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

This study is currently recruiting participants.
Verified March 2013 by Bambino Gesù Hospital and Research Institute
Sponsor:
Information provided by (Responsible Party):
Franco Locatelli, Bambino Gesù Hospital and Research Institute
ClinicalTrials.gov Identifier:
NCT01810120
First received: January 17, 2012
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Leukemia Acute Myeloid - AML
Non-Hodgkin Lymphoma
Myelodysplastic Syndromes
Biological: TCR alfa beta T cell depletion
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Bambino Gesù Hospital and Research Institute:

Primary Outcome Measures:
  • CD34+ cells [ Time Frame: up to 3 month ] [ Designated as safety issue: Yes ]
    Target number of CD34+ cells in at least 80% of the patients


Secondary Outcome Measures:
  • Primary and secondary graft failure [ Time Frame: up to 24 months after transplantation ] [ Designated as safety issue: Yes ]
    Cumulative incidence of primary and secondary graft failure

  • Acute and chronic GvHD [ Time Frame: up to 24 months after transplantation ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    The immunological reconstitution of TCR alfa beta cells compared with a cohort of historical controls


Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   3 Months to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01810120

Locations
Italy
Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma) Recruiting
Rome, Italy, 00165
Contact: Aurelie Bauquet       aurelie.bauquet@opbg.net   
Principal Investigator: Franco Locatelli, Prof.         
Sponsors and Collaborators
Franco Locatelli
Investigators
Principal Investigator: Franco Locatelli, Prof Bambino Gesù Children's Hospital
  More Information

Publications:

Responsible Party: Franco Locatelli, Director Department of Pediatric Hematology and Oncology, Bambino Gesù Hospital and Research Institute
ClinicalTrials.gov Identifier: NCT01810120     History of Changes
Other Study ID Numbers: OPBG_359.11
Study First Received: January 17, 2012
Last Updated: March 12, 2013
Health Authority: Italy: The Italian Medicines Agency
European Union: European Medicines Agency

Keywords provided by Bambino Gesù Hospital and Research Institute:
Acute lymphoblastic leukemia
Acute Myeloid leukemia
Hematologic
Malignant
Non-Malignant
Allogeneic
Transplant
Non-Hodgkin Lymphoma
Pediatric
Myelodysplastic Syndromes
T cells receptor alfa beta

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Hematologic Diseases
Lymphoma
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on April 17, 2014