Clinical trial NCT02327351: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Primary Immune Deficiency Disorder
Hematopoietic Stem Cell Transplantation
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
First posted: 2014-12-30
Enrollment: 98
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Survival
timeFrame: 1 year after HSCT
Secondary outcomes:
measure: Transplant Related Mortality (TRM)
timeFrame: 24 months after transplantation
measure: Acute Graft Versus Host Diseases (аGVHD)
timeFrame: 12 months after transplantation
measure: Chronic Graft Versus Host Diseases (cGVHD)
timeFrame: 1 year after HSCT
measure: Cellular Immunological Reconstitution
timeFrame: 2 years after HSCT
measure: Percentage of Patients With Full Donor Chimerism
timeFrame: last follow-up
measure: Viral Infections After Transplant
timeFrame: 12 months after transplantation
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
Study officials:
affiliation: Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
name: Alexei Maschan, Professor
role: STUDY_CHAIR
affiliation: Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
name: Dmitry Balashov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.