None listed
Conditions
Brief summary
Diseases such as Scleroderma, Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), vasculitis, Chrohn’s disease, Behcet’s disease refractory to all available therapies and in the opinion of the referring physician, HSCT is a valid therapeutic option for that patient. These patients will require an independent physician to assess the patient’s suitability for HSCT. Patients will undergo GSCF stimulated stem cell collection following chemotherapy. Patients are readmitted for autlogous transplant and will have specific high dose immunosuppresssive therapy depending on their disorder followed by stem cell re infusion
Interventions
Patients are assessed using inclusion and exclusion criteria, some of which are specific for the underlying auto-immune disease, in order to determine whether they are eligible for an Autologous Stem cell transplant. If eligible, all patients are given Cyclophosphamide 2g/m2 as per standard practice on a Saturday or Sunday, followed by G-CSF 10mcg/kg for the next 10-12 days until the following Monday when stem cells are collected. Minimum target CD34+ stem cell collection will be 2 x 10^6/kg.
Patients are assessed using inclusion and exclusion criteria, some of which are specific for the underlying auto-immune disease, in order to determine whether they are eligible for an Autologous Stem cell transplant. If eligible, all patients are given Cyclophosphamide 2g/m2 as per standard practice on a Saturday or Sunday, followed by G-CSF 10mcg/kg for the next 10-12 days until the following Monday when stem cells are collected. Minimum target CD34+ stem cell collection will be 2 x 10^6/kg. Patients will be admitted into hospital for their autologous stem cell transplant within 4-8 weeks of stem cell collection. Patients with all autoimmune diseases (except multiple sclerosis) will then undergo chemo-immunotherapy. This consists of Cyclophosphamide 50mg/kg administered via a central venous line on days -5, -4, -3, and -2. Anti-thymocyte Globulin (ATG - Horse, ATGAM) 10mg/kg will be administered on Days -6, -5, -4 and -3 after a test dose is administered on Day -6. A minimum of 2 x 10^6/kg CD34+ cells without manipulation will be infused on Day 0. Patients with multiple sclerosis will undergo BEAM therapy combined with Horse ATG (Atgam). Such a procedure is reported in the guidelines of the cooperative group European Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR). This includes administration of carmustine 300mg/m^2 on Day -6; then cytosine arabinoside 200mg/m^2 /day and etoposide 200mg/m^2 /day on Days -5, -4, -3, -2; then Melfalan 140mg/m^2 on Day -1. Reinfusion of stem cells occurs on Day 0. This is followed by methylprednisolone 5mg/Kg /day and horse antithymocyte globulin 20mg/Kg /day on Days +1 and +2. Standard supportive measures including hydration, antiemetics, and antimicrobial prophylaxis are followed as per institutional protocols.
Sponsors
St Vincent's Hospital, Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
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), who have failed at least one licensed disease modifying drug of high efficacy (currently including alemtuzumab and natalizumab) because of demonstrated lack of efficacy (as evident from relapse, MRI activity as above, or EDSS increase) after being on Disease Modifying Therapy (DMT) for at least 6 months OR in RRMS patients where the long term immunosuppressive risk on above treatment is determined to be of significance to patients morbidity/mortality (long term risk of infection, malignancy or organ failure secondary to treatment). 4. Other Auto-Immune Conditions: Diseases such as vasculitis, Chrohn’s disease, Behcet’s disease refractory to all available therapies and in the opinion of the referring physician, HSCT is a valid therapeutic option for that patient. These patients will require an independent physician to assess the patient’s suitability for HSCT.
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
Outcome results
None listed