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

Phase 1

Completed

• Conditions: Leukemia Acute Myeloid - AML; Myelodysplastic Syndromes; Non-Hodgkin Lymphoma; Acute Lymphoblastic Leukemia
• Interventions: Biological: TCR alfa beta T cell depletion

• Registration Number: NCT01810120
• Lead Sponsor: Mariella Enoc

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.

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2012-01-17
• Study First Submitted QC: 2013-03-12
• Study First Posted: 2013-03-13
• Primary Completion: 2016-09
• Study Completion: 2016-12
• Status Verified: 2017-01
• Last Update Submitted: 2017-01-20
• Last Update Posted: 2017-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TCR alfa beta depleted graft, infusion	TCR alfa beta T cell depletion	The leukapheresis product will undergo TCR alfa beta negative selection following the standardized protocol.

Primary Outcome Measures

Name	Time	Method
CD34+ cells	up to 3 month	Target number of CD34+ cells in at least 80% of the patients

Secondary Outcome Measures

Name	Time	Method
Primary and secondary graft failure	up to 24 months after transplantation	Cumulative incidence of primary and secondary graft failure
Acute and chronic GvHD	up to 24 months after transplantation	Cumulative incidence and severity of acute and chronic GvHD occurring after the transplantation
Overall survival (OS) and disease-free survival	up to 24 months after transplantation	The overall survival (OS) and disease-free survival probability compared with a cohort of historical controls
TCR alfa beta cells	up to 12 months after the transplantation	The immunological reconstitution of TCR alfa beta cells compared with a cohort of historical controls

Trial Locations

Locations (1)

Department of Oncology/Hematology of the Hospital Bambino Gesù (Roma); 🇮🇹 Rome, Italy