Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT
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|ClinicalTrials.gov Identifier: NCT01810120|
Recruitment Status : Completed
First Posted : March 13, 2013
Last Update Posted : January 23, 2017
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia Leukemia Acute Myeloid - AML Non-Hodgkin Lymphoma Myelodysplastic Syndromes||Biological: TCR alfa beta T cell depletion||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||January 2012|
|Actual Primary Completion Date :||September 2016|
|Actual Study Completion Date :||December 2016|
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
- CD34+ cells [ Time Frame: up to 3 month ]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 ]Cumulative incidence of primary and secondary graft failure
- Acute and chronic GvHD [ Time Frame: up to 24 months after transplantation ]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 ]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 ]The immunological reconstitution of TCR alfa beta cells compared with a cohort of historical controls
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01810120
|Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma)|
|Rome, Italy, 00165|
|Principal Investigator:||Franco Locatelli, Prof||Bambino Gesù Children's Hospital|