Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells: A Pilot Trial in Collaboration With the Massachusetts Institute of Technology
1. Clinical transplantation of two cord blood units: one ex vivo expanded while another
unmanipulated unit to function as a back-up.
2. Ten patients will be selected from those for whom:
- Allogeneic haematopoietic stem cell transplant is indicated (see details)
- No matched sibling or matched unrelated donor is available quickly enough for the
transplant (no fully matched donor found within 1 month of initiation of donor
search or donor found but not available for donation within 3 months of donor
- At least three unrelated donor cord blood unit can be identified with less than 2
antigens mismatches with the patient but with insufficient cell dose to meet the
patient's requirements. If clinical efficacy of this protocol is demonstrated, we
will proceed to a multicentre clinical trial with more patients.
3. The investigators will obtain haplo-identical MSC from the bone marrow of
sibling/parent/offspring of the patient. Although there will be some MSC co-infused
with the cord blood cells, this has been shown to be safe in trials of MSC given for
patients with GVHD and human leukocyte antigen (HLA) matching of MSC and recipient has
been shown to be not important. BM-MSCs derived from related donor bone marrow with a
minimum of 2/6 HLA match have been safe for use in patients.1 If the haplo-identical
MSC donor is not available, matched unrelated donor MSC would also be used.
4. Efficacy will be assessed by the following and compared to published literature as well
as historical controls:
- Neutrophil and platelet engraftment
- Post transplant 100-day mortality
- Overall and progression-free survival If clinical efficacy of this protocol is
demonstrated, the investigators will proceed to a multicentre clinical trial with
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of subjects with infusional toxicities (including fever, renal dysfunction within 72 hours of infusion) and potential immunologic competition (absent chimerism of donor cells by 21 days post transplantation).
William YK Hwang, MBBS, FRCP
Singapore General Hospital
Singapore: Health Sciences Authority