Trial to Assess the Efficacy of a TCR Alfa Beta Depleted Graft in Pediatric Affected by ALL or AML and Receiving an HSCT

NCT ID: NCT01810120

Last Updated: 2017-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2016-12-31

Brief Summary

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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

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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.

Conditions

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Acute Lymphoblastic Leukemia Leukemia Acute Myeloid - AML Non-Hodgkin Lymphoma Myelodysplastic Syndromes

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TCR alfa beta depleted graft, infusion

The leukapheresis product will undergo TCR alfa beta negative selection following the standardized protocol.

Group Type EXPERIMENTAL

TCR alfa beta T cell depletion

Intervention Type BIOLOGICAL

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

Interventions

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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

Intervention Type BIOLOGICAL

Other Intervention Names

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nucleated cells

Eligibility Criteria

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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.
Minimum Eligible Age

3 Months

Maximum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mariella Enoc

OTHER

Sponsor Role lead

Responsible Party

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Mariella Enoc

Director Department of Pediatric Hematology and Oncology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Franco Locatelli, Prof

Role: PRINCIPAL_INVESTIGATOR

Bambino Gesù Children's Hospital

Locations

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Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma)

Rome, Italy, Italy

Site Status

Countries

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Italy

References

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Other Identifiers

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OPBG_359.11

Identifier Type: -

Identifier Source: org_study_id

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