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A phase I multicentre open label dose-escalation study of unrelated, Major Histocompatibility (MHC)-unmatched placenta-derived mesenchymal stem cells (MSC) in recipients of unrelated umbilical cord blood haematopoietic stem cell (HSC) transplants.MMRI CT4-MSC-UCB-001 Mater 954A

Phase 1
Conditions
Patients undergoing unrelated unmatched umbilical cord blood stem cell transplants
Cancer - Children's - Leukaemia & Lymphoma
Cancer - Leukaemia - Acute leukaemia
Cancer - Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer - Myeloma
Registration Number
ACTRN12607000279426
Lead Sponsor
Mater Medical Research Institute
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Stopped early
Sex
All
Target Recruitment
9
Inclusion Criteria

Patient is willing and has a 4/6, 5/6 or 6/6 Human Leucocyte Antigen matched unrelated donor Umbilical Cord blood graft with a cell dose >2.0 x 107 nucleated cells/kg recipient actual body weight.Patient or guardian must furnish written informed consent. Patients must have a life-threatening disease requiring treatment by unrelated cord blood transplantation Adequate cardiac function with a left ventricular ejection fraction > 45% of predicted.Adequate pulmonary function as defined as no severe or symptomatic restrictive or obstructive lung disease, and pulmonary function testing showing an Forced Expiratory Volume in 1 second >50% of predicted and a Diffuse Lung capacity for Carbon monoxide >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 or absence of hepatic fibrosis/cirrhosis.Adequate neurologic 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 techniquePatient must be Human Immunodeficiency Virus (HIV)-1 & 2 antibody, Human Immunodeficiency Virus (HIV)-1 antigen, and Human lymphotropic Virus (HTLV) I & II antibody sero-negative Patient has an Eastern Cooperative Group (ECOG) performance status of 0, 1, or a Karnofsky/ Lansky score of 70.(Use Lansky Play Scale for patients less than 16 y.o.)Patient must demonstrate ability to be compliant with medical regimen.

Exclusion Criteria

Patient has a consenting Human Luekocyte Antigens (HLA)-A-B-DRB1 identical or 5/6 HLA antigen matched related hematopoietic stem cell donor.Patient does not have a minimum Umbilical Cord Blood dose of at least 2.0 x 107 total nucleated cells/kg actual body weight (based on cryopreserved cell count of umbilical cord blood product) available from the unrelated Umbilical Cord Blood donor who is a 4/6, 5/6, or 6/6 HLA-matched.Patient has an active infection at time of transplantation.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 hematopoietic stem cell transplant or solid organ transplant

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Infusional toxicity [15minutes, 30minutes, 1 hour, 2 hours and 4 hours post infusion of MSCs];Adverse events including infections and recurrence of the underlying malignancy[Day 1 through to Day 27 on a daily basis, Day 28, Day 42 (+/- 3 days), Day 100 (+/-14 days) 12 months (+/0 14 days) and 24 months (+/-14 days)];Formation of Ectopic Tissue Foci.[Day 100, 12 and 24 months ( +/- 14 days)];Determination Of relapse[On recurrence of original malignant disease after transplantation];Human Mesenchymal Stem Cells and Umbilical Cord Blood Chimersim in Bone Marrow:[Once during days 21-28, and on days 42,100 and 1 year]
Secondary Outcome Measures
NameTimeMethod
Engraftment of neutrophils [Is defined as the day post transplant which is the first of 3 consecutive measurements when the neutrophil count is equal to, or greater than, 0.5 x 109/ul. ]; Incidence and severity of acute Graft Versus Host Disease[Day 28, day 42 and day 100 post transplantation.];Engraftment of platelets [Is defined as the day post transplant which is the first of 3 consecutive measurements when the platelet count is equal to, or greater than, 20 x 109/ul without transfusion support in the previous 7 days.]
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