Autologous Stem Cell Transplant in Neuro-Inflammatory diseases other than multiple sclerosis
A phase II interventional study: Safety and tolerability of Haematopoietic Stem Cell Transplantation for neuro-inflammatory disease
The Alfred- Melbourne
5 participants
Oct 30, 2022
Interventional
Conditions
Summary
Autologous haematopoietic stem cell transplantation (AHSCT) is a procedure that is typically used to give high doses of chemotherapy to patients with blood cancers, followed by stem cell infusion, so that a new blood and immune system can regrow. Stem cells are collected from the blood following stimulation with intravenous cyclophosphamide chemotherapy and granulocyte colony stimulating factor (GCSF) injections. Patients are then admitted into hospital to receive high doses of chemotherapy that intensely suppresses their immune system. Subsequently they have their stem cells transfused to re-grow a new immune system and provide protection from the toxic effects of the chemotherapy. It takes about 14 days for the new stem cells to grow and all patients are monitored carefully over the subsequent months and years to see if the immunosuppression controls their auto-immune disease. Over the last 15 years AHSCT become much safer, and evidence has accumulated suggesting a proportion of patients with severe autoimmune conditions will respond to AHSCT. Often these patients had prolonged remissions of their AID. In well selected patients there is a possibility to establish a prolonged period of disease remission.
Eligibility
Inclusion Criteria26
- Age 18-65
- o Age 65-70 (may be considered only if HCT-CI (Haemopoietic cell transplantation – comorbidity index) <3 and deemed fit both physically and cognitively by at least two investigators)
- Adequate organ function as measured by:
- o Cardiac Left Ventricle Ejection Fraction greater than 45%
- o Total Lung Capacity of at least 60%
- o DLCO/VA (Diffusing Capacity Of The Lungs For Carbon Monoxide) of at least 50%.
- o Negative serology for active Hepatitis B, active Hepatitis C and Human Immunodeficiency Virus.
- o Negative CT skeletal survey in patients with Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and a para-protein
- o Serological assessments of haematology, liver, kidney and thyroid function reviewed by transplant physician and specialty input sought were required.
- No evidence of chronic infection or significant systemic illness where a treating specialist has concerns about HSCT.
- Clearance from treating physician in the case of prior or co-existent malignancy
- No current history of substance abuse (drug or alcohol) or other factor (eg: serious psychiatric impairment) that may interfere with patient’s ability to comply with the study procedure and follow up.
- Negative pregnancy test.
- Sperm collection or ova cryopreservation is to be offered prior to HSCT in those of child-bearing age.
- Patients must agree to use a form of effective contraception (either i.e. partner) during and for 3 months after HSCT (females that are either post-menopausal for 12 months prior to randomization or surgically sterile [through hysterectomy or bilateral oophorectomy] are not required to use birth control).
- Able to provide informed consent and the absence of mental and cognitive deficits which can interfere with the capability of providing the informed consent.
- AHSCT deemed an appropriate high-intensity immunotherapeutic treatment in the opinion of the referring physician.
- Published data to support the role of AHSCT for the disease.
- Suitability for AHSCT will be determined by a multidisciplinary HSCT panel including a neurologist and haematologists/transplant physicians.
- If suitability is contended an expert opinion from and alternate national or international centre involved in AHSCT for AID may be sought.
- Any patient on the study treatment arm deemed not suitable for transplant by a consensus of HSCT specialists as determined at the HSCT MDT.
- Any patient unable to understand the purpose and risks of the study or adhere to the post-transplant management including medication adherence and appointment attendance.
- Patients with a predominately progressive form of disease.
- Patients where mimics have not been adequately excluded.
- Patients unable to undergo MRI scans.
- Patients with advanced NID where the risks of transplant are deemed to outweigh potential benefits.
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Interventions
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 via subcutaneous injection. 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.
Locations(1)
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ACTRN12622001186741