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Flt3 ligand protein

Cord blood cells will be expanded ex vivo using a combination of stem cell factor (SCF), thrombopoietin (TPO), Flt3 ligand and IGFBP2 with mesenchymal stromal cell (MSC) co-culture.

Ex vivo expanded cord blood cells

William YK Hwang, MBBS, FRCP

This is a pilot clinical trial to assess the feasibility and efficacy of expanding umbilical cord blood derived blood stem cells for transplantation using a combination of chemical factors and stromal co-culture. Bone marrow (BM) mesenchymal stromal cells (MSC) will be obtained from a separate bone marrow donor. One cord blood unit will be expanded by this method while another cord blood unit will be infused without manipulation. The expanded cord blood unit will help boost the initial recovery of blood counts after transplantation, though it is expected that the unexpanded cord blood unit will provide the cells which will lead to long term engraftment of blood stem cells. A third cord blood unit will be identified for standby should the cord blood unit expansion fail.

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 search).
   * 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 graft versus host disease (GVHD) and human leukocyte antigen (HLA) matching of MSC and recipient has been shown to be not important. bone marrow mesenchymal stroma cells (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 more patients.

Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells

Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells: A Pilot Trial in Collaboration With the Massachusetts Institute of Technology

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).

Neutrophil engraftment (ANC\>500/ul) in subjects as demonstrated by number of subjects with engraftment \<=21 days.

Whitehead Institute for Biomedical Research

Blood Services Group, Health Sciences Authority of Singapore

Singapore General Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells	NCT01624701	Acute Leukemia Chronic Leukemi... Myelodysplastic... Lymphoma Myeloma	Ex vivo expande...	12 Years - 60 Years	Singapore General Hospital
Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells	NCT01624701	Acute Leukemia Chronic Leukemi... Myelodysplastic... Lymphoma Myeloma	Ex vivo expande...	12 Years - 60 Years	Singapore General Hospital
Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells	NCT01624701	Acute Leukemia Chronic Leukemi... Myelodysplastic... Lymphoma Myeloma	Ex vivo expande...	12 Years - 60 Years	Singapore General Hospital

Spots Global Cancer Trial Database for ex vivo expanded cord blood cells