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

Hematopoietic Stem Cell Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02327351
• Other study ID #: TCRabPID-2012
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2012
• Est. completion date: June 2018

Study information

• Verified date: February 2021
• Source: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: June 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplantation
• Immunologic Deficiency Syndromes
• Primary Immune Deficiency Disorder

Intervention

Other:
• Biological: TCR alfa beta T cell depletion

Locations

Country	Name	City	State
Russian Federation	Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT	1 year after HSCT
Secondary	Transplant Related Mortality (TRM)	transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk	24 months after transplantation
Secondary	Acute Graft Versus Host Diseases (?GVHD)	incidence of aGVHD II-IV stage estimated with cumulative incidence curve, considering graft rejection and death as competitive risks	12 months after transplantation
Secondary	Chronic Graft Versus Host Diseases (cGVHD)	incidence of cGVHD estimated with cumulative incidence curve, considering graft rejection and death as competitive risks	1 year after HSCT
Secondary	Cellular Immunological Reconstitution	Number of participants, who reached immune recovery - CD19+ lymphocytes subsets	2 years after HSCT
Secondary	Percentage of Patients With Full Donor Chimerism	Percentage of patients with full (more than 90%) donor chimerism among survivals	last follow-up
Secondary	Viral Infections After Transplant	number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT)	12 months after transplantation