Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells
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.
Other: Ex vivo expanded cord blood cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Clinical Ex Vivo Expansion of Human Umbilical Cord Blood Stem and Progenitor Cells: A Pilot Trial in Collaboration With the Massachusetts Institute of Technology|
- Safety [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]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).
- Engraftment [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]Neutrophil engraftment (ANC>500/ul) in subjects as demonstrated by number of subjects with engraftment <=21 days.
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Other: Ex vivo expanded cord blood cells
- Clinical transplantation of two cord blood units: one ex vivo expanded while another unmanipulated unit to function as a back-up.
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.
- 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.
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.
|Contact: William YK Hwang, MBBS, FRCP||+65 email@example.com|
|Contact: Yvonne SM Loh, MBBS, MRCP||+65 firstname.lastname@example.org|
|Singapore General Hospital||Recruiting|
|Singapore, Singapore, 169608|
|Contact: William YK Hwang, MBBS, FRCP +65 63214625 email@example.com|
|Contact: Yvonne SM Loh, MBBS, MRCP +65 63214855 firstname.lastname@example.org|
|Principal Investigator: William YK Hwang, MBBS, FRCP|
|Sub-Investigator: Yeow T Goh, MBBS, MMed|
|Sub-Investigator: Yeh C Linn, MBBS|
|Sub-Investigator: Yvonne SM Loh, MBBS, MRCP|
|Sub-Investigator: Xiubo Fan, PhD|
|Sub-Investigator: Pak Y Chu, PhD|
|Sub-Investigator: Aloysius Ho, MBBS, FRCP|
|Sub-Investigator: Colin P Diong, MBBS, MRCP|
|Sub-Investigator: Mickey BC Koh, MBBS, FRCPath|
|Principal Investigator:||William YK Hwang, MBBS, FRCP||Singapore General Hospital|