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

Phase 2

Completed

• Conditions: Hematopoietic Stem Cell Transplantation; Primary Immune Deficiency Disorder

• Registration Number: NCT02327351
• Lead Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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.

Study Timeline

• Study Start: 2012-07
• Study First Submitted: 2014-12-18
• Study First Submitted QC: 2014-12-24
• Study First Posted: 2014-12-30
• Primary Completion: 2017-12
• Study Completion: 2018-06
• Results First Submitted: 2020-11-30
• Status Verified: 2021-02
• Results First Submitted QC: 2021-02-09
• Last Update Submitted: 2021-02-09
• Results First Posted: 2021-02-26
• Last Update Posted: 2021-02-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 98

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Chronic Graft Versus Host Diseases (cGVHD)	1 year after HSCT	incidence of cGVHD estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Percentage of Patients With Full Donor Chimerism	last follow-up	Percentage of patients with full (more than 90%) donor chimerism among survivals
Acute Graft Versus Host Diseases (аGVHD)	12 months after transplantation	incidence of aGVHD II-IV stage estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Viral Infections After Transplant	12 months after transplantation	number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT)
Transplant Related Mortality (TRM)	24 months after transplantation	transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk
Cellular Immunological Reconstitution	2 years after HSCT	Number of participants, who reached immune recovery - CD19+ lymphocytes subsets

Trial Locations

Locations (1)

Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology; 🇷🇺 Moscow, Russian Federation