Trial registered on ANZCTR


Trial ID
ACTRN12607000430437
Ethics application status
Not yet submitted
Date submitted
26/06/2007
Date registered
23/08/2007
Date last updated
23/08/2007
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 1 multicentre open label dose-escalation study of unrelated, major histocompatibility (MHC)-unmatched mesenchymals stem cells (MSC) for the treatment of steroid refractory acute graft versus host disease in recipients of allogeneic heamatopoietic stem cell transplants
Scientific title
A phase 1 multicentre open label dose-escalation study of unrelated, major histocompatibility (MHC)-unmatched mesenchymals stem cells (MSC) for the treatment of steroid refractory acute graft versus host disease in recipients of allogeneic heamatopoietic stem cell transplants
Universal Trial Number (UTN)
Trial acronym
MMRI CT5-MSC-GVHD-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Patients who have undergone a allogeneic stem cell transplant who have developed steroid refractory graft versus host disease 2169 0
Condition category
Condition code
Inflammatory and Immune System 2264 2264 0 0
Other inflammatory or immune system disorders
Cancer 2382 2382 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study has been designed as a phase I multicentre open label dose-escalation study. In addition to institutional standard-of-care for steroid-refractory acute graft-versus-host disease, patients will receive three infusions of mesenchymal stem cell (MSC) one week apart. The first 3 patients will receive an intravenous infusion of human bone marrow-derived MSC at a dose of 1 x 106 MSC/kg weekly for three consecutive weeks (days 1, 8 and 15, with day 1 being the day of the first infusion of MSC). If no serious adverse events are detected 1 week after the last MSC infusion in patient 3, patients 4, 5 and 6 will receive an intravenous infusion of human bone marrow-derived MSC at a dose of 3.3 x106 MSC/kg weekly for three consecutive weeks. If no serious adverse events are detected 1 week after the last MSC infusion in patient 6, the last 3 patients (patients 7, 8 and 9) will receive an intravenous infusion of human bone marrow-derived MSC at a dose of 10 x 106 MSC/kg weekly for three consecutive weeks. The MSC in this study will be derived from bone marrow obtained from a volunteer normal healthy donor unrelated to, and MHC-unmatched with, the recipient and with the transplanted heamatopoietic stem cells (HSCs)
Intervention code [1] 2002 0
Treatment: Other
Comparator / control treatment
There is no control arm to this study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 3282 0
Infusional toxicity
Timepoint [1] 3282 0
- 1 hour, 15 minutes post infusion, +30minutes, + 1 hour, + 2 hours and + 4 hours
Primary outcome [2] 3283 0
Adverse events including infections and recurrence of underlying malignancy
Timepoint [2] 3283 0
Baseline, Day 1 through to Day 27, Day 28, Day 42, Day 100, +12 months and + 24 months
Primary outcome [3] 3284 0
Ectopic Tissue Formation
Timepoint [3] 3284 0
Baseline, Day 1 through to Day 27, Day 28, Day 42, Day 100, +12 months and + 24 months
Secondary outcome [1] 5464 0
Response of steroid refractory acute graft versus host disease to the mesenchymal stem cell infusion
Timepoint [1] 5464 0
Baseline, Day 1 through to Day 27, Day 28, Day 42, Day 100, +12 months and + 24 months

Eligibility
Key inclusion criteria
Patient is willing and has received an allogeneic bone marrow transplant for a life-threatening disease
Patient has steroid-refractory graft-versus-host disease following the allogeneic bone marrow transplant
Patient or guardian must furnish written informed consent.
Adequate cardiac function with a left ventricular ejection fraction > 45% of predicted.
Adequate pulmonary function pre-haematopietic stem cell transplant, as defined as no severe or symptomatic restrictive or obstructive lung disease, and pulmonary function testing showing an forced expired volume in one second (FEV1) >50% of predicted and a carbon monoxide diffusin capacity (DLCO) >50% of predicted.
(Children less than 6 years of age must have normal oxygen saturation, in the opinion of the Investigator)
Adequate renal function as defined by a creatinine clearance >40% of normal.
Adequate hepatic function as defined by a total bilirubin < 2x normal except for patients with hepatic dysfunction thought due to graft versus host disease.
Adequate neurological function as defined by no evidence of a severe central or peripheral neurological abnormality.
Adequate immunologic function as defined by no evidence of active infection at the time of the transplant preparative regimen.
Female patients are not pregnant, not breast-feeding and are using adequate birth control technique
Patient must be human immunodeficiency virus (HIV)-1 & 2 antibody sero-negative
Patient must demonstrate ability to be compliant with medical regimen.
Minimum age
18 Years
Maximum age
60 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Patient has active alcohol or substance abuse within 6 months of study entry.
Patient is enrolled on another investigational agent concurrently.
Patient has any medical condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient.
Patient has had a prior haematopoietic stem cell transplant or solid organ transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Nil
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet 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
Current
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 391 0
4101
Recruitment postcode(s) [2] 392 0
2145

Funding & Sponsors
Funding source category [1] 2427 0
Charities/Societies/Foundations
Name [1] 2427 0
Inner Wheel Foundation of Australia
Address [1] 2427 0
Country [1] 2427 0
Australia
Funding source category [2] 2543 0
Charities/Societies/Foundations
Name [2] 2543 0
Inner Wheel Foundation of Australia
Address [2] 2543 0
PO Box 519 Tamworth NSW 2340
Country [2] 2543 0
Australia
Primary sponsor type
Other
Name
Mater Medical Research Institute
Address
Level 2 Aubigny Place, Raymond Terrace
South Briabsne Q 4101
Country
Australia
Secondary sponsor category [1] 2301 0
Hospital
Name [1] 2301 0
Mater Health Services
Address [1] 2301 0
Raymond Terrace South Briabsne Q 4101
Country [1] 2301 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 4280 0
MHS HREC
Ethics committee address [1] 4280 0
Ethics committee country [1] 4280 0
Australia
Date submitted for ethics approval [1] 4280 0
Approval date [1] 4280 0
Ethics approval number [1] 4280 0
Ethics committee name [2] 4281 0
Westmead HREC
Ethics committee address [2] 4281 0
Ethics committee country [2] 4281 0
Australia
Date submitted for ethics approval [2] 4281 0
Approval date [2] 4281 0
Ethics approval number [2] 4281 0
Ethics committee name [3] 4459 0
Ethics committee address [3] 4459 0
Ethics committee country [3] 4459 0
Date submitted for ethics approval [3] 4459 0
19/04/2007
Approval date [3] 4459 0
Ethics approval number [3] 4459 0

Summary
Brief summary
This is a phase I study to investigate the safety and feasibility of administering unrelated, tissue-unmatched, bone marrow-derived mesenchymal stem cells in recipients of allogeneic haematopoietic stem cell transplants who develop serious, treatment-resistant graft-versus-host disease. Such graft-versus-host disease is frequently fatal. In early studies in the USA and Europe mesenchymal stem cells appear to have a beneficial effect in this setting. No formal studies have been conducted yet in Australia.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 27667 0
Address 27667 0
Country 27667 0
Phone 27667 0
Fax 27667 0
Email 27667 0
Contact person for public queries
Name 11042 0
Sonia Hancock
Address 11042 0
Level 3 Aubigny Place
Raymond Terrace
South Brisbane QLD 4101
Country 11042 0
Australia
Phone 11042 0
07 3840 1558
Fax 11042 0
07 3840 2134
Email 11042 0
shancock@mmri.mater.org.au
Contact person for scientific queries
Name 1970 0
Professor Kerry Atkinson
Address 1970 0
Division of Cancer Services
Level 3 MAH
Rayomind Terrace
South Brisbane QLD 4101
Country 1970 0
Australia
Phone 1970 0
07 3840 3429
Fax 1970 0
07 3840 8012
Email 1970 0
kerry.atkinson@mater.org.au