Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000266662
Ethics application status
Approved
Date submitted
6/03/2014
Date registered
12/03/2014
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) randomized trial
Scientific title
A phase III randomized 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)-matched allogeneic haematopoietic progenitor cell transplantation (HPCT)
Secondary ID [1] 284132 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) 291213 0
Condition category
Condition code
Cancer 291553 291553 0 0
Leukaemia - Acute 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] 288824 0
Prevention
Comparator / control treatment
Placebo of normal saline solution to be administered as an intravenous infusion over 60 minutes on day -1 of conditioning.
Control group
Placebo

Outcomes
Primary outcome [1] 291515 0
Incidence of grade II-IV (moderate to severe) acute GVHD will be assessed and graded according to the Seattle criteria.
Timepoint [1] 291515 0
Day + 100 post HLA-matched allogeneic haematopoietic progenitor cell transplantation (HPCT)
Secondary outcome [1] 306940 0
IL-6/IL-6R levels by both immunoassay and bioassay
Timepoint [1] 306940 0
2 years post HLA-matched allogeneic HPCT
Secondary outcome [2] 307164 0
Immune cell reconstitution and function post-HPCT by flow cytometry and mRNA analysis
Timepoint [2] 307164 0
2 years post HLA-matched allogeneic HPCT
Secondary outcome [3] 307165 0
Incidence of engraftment
Timepoint [3] 307165 0
1,3 and 12 months post HPCT
Secondary outcome [4] 307166 0
Infection rate at each medical review
Timepoint [4] 307166 0
Post HLA-matched allogeneic HPCT
Secondary outcome [5] 307167 0
Incidence of liver toxicity at each medical review
Timepoint [5] 307167 0
2 years Post HLA-matched allogeneic HPCT
Secondary outcome [6] 307168 0
Incidence of chronic GVHD graded according to Seattle criteria
Timepoint [6] 307168 0
2 years Post HLA-matched allogeneic HPCT
Secondary outcome [7] 307169 0
Transplant related mortality (TRM)
Timepoint [7] 307169 0
2 years Post HLA-matched allogeneic HPCT
Secondary outcome [8] 307170 0
Progression free survival (PFS)
Timepoint [8] 307170 0
2 years Post HLA-matched allogeneic HPCT
Secondary outcome [9] 307171 0
Overall survival (OS)
Timepoint [9] 307171 0
2 years Post HLA-matched allogeneic HPCT

Eligibility
Key inclusion criteria
Patients undertaking a T cell-replete HLA-matched allogeneic HPCT using either myeloablative or reduced intensity conditioning
Acute leukaemia in complete morphological remission or myelodysplasia
Aged greater than or equal to 18 and less than 70 years
Life expectancy of greater than 3 months
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 50%)
Adequate organ function for allogeneic stem cell transplantation as per Institutional guidelines.
HLA-matched sibling donor by typing at HLA-A, B, C and DRB1 loci.
HLA- matched volunteer unrelated donor (VUD) by typing at HLA-A, B, C, DRB1 loci)
Able and willing to provide written informed consent
Minimum age
18 Years
Maximum age
70 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)
Known hepatic cirrhosis
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
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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 design features
Phase
Phase 3
Type of endpoint/s
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
110
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC

Funding & Sponsors
Funding source category [1] 288763 0
Government body
Name [1] 288763 0
National Health & Medical Research Council
Country [1] 288763 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] 287483 0
None
Name [1] 287483 0
Address [1] 287483 0
Country [1] 287483 0
Other collaborator category [1] 277840 0
Other
Name [1] 277840 0
Queensland Institute of Medical Research Berghofer (QIMR Berghofer)
Address [1] 277840 0
300 Herston Road
Herston
Brisbane
QLD 4006
Country [1] 277840 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290604 0
Royal Brisbane and Women's Human Research Ethics Committee
Ethics committee address [1] 290604 0
Level 7 Block 7
Royal Brisbane and Women's Hospital
Butterfield Street
Herston
QLD 4029
Ethics committee country [1] 290604 0
Australia
Date submitted for ethics approval [1] 290604 0
28/01/2014
Approval date [1] 290604 0
05/03/2014
Ethics approval number [1] 290604 0
HREC/14/QRBW/35

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). Who is it for? You may be eligible to join this study if you are aged between 18 and 70 years of age and are undertaking HLA-matched allogeneic haematopoietic cell transplantation (HPCT). Trial details: Participants in this study will be randomly (by chance) divided into one of two groups. Participants in one group 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 in the second study group will receive a placebo treatment. 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 46390 0
A/Prof Glen Kennedy
Address 46390 0
Royal Brisbane and Women's Hospital
Cancer Care Services
Level 5 Joyce Tweddell Building
Herston
QLD 4029
Country 46390 0
Australia
Phone 46390 0
+61 7 3646 8111
Fax 46390 0
+61 7 3646 7371
Email 46390 0
[email protected]
Contact person for public queries
Name 46391 0
Mrs Justine Leach
Address 46391 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 46391 0
Australia
Phone 46391 0
+61 7 3646 0266
Fax 46391 0
+61 7 3646 7371
Email 46391 0
[email protected]
Contact person for scientific queries
Name 46392 0
Prof Geoff Hill
Address 46392 0
Division of Immunology
QIMR Berghofer
300 Herston Road
Brisbane
QLD 4006
Country 46392 0
Australia
Phone 46392 0
+61 7 3845 3736
Fax 46392 0
+61 7 3845 3509
Email 46392 0
[email protected]

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
SourceTitleYear of PublicationDOI
EmbaseAltered homeostatic regulation of innate and adaptive immunity in lower gastrointestinal tract GVHD pathogenesis.2017https://dx.doi.org/10.1172/JCI90592
EmbaseGranulocytes are unresponsive to IL-6 Due to an Absence of gp130.2018https://dx.doi.org/10.4049/jimmunol.1701191
EmbaseImmunomodulatory Therapies for the Treatment of Graft-versus-host Disease.2021https://dx.doi.org/10.1097/HS9.0000000000000581
EmbaseA phase 3 double-blind study of the addition of tocilizumab vs placebo to cyclosporin/methotrexate GVHD prophylaxis.2021https://dx.doi.org/10.1182/blood.2020009050
Dimensions AIEomesodermin promotes the development of type 1 regulatory T (TR1) cells2017https://doi.org/10.1126/sciimmunol.aah7152
Dimensions AIGVHD Pathogenesis, Prevention and Treatment: Lessons From Humanized Mouse Transplant Models2021https://doi.org/10.3389/fimmu.2021.723544
Dimensions AIJAK2/mTOR Inhibition Fails to Prevent Acute Gvhd Despite Reduced Th1/Th17 Cells: Final Phase II Trial Results2023https://doi.org/10.1182/blood-2023-173376
N.B. These documents automatically identified may not have been verified by the study sponsor.