None listed
Conditions
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.
Interventions
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 MS
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)
Sponsors
Mater Medical Research Institute
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 60 Years
Healthy volunteers
Yes
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.
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
Outcome results
None listed