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Trial registered on ANZCTR
Registration number
ACTRN12609000173291
Ethics application status
Approved
Date submitted
26/03/2009
Date registered
15/04/2009
Date last updated
6/07/2012
Type of registration
Retrospectively registered
Titles & IDs
Public title
A Phase II Study of the Impact of Two Different Schedules of Thymoglobulin on the Incidence of Extensive Chronic Graft Verus Host Disease (GVHD) in Patients Undergoing Unrelated Donor or Mismatched Related Donor Stem Cell Transplantation
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Scientific title
A Phase II Study of the Impact of Two Different Schedules of Thymoglobulin on the Incidence of Extensive Chronic Graft Versus Host Disease (GVHD) in Undergoing Unrelated Donor or Mismatched Related Donor Stem Cell Transplantation for Haematological Malignancy
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Chronic Graft versus Host Disease in Haematology Malignancy Patients receiving donor stem cell transplantation
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Condition category
Condition code
Cancer
4817
4817
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0
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Other cancer types
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Thymoglobulin - 2 different schedules:
Canadian patients will receive:
0.5mg/kg day -2
2mg/kg day -1
2mg/kg day 0 before graft infusion
Australian patients will receive the same dose and schedule of Thymoglobulin except the doses will be given on day -3, day -2 and day -1 respectively.
Thymoglobulin will be given as a continuous IV infusion over 4-8 hrs
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Intervention code [1]
4288
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Treatment: Drugs
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Comparator / control treatment
The comparison group will consist of historical `controls' who had a peripheral blood stem cell (PBSC) unrelated donor transplant at Royal Melbourne Hospital (RMH) from 2000-2006. Historical controls of patients did not receive Thymoglobulin (or any form of T cell depletion), but are otherwise comparable for other transplant characteristics. At RMH we have an extensive data set on these patients including all information proposed to be collected in the prospective study group
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Control group
Historical
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Outcomes
Primary outcome [1]
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To compare the incidence of extensive chronic GVHD at one and two years in patients receiving Thymoglobulin prophylaxis, with historical controls of patients who did not receive Thymoglobulin (or any form of T cell depletion), but who are otherwise comparable for other transplant characteristics. For this purpose patients receiving the two different Thymoglobulin schedules will be analysed together. Grading of acute GVHD will be done according to Glucksberg/Seattle criteria. The scoring system from Filipovich (BBMT 2005) will be used to grade the severity of chronic GVHD.
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Assessment method [1]
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Timepoint [1]
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1 and 2 years after study opening
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Primary outcome [2]
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To evaluate the relationship between rabbit IgG levels at the time of stem cell infusion and GVHD outcome. This will be using an assay on a blood sample.
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Assessment method [2]
5677
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Timepoint [2]
5677
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1 and 2 years after study opening
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Secondary outcome [1]
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To compare the incidence between the two groups (thymoglobulin vs no thymoglobulin) of cytomegalovirus (CMV)reactivation and disease. Patients will undergo weekly molecular monitoring for CMV reactivation at least until day 100. Patients with histological evidence of organ infection with CMV will be regarded as having CMV disease
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Assessment method [1]
241570
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Timepoint [1]
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Weekly until at least day 100
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Secondary outcome [2]
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To describe the effect of Thymoglobulin prophylaxis on various immunological parameters using blood tests. To determine the counts of the following mononuclear cell subsets:
B cells, CD4 T cells, CD8 T cells, Regulatory T cells, NKT cells, NK cells, Monocytes, Dendritic cells and HLADR high
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Assessment method [2]
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Timepoint [2]
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1 and 2 years after study opening
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Secondary outcome [3]
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To compare the incidence of extensive chronic GVHD between the two different thymoglobulin schedules. Grading of acute GVHD will be done according to Glucksberg/Seattle criteria. The scoring system from Filipovich (BBMT 2005) will be used to grade the severity of chronic GVHD.
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Assessment method [3]
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Timepoint [3]
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1 and 2 years after study opening
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Secondary outcome [4]
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To compare the incidence of acute GVHD grades II-IV and III-IV between the two groups (thymoglobulin vs no thymoglobulin). Grading of acute GVHD will be done according to Glucksberg/Seattle criteria.
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Assessment method [4]
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Timepoint [4]
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1 and 2 years after study opening
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Secondary outcome [5]
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To compare the incidence between the two groups (thymoglobulin vs no thymoglobulin) of Epstein-Barr Virus (EBV) reactivation (detectability in plasma by polymerase chain reaction (PCR)) and post-transplant lymphoproliferative disorder (PTLD). This will be measured by Computed tomography (CT) scan and or a biopsy and EBV PCR.
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Assessment method [5]
241643
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Timepoint [5]
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1 and 2 years after study opening
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Secondary outcome [6]
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To compare the incidence between the two groups (thymoglobulin vs no thymoglobulin) of other infections including clinical (microbiologically undocumented) infections and definite (microbiologically documented) infections
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Assessment method [6]
241644
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Timepoint [6]
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1 and 2 years after study opening
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Secondary outcome [7]
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To compare the incidence between the two groups (thymoglobulin vs no thymoglobulin) of relapse in patients with standard risk and advanced disease. Relapse will be diagnosed by blood tests, Bone Marrow biopsy or Computed tomography (CT) scans as appropriate.
