Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000212651
Ethics application status
Approved
Date submitted
20/02/2014
Date registered
27/02/2014
Date last updated
4/06/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Use of Tocilizumab (TCZ) to prevent acute graft versus host disease (GVHD)
Scientific title
A phase II study of humanized anti-IL-6 receptor antibody Tocilizumab (TCZ) to prevent development of acute graft versus host disease (GVHD) post Human Leuckocyte Antigen(HLA)-mismatched allogeneic haematopoietic progenitor cell transplantation (HPCT)
Secondary ID [1] 284131 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute graft versus host disease (GVHD) post HLA-matched allogeneic haematopoietic progenitor cell transplantation (HPCT) 291212 0
Condition category
Condition code
Cancer 291548 291548 0 0
Leukaemia - Acute leukaemia
Cancer 291549 291549 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Tocilizumab dose of 8mg/kg up to a maximum dose of 800mg to be administered as a single dose only. Tocilizumab is administered as an intravenous infusion over 60 minutes on day -1 of conditioning.
Intervention code [1] 288823 0
Prevention
Comparator / control treatment
This study is uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 291513 0
Incidence of grade II-IV (moderate-severe) acute GVHD will be assessed and graded according to the Seattle criteria.
Timepoint [1] 291513 0
Day + 100 post haematopoietic progenitor cell tranplantation (HPCT)
Secondary outcome [1] 306938 0
IL-6/IL-6R levels post-HPCT by both immunoassay and bioassay
Timepoint [1] 306938 0
2 years post HPCT
Secondary outcome [2] 307006 0
Immume cell reconstitution and function post-HPCT by flow cytometry and mRNA analysis
Timepoint [2] 307006 0
2 years post HPCT
Secondary outcome [3] 307007 0
Incidence of engraftment
Timepoint [3] 307007 0
1,2,3 and 12 months post HPCT
Secondary outcome [4] 307008 0
Incidence of liver toxicity at each medical review
Timepoint [4] 307008 0
2 years post HPCT
Secondary outcome [5] 307009 0
Transplant related mortality (TRM)
Timepoint [5] 307009 0
2 years post HPCT
Secondary outcome [6] 307055 0
Incidence of chronic GVHD graded according to Seattle criteria
Timepoint [6] 307055 0
2 years post HPCT
Secondary outcome [7] 307056 0
Progression free survival (PFS)
Timepoint [7] 307056 0
2 years post HPCT
Secondary outcome [8] 307057 0
Overall survival (OS)
Timepoint [8] 307057 0
2 years post HPCT
Secondary outcome [9] 307058 0
Infection rate at each medical review
Timepoint [9] 307058 0
post HPCT

Eligibility
Key inclusion criteria
Patients undertaking a T cell-replete HLA-mismatched allogeneic HPCT using either myeloablative or reduced intensity conditioning
Aged greater than or equal to 18 and less than 65 years
Life expectancy of greater than 3 months
Eastern Cooperative Oncology Group (ECOG) performance status less than 2 (Karnofsky greater than 50%)
Adequate organ function for allogeneic stem cell transplantation as per Institutional guidelines
1 or 2 Antigen HLA-mismatched sibling donor by typing at HLA-A, B, C and DRB1 and DQ loci. Only 1 antigen mismatch is allowed at HLA-A, B, C or DRB1, with / without a further mismatch at HLA-DQ.
1 or 2 HLA- matched volunteer unrelated donor (VUD) by typing at HLA-A, B, C, DRB1 and DQ loci. Only 1 antigen mismatch is allowed at HLA-A, B, C or DRB1, with / without a further mismatch at HLA-DQ.
Able and willing to provide written informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Inadequate organ function for allogeneic stem cell transplantation as per Institutional guidelines.
Patients receiving any other investigational agents.
Patients with a past history of solid tumours within prior 2 years (excluding completely excised cutaneous BCC and SCC).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements.
Known HIV, HCV or active HBV infection. Patients who are HepBcAb positive but HepBsAg negative (i.e. have had past HepB exposure) should receive lamivudine up to at least day 100 after HPCT.
Pregnant or breastfeeding, or patient with reproductive potential who is not willing to use adequate contraceptive precautions in the judgement of the Investigator. Adequate contraception is defined as a double-barrier method, i.e. using at least 2 methods of contraception e.g. 2 actual barrier methods or 1 actual barrier method and 1 hormonal method.
Patients with a past history of complicated diverticulitis, including fistulae, abscess formation or gastrointestinal (GI) perforation.
Donor is an identical twin (i.e. syngeneic)
History of allergic reactions attributed to compounds of similar chemical or biologic composition as TCZ, including known allergies to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
4/04/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 2117 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 7809 0
4029 - Royal Brisbane Hospital

