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

January 20, 2017 updated by: Mariella Enoc

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rome, Italy, 00165
        • Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 20 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • nucleated cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CD34+ cells
Time Frame: up to 3 month
Target number of CD34+ cells in at least 80% of the patients
up to 3 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary and secondary graft failure
Time Frame: up to 24 months after transplantation
Cumulative incidence of primary and secondary graft failure
up to 24 months after transplantation
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
up to 24 months after 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
up to 24 months after transplantation
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
up to 12 months after the transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mariella Enoc

Investigators

  • Principal Investigator: Franco Locatelli, Prof, Bambino Gesù Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2012

Primary Completion (Actual)

September 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

January 17, 2012

First Submitted That Met QC Criteria

March 12, 2013

First Posted (Estimate)

March 13, 2013

Study Record Updates

Last Update Posted (Estimate)

January 23, 2017

Last Update Submitted That Met QC Criteria

January 20, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPBG_359.11

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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