Clinical trial NCT01810120: Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia
Leukemia Acute Myeloid - AML
Non-Hodgkin Lymphoma
Myelodysplastic Syndromes
Keywords: Hematologic
Malignant
Non-Malignant
Allogeneic
Transplant
Non-Hodgkin Lymphoma
Pediatric
Acute lymphoblastic leukemia
Acute Myeloid leukemia
Myelodysplastic Syndromes
T cells receptor alfa beta
Lead sponsor: Bambino Gesù Hospital and Research Institute
Sponsor class: OTHER
First posted: 2013-03-13
Enrollment: 30
Sex: ALL
Minimum age (years): 3
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: CD34+ cells
timeFrame: up to 3 month
Secondary outcomes:
measure: Primary and secondary graft failure
timeFrame: up to 24 months after transplantation
measure: Acute and chronic GvHD
timeFrame: up to 24 months after transplantation
measure: Overall survival (OS) and disease-free survival
timeFrame: up to 24 months after transplantation
measure: TCR alfa beta cells
timeFrame: up to 12 months after the transplantation
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma)
Study officials:
affiliation: Bambino Gesù Children's Hospital
name: Franco Locatelli, Prof
role: PRINCIPAL_INVESTIGATOR
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