Funding & Sponsors
Funding source category [1] 288761 0
Government body
Name [1] 288761 0
National Health & Medical Research Council
Country [1] 288761 0
Australia
Primary sponsor type
Hospital
Name
Royal Brisbane and Women's Hospital
Address
Butterfield Street
Herston
QLD 4029
Country
Australia
Secondary sponsor category [1] 287458 0
None
Name [1] 287458 0
Address [1] 287458 0
Country [1] 287458 0
Other collaborator category [1] 277837 0
Other
Name [1] 277837 0
Queensland Institute of Medical Research Berghofer
Address [1] 277837 0
300 Herston Rd,
Brisbane
QLD 4006,
Country [1] 277837 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290599 0
Royal Brisbane and Women's Human Research Ethics Committee
Ethics committee address [1] 290599 0
Level 7 Block 7
Royal Brisbane and Women's Hospital
Butterfield Street
Herston
QLD 4029
Ethics committee country [1] 290599 0
Australia
Date submitted for ethics approval [1] 290599 0
28/01/2014
Approval date [1] 290599 0
05/03/2014
Ethics approval number [1] 290599 0
HREC/14/QRBW/39

Summary
Brief summary
This study aims to determine whether adding the drug, Tocilizumab, to standard transplant immunosuppression is safe and effective at preventing acute graft versus host disease (GVHD).
You may be eligible to join this study if you are aged between 18 and 65 and are undertaking an HLA-mismatched allogeneic haematopoietic cell transplantation (HPCT).
Trial details
all participants inthis trial will receive a single dose of 8mg/kg Tocilizumab by a 60 minute intravenous infusion (administered via the vein). This will occur one day before your HPCT.
Participants will be assessed for up to 2 years to determine the incidence of GVHD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 46170 0
A/Prof Glen Kennedy
Address 46170 0
Royal Brisbane and Women's Hospital
Cancer Care Services
Level 5 Joyce Tweddell Building
Herston
QLD 4029
Country 46170 0
Australia
Phone 46170 0
+61 7 3646 8111
Fax 46170 0
+61 7 3646 7371
Email 46170 0
Glen.Kennedy@health.qld.gov.au
Contact person for public queries
Name 46171 0
Mrs Justine Leach
Address 46171 0
Clinical Trial Coordinator
Bone Marrow Transplant & Haematology
Cancer Care Services
Ground Floor, Building 34
Royal Brisbane and Women's Hospital
Herston
QLD 4029
Country 46171 0
Australia
Phone 46171 0
+61 7 3646 0266
Fax 46171 0
+61 7 3646 7371
Email 46171 0
justine.leach@health.qld.gov.au
Contact person for scientific queries
Name 46172 0
Prof Geoff Hill
Address 46172 0
Head, Division of Immunology
H Floor, Bone Marrow Transplant Laboratory
QIMR Berghofer
300 Herston Road
Brisbane
QLD 4006
Country 46172 0
Australia
Phone 46172 0
+61 7 3845 3763
Fax 46172 0
+61 7 3845 3509
Email 46172 0
Geoff.Hill@qimrberghofer.edu.au

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
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