A Single Centre Phase II Study Of Haematopoietic Stem Cell Transplantation (HSCT) for Severe Auto-Immune Diseases.

Phase 2

Recruiting

• Conditions: Auto Immune disorders; Inflammatory and Immune System - Other inflammatory or immune system disorders; Musculoskeletal - Other muscular and skeletal disorders; Neurological - Multiple sclerosis

• Registration Number: ACTRN12613000339752
• Lead Sponsor: St Vincent's Hospital, Sydney

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03-27
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Adequate organ function as measured by:
Cardiac LV Ejection Fraction greater than 45%, total Lung Capacity greater than 60%, Pulmonary artery pressure greater than 50mmHg, DLCO greater than or equal to 50%.
Negative serology for HBV, HCV and HIV.
Negative pregnancy test.
Able to provide informed consent and the absence of mental and cognitive deficits which can interfere with the capability of providing the informed consent.
Absence of severe chronic infection.
Severe auto-immune disease less than 7 years duration (excluding Multiple Sclerosis) OR Multiple sclerosis of any duration unresponsive to multiple standard therapies including corticosteroids.
HSCT deemed best high-intensity immunotherapeutic treatment in the opinion of the referring physician.

Sperm collection or ova cryopreservation is to be offered prior to HSCT in those of child-bearing age

Specific Inclusion Criteria for each disease:
1.Systemic Sclerosis:
Early, rapidly progressive inflammatory diffuse scleroderma with truncal skin involvement and/or involving lungs and/or heart (myocarditis) which has failed to stabilize with anti-rheumatic agents. All patients with severe Systemic Sclerosis will undergo right catheterisation prior to cyclophosphamide mobilisation to assess for pulmonary artery pressure. Ideally patients will also have signs of ongoing disease-related inflammation immediately prior to ASCT. Early disease is defined as disease in which the timing from second symptom onset to ASCT was 7 years or less

2. Systemic lupus erythematosus (SLE):
Diagnosis according to ACR-criteria with antinuclear antibodies positive on at least two successive tests at three months interval plus disease duration less than 7 years since the diagnosis or first time of intensive immunosuppressive drugs. Unresponsive to multiple therapies including at least 6 months of the best standard local therapy using prednisone, intravenous cyclophosphamide or mycophenolate mofetil either alone or successively with or without anti CD 20 (Rituximab). Major organ damage (eg: cerebritis, nephritis, pulmonary, cardiac or skin vasculitis) is present despite optimal immunosuppression.

3. Multiple Sclerosis (MS):
I. Diagnosis of relapsing remitting MS (RRMS) made by a Neurologist according to
the 2010 revised McDonald’s criteria
II EDSS score 0-6.5 NB: EDSS of 6.5 (this corresponds to able to walk, needing at most bilateral assistance to walk 20m without resting). Patients with an EDSS of 0-2 will require a second independent physician to assess the patient’s suitability for HSCT
III Disease duration of at least 15 years from diagnosis of MS
IV New MRI activity within last 12 months: Inflammatory active MS as defined by at least 1 Gd+ (>3mm) lesion (off steroids for one month) or at least 2 new T2 lesions on MRI within the last 12 months, compared to a reference scan not older than 36 months and preferably within the last 24 months from the date of eligibility review OR
a history of highly active disease, as determined by previous MRI prior to commencement of high efficacy treatment (alemtuzumab and/or natalizumab), in patients where the long term immunosuppresive risk on treatment is determined to be of significance to patients morbidity/mortality (long term risk of infection, malignancy or organ failure secondary to treatment). Confirmation regarding suitability for HSCT from an external neurologist will be required in this case.
V Relapsing-remitting MS (RRMS), wh

Exclusion Criteria

- If specific auto immune disorders does not meet the individual eligibility criteria.
- Any patient on the study treatment arm deemed not suitable for transplant by HSCT specialist
- Any patient unable to understand the purpose and risks of the study
- Patients deemed by their treating neurologist to have entered phase of secondary progressive

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Safety, as measured by transplant related mortality (TRM) by day 100. This is defined as death upto 100 days post transplant, not due to the original disease. [ day 100];Efficacy of HSCT in various auto-immune conditions that are refractory to standard therapies. This will be assessed using standardised clinical and laboratory criteria, specific for each auto-immune disease.[ 3 months, 6months, 12months then yearly up to 5 years]