Intrabone Infusion of Cord Blood in Adults With Hematological Malignancies (IBCB)
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.
Procedure: Intrabone cord blood infusion
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Intrabone Infusion of Cord Blood Hemopoietic Stem Cells in Adult Patients With High Risk Haematological Malignancies.|
- Proportion of transplanted patients with successful engraftment at day +42 [ Time Frame: Within the first 42 days ] [ Designated as safety issue: Yes ]
- Clinical response with the analysis of global survival, survival without relapse, relapse incidence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Acute and chronic GVHD incidence [ Time Frame: For acute GVHD 100 days; for chronic GVHD 1 year ] [ Designated as safety issue: No ]
- Infection incidence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Chimerism study on selected populations (myeloid, lymphoid, NK) [ Time Frame: 30, 60, 100 days, 6 months and 1 year ] [ Designated as safety issue: No ]
- Studies on immunological reconstitution [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: Intrabone cord blood infusion
All adults patients with hematological malignancies, lacking a HLA matched donor but with a HLA compatible CB unit, fulfilling the inclusion criteria, will undergo to intrabone HSC infusion of CB.
Procedure: Intrabone cord blood infusion
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
Cyclosporine 1 mg/kg since day -7 to +120, Mycophenolate 15 mg kg x 2 since day +1 to +27
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.
|Contact: Francesca Bonifazi, MDfirstname.lastname@example.org|
|Contact: Maddalena Tonioli, PhDemail@example.com|
|Hematology Institute "L. and A. Seràgnoli", S. Orsola-Malpighi University Hospital||Recruiting|
|Bologna, Italy, 40138|
|Contact: Francesca Bonifazi, MD +39-051-636-3835/3799 firstname.lastname@example.org|
|Contact: Maddalena Tonioli, PhD +39-051-636-3799 email@example.com|
|Principal Investigator: Francesca Bonifazi, MD|
|Principal Investigator:||Francesca Bonifazi, MD||S. Orsola-Malpighi University Hospital|