0
New Zealand
Date submitted for ethics approval [1] 288182 0
03/05/2013
Approval date [1] 288182 0
28/05/2013
Ethics approval number [1] 288182 0
13/NTB/5 and 13/NTB/6

Summary
Brief 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.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 34812 0
Dr Catherine Barrow
Address 34812 0
Wellington Blood and Cancer Centre
Wellington Hospital
Private Bag 7902
Wellington 6242
Country 34812 0
New Zealand
Phone 34812 0
+6443855999
Fax 34812 0
+6443855843
Email 34812 0
Catherine.Barrow@ccdhb.org.nz
Contact person for public queries
Name 18059 0
Ms Tess Ostapowicz
Address 18059 0
Wellington Hospital, Private Bag 7902, Wellington 6242
Country 18059 0
New Zealand
Phone 18059 0
+64 4 918 5110
Fax 18059 0
+ 64 4 385 5843
Email 18059 0
Tess.Ostapowicz@ccdhb.org.nz
Contact person for scientific queries
Name 8987 0
A/Prof Associate Professor Ian Hermans
Address 8987 0
Malaghan Institute of Medical Research
PO Box 7060
Wellington 6242
Country 8987 0
New Zealand
Phone 8987 0
+ 64 4 499 6914
Fax 8987 0
+64 4 499 6915
Email 8987 0
ihermans@malaghan.org.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary