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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Date data sharing statement initially provided
Type of registration
Prospectively registered

Titles & IDs
Public title
Autologous Haematopoietic Stem Cell Transplantation for highly active treatment resistant multiple sclerosis.
Scientific title
A study to evaluate the safety of Autologous Haematopoietic Stem Cell Transplantation in patients with highly active treatment resistant multiple sclerosis.
Secondary ID [1] 297456 0
MSNI 2019.01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing Remitting Multiple Sclerosis 311640 0
Condition category
Condition code
Neurological 310263 310263 0 0
Multiple sclerosis
Inflammatory and Immune System 310264 310264 0 0
Autoimmune diseases

Study type
Description of intervention(s) / exposure
Autologous Haematopoietic Stem Cell Transplantation
Participants are assessed using inclusion and exclusion criteria specific for highly active, treatment resistant multiple sclerosis in order to determine whether they are eligible for an Autologous Stem cell transplant as part of the study.
Participants will undergo stem cell collection following intravenous infusion 2g/m2 cyclophosphamide. Intravenous fluids 0.9% Normal Saline(one litre every 6 hours) and mesna (dose 3g/m2) over 5 hours commencing one hour prior to cyclophosphamide, will be prescribed to run concurrently as per current standard practice in the Haematology Unit for malignant conditions. The intravenous fluids will run for 24 hours. This dose of Cyclophosphamide is given as a day patient in day oncology HOC unit (unless admission is determined to be necessary). Other supportive medications eg. anti-emetics as per local guidelines
From day 5 onwards daily GCSF 5mcg/kg twice daily for at least 7 days will be administered sub-cutaneously. The maximum duration for GCSF is 9 days. The duration of GCSF is determined by the level of stem cells in the blood.

Haematopoietic stem cells will then be collected and cryopreserved as per standard operating procedures in the Haematology Department.
Within 4-8 weeks from the collection of stem cells, the participant is hospitalized for the immune ablative and transplantation procedure. The timing of the transplantation procedure is determined by participant health and wellbeing, and availability of resources.The immune ablative regime consists of cyclophosphamide 50mg/kg (total of 200mg/kg) from day -5 to day -2 before transplantation, and rabbit antithymocyte globulin ATG (Thymoglobuline®) 0.5mg/kg intravenous infusion on day -5, 1.0mg/kg on day -4 and 1.5mg/kg pm days -3,-2 and -1. Methylprednisolone 1000mg intravenous infusion is to be infused 30minutes prior to rabbit ATG infusions. An additional 250mg of methylprednisolone should be used in the setting of ATG induced fever. Give mesna IV (40% of the cyclophosphamide dose) in 100 mL of normal saline over 30 minutes before the infusion of cyclophosphamide. Then commence mesna (120% of cyclophosphamide dose) in 1 litre of normal saline over 24 hours at the same time as cyclophosphamide, to finish 24 hours after the last dose of cyclophosphamide (on D-5, D-4, D-3 and D-2).
The collection and transplantation procedures will be performed as per The Alfred hospital's Standard of Care in the Haematology Department ward under the care of Haematologists, and haematology trained nursing staff. The minimum target dose of stem cells is 2 x 10^6 cells. The cells are administered by intravenous infusion.
Intervention code [1] 313711 0
Treatment: Other
Comparator / control treatment
No control group
Control group

Primary outcome [1] 319151 0
The primary objective of the cohort study is to assess the safety, as measured by transplant related mortality at Day 100 (defined as death in the first 100 days not due to MS)
Timepoint [1] 319151 0
Day 100 post transplant
Primary outcome [2] 319321 0
To assess the efficacy of HSCT as measured by (a) mean time to first relapse (clinical and MRI), (b) mean time to 3 and 6 month sustained change in EDSS and (c) mean annualised relapse rate in participants with multiple sclerosis refractory to standard therapies.
Timepoint [2] 319321 0
Month 60
Secondary outcome [1] 367138 0
To assess tolerability of the autograft between d100 and d365, particularly with respect to infectious sequelae. This will be assessed by monitoring the occurrence of infectious sequelae as adverse events
Timepoint [1] 367138 0
Day 365 post transplant

Key inclusion criteria
1. Male and female participants aged 18-60 with MS (2017 revised McDonald criteria)
2. Expanded Disability Status Scale (EDSS) score between 0 and 6
3. Highly active RRMS despite continuing to use conventional treatment for RRMS within the past 2 years.
Definition of ‘highly active’ RRMS
1. Greater than or equal to 1 severe relapses (Change in EDSS greater than or equal to 1 or 0.5 for those with pre relapse EDSS greater than or equal to 5.5) (or documented changes in neurological examination consistent with these magnitudes) and/or incomplete recovery from clinically significant relapses within the last 12 months
2. Greater than or equal to 1 gadolinium-positive (Gd+) lesion of diameter greater than or equal to 3 mm on MRI within the past 6 months.
3. Accumulation of any new T2 lesions on follow up MRI scans

1. Change in EDSS greater than or equal to 1 or 0.5 for those with pre relapse EDSS greater than or equal to 5.5)
2. evidence of new MRI activity either T1 or T2 performed on follow up MRI scans
4. Neurologically stable participants with no evidence of relapse for at least 30 days prior to study entry into the treatment period.
5. Females of childbearing potential must
a. have a negative pregnancy test at baseline prior to entry into the treatment period
b. use simultaneously two forms of effective contraception (either i.e partner) during and for 3 months after HSCT
c. females that are either post-menopausal for 12 months prior to entry into the treatment period or surgically sterile (through hysterectomy or bilateral oophorectomy) are not required to use birth control.
6. Able to provide informed consent and the absence of mental and cognitive deficits which can interfere with the capability of providing the informed consent for participation in the study prior to the Screening.
Minimum age
18 Years
Maximum age
60 Years
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
1. Participants with a non-relapsing form of MS (primary or secondary progressive MS)
2. Participants with any medically unstable condition, as assessed by the primary treating physician.
3. Participants with any of the following cardiovascular conditions:
a) history of cardiac arrest;
b) myocardial infarction within the past 6 months prior to enrolment or with current
unstable ischemic heart disease
c) cardiac failure at time of Screening (Class III, according to New York Heart
Association Classification) or any severe cardiac disease as determined by the
d) Left Ventricular (LV) ejection fraction < 45%
e) hypertension, not controlled by prescribed medications
4. Participants with any of the following pulmonary conditions:
a) severe respiratory disease or pulmonary fibrosis;
b) tuberculosis, except for history of successfully treated tuberculosis or history of
prophylactic treatment after positive PPD skin reaction
c) abnormal chest x-ray suggestive of active pulmonary disease;
d) abnormal Pulmonary Function Tests: FEV1, FVC values lower than 70% of
predicted, DLCO values lower than 60% of predicted.
5. Participants with any of the following hepatic conditions
a) known history of alcohol abuse, chronic liver or biliary disease
b) total bilirubin greater than the upper limit of the normal range, unless in context of
Gilbert’s syndrome
c) conjugated bilirubin greater than the upper limit of the normal range
d) AST, ALT greater than 2 times the upper limit of the normal range
e) alkaline phosphatase (AP) greater than 1.5 times the upper limit of the normal
f) gamma-glytamyl-transferase (GGT) greater than 3 times the upper limit of the normal
6. Participants with abnormal laboratory values
a) serum creatinine >150 µmol/L.
b) white blood cell (WBC) count <3.5x109/L or lymphocyte count <0.8x109/L
7. Participants with any of the following neurological or psychiatric conditions
a) history of substance abuse (drug or alcohol) or any other factor (i.e., serious
psychiatric condition) that may interfere with the subject’s ability to cooperate and
comply with the study procedures
b) progressive neurological disorder, other than MS, which may affect participation in
the study or require the use of medications not allowed by the protocol.
8. Participants unable to undergo MRI scans, including history of severe hypersensitivity
to gadolinium
9. Participation in any clinical research study evaluating another investigational drug or
therapy within 6 months prior to baseline.
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and
11. Participants unwilling to use effective contraception

Study design
Purpose of the study
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Open label
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
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 13205 0
The Alfred - Prahran
Recruitment postcode(s) [1] 25761 0
3004 - Melbourne
Recruitment postcode(s) [2] 25762 0
3004 - Prahran

Funding & Sponsors
Funding source category [1] 302027 0
Name [1] 302027 0
Alfred Health
Address [1] 302027 0
55 Commercial Road
Melbourne 3004 VIC
Country [1] 302027 0
Primary sponsor type
Alfred Health
55 Commercial Road
Melbourne 3004 VIC
Secondary sponsor category [1] 301823 0
Name [1] 301823 0
Address [1] 301823 0
Country [1] 301823 0

Ethics approval
Ethics application status
Ethics committee name [1] 302706 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 302706 0
55 Commercial Road
Melbourne 3004 VIC
Ethics committee country [1] 302706 0
Date submitted for ethics approval [1] 302706 0
Approval date [1] 302706 0
Ethics approval number [1] 302706 0

Brief summary
We propose to study the benefits and risks of Autologous Haematopoetic Stem Cell Transplant (AHSCT) in people who have an aggressive form of MS not controlled by conventional treatment. Participants will have AHSCT at The Alfred hospital, and they will be closely monitored for 5 years post the transplant to ensure their safety, and also level of Multiple Sclerosis disease activity.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 91118 0
Dr Cassie Nesbitt
Address 91118 0
The Alfred Hospital
55 Commercial Road
Melbourne 3004 VIC
Country 91118 0
Phone 91118 0
+61 3 9903 8662
Fax 91118 0
Email 91118 0
Contact person for public queries
Name 91119 0
Dr Cassie Nesbitt
Address 91119 0
The Alfred Hospital
55 Commercial Road
Melbourne 3004 VIC
Country 91119 0
Phone 91119 0
+61 3 9903 8662
Fax 91119 0
Email 91119 0
Contact person for scientific queries
Name 91120 0
Dr Cassie Nesbitt
Address 91120 0
The Alfred Hospital
55 Commercial Road
Melbourne 3004 VIC
Country 91120 0
Phone 91120 0
+61 3 9903 8662
Fax 91120 0
Email 91120 0

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results