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Assessment method [7]
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Timepoint [7]
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1 and 2 years after study opening
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Secondary outcome [8]
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To compare the incidence between the two groups (thymoglobulin vs no thymoglobulin) of treatment-related mortality (TRM) and overall and disease-free survival. Disease-free survival is defined as survival without recurrence of the underlying disease.
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Assessment method [8]
241646
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Timepoint [8]
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1 and 2 years after study opening
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Secondary outcome [9]
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To compare the incidence of moderate/severe chronic GVHD between the two different thymoglobulin schedules. Moderate chronic GVHD involves (1) at least one organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) or (2) three or more organs or sites with no clinically significant functional impairment (maximum score of 1 in all affected organs or sites). A lung score of 1 will also be considered moderate chronic GVHD. Severe chronic GVHD indicates major disability caused by chronic GVHD (score of 3 in any organ or site). A lung score of 2 or greater will also be considered severe chronic GVHD
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Assessment method [9]
241648
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Timepoint [9]
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1 and 2 years after study opening
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Eligibility
Key inclusion criteria
1.age > 18 years
2.undergoing an unrelated or mismatched related peripheral blood stem cell (PBSC) allograft
3.no contra-indication to receiving Thymoglobulin
4.life expectancy >3 months
5.absence of active invasive fungal infection at the time of transplant
6.myeloablative conditioning (including cy/TBI, VP16/TBI fludarabine-melphalan >120mg/m2, fludarabine-busulphan at a dose at least equivalent to 3.2mg/kg intravenous (IV) per day for 4 days and by-cy. IV busulphan will be used, given as a single daily dose of 3.2mg/kg at a rate of 80mg/hr. Monitoring, if available, will be done to conform with local guidelines
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Minimum age
18
Years
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Maximum age
80
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1.active invasive fungal infection at the time of transplant
2.contra-indication to receiving Thymoglobulin
3.Pregnancy
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
In Australia all patients will be on one scedule. In Canada patients will be on a different schedule
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Phase
Phase 2
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Type of endpoint/s
Efficacy
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Date of first participant enrolment
Anticipated
1/04/2009
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Actual
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
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Sample size
Target
120
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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Canada
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State/province [1]
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Calgary
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Funding & Sponsors
Funding source category [1]
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Commercial sector/Industry
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Name [1]
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Genzyme
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Address [1]
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PO Box 282 North Ryde B/C NSW 1670 AUSTRALIA
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Country [1]
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Australia
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Primary sponsor type
Hospital
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Name
The Royal Melbourne Hospital
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Address
Grattan St,
Parkville, 3050 VIC
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Country
Australia
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Secondary sponsor category [1]
4264
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None
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Name [1]
4264
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Address [1]
4264
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Country [1]
4264
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Other collaborator category [1]
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Hospital
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Name [1]
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Calgary
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Address [1]
623
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1331 - 29 Street NW
Calgary, Alberta T2N 4N2
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Country [1]
623
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Canada
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
6753
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Ethics committee address [1]
6753
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Ethics committee country [1]
6753
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Date submitted for ethics approval [1]
6753
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28/09/2008
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Approval date [1]
6753
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Ethics approval number [1]
6753
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2008.172
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Summary
Brief summary
This study is for patients with a condition in which it has been recommended that an unrelated or (less commonly) a mismatched related donor stem cell transplant be performed.
One of the major side-effects of receiving a peripheral blood stem cell transplant from an unrelated or mismatched related donor is graft vs host disease (GVHD), particularly extensive chronic GVHD which can occur in up to 80% of patients. Some forms of chronic GVHD, particularly of the skin, lung and liver, can be debilitating, respond poorly to therapy and result in significant impairment of quality of life and can lead to death.
The type of donor cells which are responsible for GVHD are called T cells. The number of T cells can be substantially reduced by giving the patient a drug, for three days prior to the transplant, called thymoglobulin. This drug is derived from rabbits and is an antibody which inactivates or “depletes” many of the T cells as they are infused. Evidence from various studies suggests that T cell depletion of this type can substantially reduce the risk of GVHD after a transplant, with major improvements in the quality of life in surviving patients.
There are, however, potential disadvantages from T cell depletion. The same T cells which cause GVHD may also be important for engraftment (the ability of the donor stem cells to grow successfully in the recipients bone marrow and restore blood counts), immunity against viral infections (particularly in the first 3-4 months post-transplant) and a graft vs leukaemia/lymphoma effect which is when the immune system of the donor attacks any residual tumour which has survived the chemotherapy and radiotherapy.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Sarah Bascomb
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Address
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St Andrews Place
East Melbourne, VIC 3002
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Country
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Australia
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Phone
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+61 3 9656 3720
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Fax
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+61 3 9639 3745
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Email
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[email protected]
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Contact person for scientific queries
Name
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Andrew Grigg
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Address
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The Royal Melbourne Hospital
Grattan St
Parkville, VIC 3050
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Country
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Australia
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Phone
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+61 3 9342 7690
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Fax
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Email
3612
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[email protected]
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No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Documents added manually
No documents have been uploaded by study researchers.
Documents added automatically
No additional documents have been identified.
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