Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT
Condition: Acute Lymphoblastic Leukemia; Leukemia Acute Myeloid - AML; Non-Hodgkin Lymphoma; Myelodysplastic Syndromes
MeSH terms: Leukemia; Lymphoma, Non-Hodgkin; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): TCR alfa beta T cell depletion
Intervention type(s): Biological
Intervention description(s): 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 intervention name(s): nucleated cells
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hematologic; Malignant; Non-Malignant; Allogeneic; Transplant; Non-Hodgkin Lymphoma; Pediatric; Acute lymphoblastic leukemia; Acute Myeloid leukemia; Myelodysplastic Syndromes; T cells receptor alfa beta