Intrabone Infusion of Cord Blood in Adults With Hematological Malignancies
Condition: Hematological Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to evaluate the engraftment of donor hemopoiesis (proportion of
      transplanted patients with successful engraftment at day +42) in adult patients affected by
      high risk hematological malignancies after intrabone infusion of cord blood.
    

Detailed description: 
      For many hematological malignancies, hemopoietic stem cell (HSC) transplant is the only
      possible treatment. The source of HSC is often bone marrow (BM) or, in the past 10 years,
      peripheral blood cell (PBSC) mobilized by granulocyte growth factor. Transplant needs a HLA
      compatible (related or unrelated) donor. Around 10-30% of patients with indication for
      allogeneic HSC transplant are not able to undergo the procedure because of the lack of a HLA
      compatible donor. Cord blood (CB) cells represent another possible source, which needs a
      lower degree of HLA compatibility, this type of transplant, however, offers a lower number of
      HSC. For this reason, adult patients, until now, could not use this source, because of the
      not suitable number of cell per kg, of recipient body weight. Recently, in experimental
      animal models it was observed that intrabone HSC transplant allows, in the recipient,
      engraftment of donor hemopoiesis by using a 1Log (10-1) lower number of cells compared to the
      intravenous way (Yahata 2003, Castello 2004). Safety and feasibility of intrabone infusion
      was verified by two clinical studies on humans: the first was conducted by Ringden O. et al.
      in 18 patients without any evidence of collateral effects and with complete engraftment of
      donor hemopoiesis with BM as a source of HSC (Hagglund 1998); the second one was conducted by
      Frassoni et al. (Frassoni 2008) with CB as the source of HSC.

      The aim of this study is to evaluate the intrabone infusion instead of the intravenous one,
      for the HSC transplant from CB in patients with haematological malignancies when it is not
      possible to find a HLA matched donor.

      We will perform:

        -  evaluation of the engraftment kinetics;

        -  evaluation of the chimerism degree at 30, 60, 100 days, 6 months and 1 year after
           transplant;

        -  studies on immunological reconstitution and the role of the NK compartment.
    

Intervention name(s): Intrabone cord blood infusion
Intervention type(s): Procedure
Intervention description(s): Myeloablative conditioning regimen (MAC):
i.v. Busulfan 12.8 mg/kg, Cyclophosphamide 120 mg/kg, ATG-Fresenius 30 mg/kg
Reduced intensity conditioning regimen (RIC):
Tiothepa 10 mg/kg, Fludarabine 100 mg/kg, Cyclophosphamide 100 mg/kg, ATG-Fresenius 30 mg/kg
GVHD prophylaxis:
Cyclosporine 1 mg/kg since day -7 to +120, Mycophenolate 15 mg kg x 2 since day +1 to +27
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Anti-thymocyte globulin Fresenius; Busulfan; Cord blood; Cyclophosphamide; Fludarabine; Human Leucocyte Antigen; Hematopoietic Stem Cell; Hematopoietic Stem Cell Transplant; Graft-versus-Host-Disease; Graft-versus-Host-Disease prophylaxis; Intrabone infusion; Thiotepa