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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
Sponsor:
Information provided by (Responsible Party):
Mariella Enoc, Bambino Gesù Hospital and Research Institute

January 17, 2012
March 13, 2013
January 23, 2017
January 2012
September 2016   (Final data collection date for primary outcome measure)
CD34+ cells [ Time Frame: up to 3 month ]
Target number of CD34+ cells in at least 80% of the patients
Same as current
Complete list of historical versions of study NCT01810120 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT
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
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.

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.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Acute Lymphoblastic Leukemia
  • Leukemia Acute Myeloid - AML
  • Non-Hodgkin Lymphoma
  • Myelodysplastic Syndromes
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
Experimental: TCR alfa beta depleted graft, infusion
The leukapheresis product will undergo TCR alfa beta negative selection following the standardized protocol.
Intervention: Biological: TCR alfa beta T cell depletion

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
Same as current
December 2016
September 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients aged ≥ 3 months and < 21 years
  • Patients diagnosed with malignant hemopathies (Acute Lymphoblastic leukemia (ALL), Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL)) in complete morphological remission or Myelodysplastic Syndromes (MDS), Solid Tumors or non malignant hematological disorders (SCID, Acquired and Congenital Aplastic Anemia, other Primary Immunodeficiencies, Life-threatening Cytopenia) eligible for an allogeneic transplantation and lacking a related or unrelated HLA-matched donor
  • Patients displaying an HLA-partially matched family donor
  • Lansky/Karnofsky score > 40, WHO > 4
  • Signed written informed consent

Exclusion Criteria:

  • Grade >II acute GvHD or chronic extensive GvHD at the time of inclusion
  • Patient receiving an immunosuppressive treatment for GvHD treatment at the time of inclusion
  • Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 ml / min)
  • Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%)
  • Current active infectious disease (including positive HIV serology or viral RNA)
  • Serious concurrent uncontrolled medical disorder
  • Pregnant or breast feeding female patient
  • Lack of parents' informed consent.
Sexes Eligible for Study: All
3 Months to 20 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
 
NCT01810120
OPBG_359.11
No
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Mariella Enoc, Bambino Gesù Hospital and Research Institute
Mariella Enoc
Not Provided
Principal Investigator: Franco Locatelli, Prof Bambino Gesù Children's Hospital
Bambino Gesù Hospital and Research Institute
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP