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TCR Alpha/Beta Depletion for HSCT From Haploidentical and Unrelated Donors in the Treatment of PID

Primary Purpose

Primary Immune Deficiency Disorder, Hematopoietic Stem Cell Transplantation

Status
Completed
Phase
Phase 2
Locations
Russian Federation
Study Type
Interventional
Intervention
Biological: TCR alfa beta T cell depletion
Sponsored by
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immune Deficiency Disorder

Eligibility Criteria

1 Month - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged ≥ 1 months and < 19 years
  • Patients diagnosed with Primary Immunodeficiency Diseases eligible for an allogeneic transplantation and lacking a related HLA-matched donor
  • Lansky/Karnofsky score > 40, WHO > 4
  • Signed written informed consent

Exclusion Criteria:

  • 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%)
  • Serious concurrent uncontrolled medical disorder
  • Pregnant or breast feeding female patient
  • Lack of parents' informed consent.

Sites / Locations

  • Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TCR alfa beta depletion

Arm Description

TCR alfa beta depleted graft, infusion. The leukapheresis product will undergo TCR alfa beta depletion following the standardized protocol.

Outcomes

Primary Outcome Measures

Overall Survival
The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT

Secondary Outcome Measures

Transplant Related Mortality (TRM)
transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk
Acute Graft Versus Host Diseases (аGVHD)
incidence of aGVHD II-IV stage estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Chronic Graft Versus Host Diseases (cGVHD)
incidence of cGVHD estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Cellular Immunological Reconstitution
Number of participants, who reached immune recovery - CD19+ lymphocytes subsets
Percentage of Patients With Full Donor Chimerism
Percentage of patients with full (more than 90%) donor chimerism among survivals
Viral Infections After Transplant
number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT)

Full Information

First Posted
December 18, 2014
Last Updated
February 9, 2021
Sponsor
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
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1. Study Identification

Unique Protocol Identification Number
NCT02327351
Brief Title
TCR Alpha/Beta Depletion for HSCT From Haploidentical and Unrelated Donors in the Treatment of PID
Official Title
Phase II/III Study of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated and Haploidentical Donors After TCR Alfa Beta Negative Selection in Pediatric Patients With Primary Immunodeficiency Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
July 2012 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Treatment Study to assess of safety and efficiency of T cells receptor (TCR) alfa beta depleted graft for hematopoietic stem cell transplantation (HSCT) from haploidentical and unrelated donors in patients with primary immunodeficiency diseases
Detailed Description
Infections, graft versus host diseases (GVHD) and associated morbidity and mortality remains significant problems after unrelated and haploidentical hematopoietic stem sell transplantation (HSCT) in patients with primary immunodeficiency diseases (PID). In this study the hypothesis is that the transplantation of TCR alfa beta depleted peripheral blood stem cells (PBSC) would offers advantages over the use of positively selected CD34+ stem cells in haploidentical HSCT and non-manipulated graft in unrelated HSCT. The purpose of this study is to evaluate the safety and efficiency of the selective infusion of TCR alfa beta T cell depleted graft in pediatric patients with PID receiving HSCT from haploidentical and unrelated donors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immune Deficiency Disorder, Hematopoietic Stem Cell Transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
98 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TCR alfa beta depletion
Arm Type
Experimental
Arm Description
TCR alfa beta depleted graft, infusion. The leukapheresis product will undergo TCR alfa beta depletion following the standardized protocol.
Intervention Type
Other
Intervention Name(s)
Biological: TCR alfa beta T cell depletion
Primary Outcome Measure Information:
Title
Overall Survival
Description
The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT
Time Frame
1 year after HSCT
Secondary Outcome Measure Information:
Title
Transplant Related Mortality (TRM)
Description
transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk
Time Frame
24 months after transplantation
Title
Acute Graft Versus Host Diseases (аGVHD)
Description
incidence of aGVHD II-IV stage estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Time Frame
12 months after transplantation
Title
Chronic Graft Versus Host Diseases (cGVHD)
Description
incidence of cGVHD estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Time Frame
1 year after HSCT
Title
Cellular Immunological Reconstitution
Description
Number of participants, who reached immune recovery - CD19+ lymphocytes subsets
Time Frame
2 years after HSCT
Title
Percentage of Patients With Full Donor Chimerism
Description
Percentage of patients with full (more than 90%) donor chimerism among survivals
Time Frame
last follow-up
Title
Viral Infections After Transplant
Description
number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT)
Time Frame
12 months after transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged ≥ 1 months and < 19 years Patients diagnosed with Primary Immunodeficiency Diseases eligible for an allogeneic transplantation and lacking a related HLA-matched donor Lansky/Karnofsky score > 40, WHO > 4 Signed written informed consent Exclusion Criteria: 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%) Serious concurrent uncontrolled medical disorder Pregnant or breast feeding female patient Lack of parents' informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexei Maschan, Professor
Organizational Affiliation
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Dmitry Balashov, MD, PhD
Organizational Affiliation
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
City
Moscow
ZIP/Postal Code
117997
Country
Russian Federation

12. IPD Sharing Statement

Citations:
PubMed Identifier
26187864
Citation
Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, Laberko A, Livshits A, Novichkova G, Maschan A. Single-Center Experience of Unrelated and Haploidentical Stem Cell Transplantation with TCRalphabeta and CD19 Depletion in Children with Primary Immunodeficiency Syndromes. Biol Blood Marrow Transplant. 2015 Nov;21(11):1955-62. doi: 10.1016/j.bbmt.2015.07.008. Epub 2015 Jul 15.
Results Reference
derived

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TCR Alpha/Beta Depletion for HSCT From Haploidentical and Unrelated Donors in the Treatment of PID

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