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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

Phase 1/Phase 2
3 Months
20 Years
Open (Enrolling)
Acute Lymphoblastic Leukemia, Leukemia Acute Myeloid - AML, Non-Hodgkin Lymphoma, Myelodysplastic Syndromes

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Trial Information

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

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.

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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

CD34+ cells

Outcome Description:

Target number of CD34+ cells in at least 80% of the patients

Outcome Time Frame:

up to 3 month

Safety Issue:


Principal Investigator

Franco Locatelli, Prof

Investigator Role:

Principal Investigator

Investigator Affiliation:

Bambino Gesù Children's Hospital


Italy: The Italian Medicines Agency

Study ID:




Start Date:

September 2011

Completion Date:

September 2015

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Leukemia Acute Myeloid - AML
  • Non-Hodgkin Lymphoma
  • Myelodysplastic Syndromes
  • Hematologic
  • Malignant
  • Non-Malignant
  • Allogeneic
  • Transplant
  • Non-Hodgkin Lymphoma
  • Pediatric
  • Acute lymphoblastic leukemia
  • Acute Myeloid leukemia
  • Myelodysplastic Syndromes
  • T cells receptor alfa beta
  • Hematologic Diseases
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Acute Disease