Umbilical cord blood transplantation in high-risk hematological patients using stemregenin-1 expanded hematopoietic stem cells.
A feasibility study focusing on engraftment and hematopoietic recovery.

Rationale:

Insufficient hematopoietic recovery following UCBT is considered to be primarily due to the low number of hematopoietic stem cells in UCB grafts. In-vitro stem cell expansion can be achieved by SCF, Flt3L, TPO and Stemregenin-1 (SR-1). Transplantation of double UCBT including one SR-1 expanded unit was recently demonstrated feasible and safe. The present study aims to evaluate feasibility, engraftment and recovery following transplantation of one expanded unit.



Study objectives:

 To study the feasibility of single UCBT with one ex-vivo SR-1 expanded unit

 To assess side effects and TRM after single UCBT with one expanded unit

 To assess engraftment and engraftment kinetics; to evaluate immune reconstitution, acute and chronic GVHD, chimerism, toxicity, progression-free survival and overall survival after single UCBT with one expanded unit.



Intervention:

Patients are treated with a reduced-intensity conditioning regimen, irrespective of patient age, followed by single UCBT, using one SR-1 expanded unit. Post grafting immunosuppression is performed by mycophenolate mofetil (30 days) and cyclosporine A (90 days, taper thereafter)



Duration of treatment:

Patients will be treated with a conditioning regimen during 7 days, followed by transplantation. Subsequent immunosuppression may take up to 180 days.

Patients will be followed until 5 years after registration

Expected duration of accrual: 1 year

Main study endpoint:

Feasibility as defined by, and to be achieved in ≥ 80% of (evaluable) patients:

1. SR-1 mediated expansion, resulting in > 20-fold expansion of CD34+ cells, and

2. effective hematopoietic (neutrophils > 0.5 x 109/L) engraftment within 30 days upon transplantation


Benefit and nature and extent of the burden and risks associated with participation

Benefits for individual patients may include a faster and better hematopoietic recovery, less opportunistic infections after transplantation and less graft versus host disease as compared to double UCBT

Risks of participation include graft failure and autologous recovery

Planned interim analysis and DSMB

An interim analysis will take place after the first 5 patients have been included and are found to be eligible and will be discussed with the DSMB.

 At entry: within 30 days before start of treatment

 After 1, 2, 3, 6, 12 and 24 months after transplantation and yearly therafter

Patients are treated with a reduced-intensity conditioning regimen, irrespective of patient age, followed by single UCBT, using one SR-1 expanded unit. Post grafting immunosuppression is performed by mycophenolate mofetil (30 days) and cyclosporine A (90 days, taper thereafter)1.