Expanded Cord Blood in Patients in Need of an Allogeneic Stem Cell Transplant
Condition: Hematologic Malignancy
MeSH terms: Hematologic Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Allogeneic hematopoietic stem cell transplantation is a life-saving procedure in patients
      with blood cancers, but only 25% of transplant candidates have a sibling donor. A matched
      unrelated donor can be found for 60% of patients but this number is lower for non-Caucasians.
      Cord blood (CB), another source of stem cells, has major advantages over unrelated donors
      including immediate availability, better permissiveness in immune mismatches between donor
      and transplant recipient, better availability for non-Caucasians, and less graft versus host
      disease, a complication frequently seen after transplant which negatively affects quality of
      life. Unfortunately, the use of CB is still limited in adults because of the small number of
      stem cells. UM171, a molecule with hematopoietic stem cell expansion properties, has been
      shown to increase cord blood stem cells 13 fold. In this trial, Investigators will use UM171
      treated CB in patients who need a transplant but lack an acceptable donor.This protocol seeks
      to test the safety of CB cells expanded with UM171, and to determine the kinetics of
      engraftment as well as the minimal cord blood unit cell dose that when expanded achieves
      prompt engraftment.
    

Detailed description: 
      Investigators are proposing a phase I-II, Canadian multi-center, open-label study of UM171 ex
      vivo expanded CB transplant in 25 patients who need an allogeneic hematopoietic stem cell
      transplantation (HSCT) but lack a Human Leucocyte Antigen (HLA) matched donor.

      Investigators key primary and secondary objectives include:

        1. To establish the feasibility of expanding cord blood units for allogeneic cord blood
           transplantation.

        2. To establish the safety and identify unexpected toxicities associated with the
           transplantation of cord blood cells expanded with UM171/fed-batch culture system.

        3. To measure kinetics of neutrophil and platelet recovery.

        4. To determine minimal cord blood unit cell dose (Total Nucleated Cell (TNC)/CD34+ cells)
           that when expanded achieves prompt engraftment as a single cord transplant.

      Methodology:

      Patients with a hematologic malignancy and an indication for allogeneic HSCT who lack a
      matched unrelated donor will receive a myeloablative or submyeloablative conditioning regimen
      followed by infusion of UM171 expanded CB graft. Accrual is expected to last 18 months and
      patients will be followed for 3 years.

      Expected benefits:

      Investigators expect that expansion with UM171/fed-batch will be safe and lead to both rapid
      and sustained engraftment. This will likely decrease the high early morbidity/mortality of CB
      HSCT and improve access to transplant, especially ethnic minorities. In addition, if low cell
      dose is solved, patients will benefit from CB's lower risk of chronic (graft versus host
      disease) GVHD, a major cause of morbidity.

      .
    

Intervention name(s): Transplantation of cord blood expanded with UM171
Intervention type(s): Biological
Intervention description(s): Myeloablative or submyeloablative conditioning regimen followed by an expanded cord blood transplant
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment