Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT
Allocation: Non-Randomized Endpoint Classification: Safety/Feasibility Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment Study to assess the feasibility and safety of the infusion of a T cells receptor (TCR) alfa beta depleted graft in pediatric patients affected by malignant and non-malignant hematological disorders and receiving an Hematopoietic stem cell transplantation (HSCT) from a Human leukocyte antigen (HLA) partially matched family donor.
Acute Lymphoblastic Leukemia
Leukemia Acute Myeloid - AML
Biological: TCR alfa beta T cell depletion
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Allogeneic Hematopoietic Stem Cell Transplantation From an HLA-partially Matched Family Donor After TCR Alfa Beta Negative Selection in Pediatric Patients Affected by Hematological Disorders|
- CD34+ cells [ Time Frame: up to 3 month ] [ Designated as safety issue: Yes ]Target number of CD34+ cells in at least 80% of the patients
- Primary and secondary graft failure [ Time Frame: up to 24 months after transplantation ] [ Designated as safety issue: Yes ]Cumulative incidence of primary and secondary graft failure
- Acute and chronic GvHD [ Time Frame: up to 24 months after transplantation ] [ Designated as safety issue: Yes ]Cumulative incidence and severity of acute and chronic GvHD occurring after the transplantation
- Overall survival (OS) and disease-free survival [ Time Frame: up to 24 months after transplantation ] [ Designated as safety issue: Yes ]The overall survival (OS) and disease-free survival probability compared with a cohort of historical controls
- TCR alfa beta cells [ Time Frame: up to 12 months after the transplantation ] [ Designated as safety issue: Yes ]The immunological reconstitution of TCR alfa beta cells compared with a cohort of historical controls
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: TCR alfa beta depleted graft, infusion
The leukapheresis product will undergo TCR alfa beta negative selection following the standardized protocol.
Biological: TCR alfa beta T cell depletion
total nucleated cells from the leukapheresis product will undergo TCR alfa beta negative selection and the product of the depletion will be infused to the patient
Other Name: nucleated cells
In this study the hypothesis is that the transplantation of Peripheral blood stem cells (PBSC)selectively depleted of TCR alfa beta T lymphocytes would offers some advantages over the use of positively selected CD34+ stem cells because of the presence of other non-stem ancillary cells (in particular Natural killer (NK) and alfa beta T cells) that might have potential positive effects on the outcome of the transplant.
The clinical relevance of NK-cell alloreactivity has been demonstrated in adult patients affected by Acute myeloid leukemia (AML) and given T-cell depleted HSCT from an HLA-disparate relative where a subgroup of patients had a particularly low risk of leukemia relapse. These patients belonged to the group transplanted from a donor having NK cells that were alloreactive towards recipient targets i.e. the patient cells express HLA-class I alleles that do not share the inhibiting allelic determinants recognized by Killer immunoglobulin-like receptors (KIR) on donor NK cells. The emergence of this concept of NK-cell alloreactivity has represented a sort of revolution in the field of Haplo-identical hematopoietic stem cell translantation (haplo-HSCT), as the presence of alloreactive NK cells has been shown to positively affect the outcome of transplantation in adults and to display a Graft versus leukemia (GvL) effect that can compensate for the lack of T-specific anti-tumor effect.
The purpose of this study is to evaluate the feasibility and safety of the selective infusion of TCR alfa beta T cell depleted graft in pediatric patients affected by malignant or non malignant hematological disorders and receiving an HSCT from a partially matched family donor.
This study will provide new data on the feasibility and the safety of using a TCR alfa beta T cell depleted graft instead of fully T cell depleted graft to improve the outcome of patients receiving a haplo-HSCT for the treatment of hematological disorders.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01810120
|Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma)||Recruiting|
|Rome, Italy, 00165|
|Contact: Aurelie Bauquet firstname.lastname@example.org|
|Principal Investigator: Franco Locatelli, Prof.|
|Principal Investigator:||Franco Locatelli, Prof||Bambino Gesù Children's Hospital|