Hematopoietic Stem Cell Transplantation, Primary Immune Deficiency Disorder
Conditions
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.
Interventions
OTHERBiological: TCR alfa beta T cell depletion
Sponsors
Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Months to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 1 year after HSCT | The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Transplant Related Mortality (TRM) | 24 months after transplantation | transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk |
| Percentage of Patients With Full Donor Chimerism | last follow-up | Percentage of patients with full (more than 90%) donor chimerism among survivals |
| Viral Infections After Transplant | 12 months after transplantation | number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT) |
| Cellular Immunological Reconstitution | 2 years after HSCT | Number of participants, who reached immune recovery - CD19+ lymphocytes subsets |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TCR Alfa Beta Depletion TCR alfa beta depleted graft, infusion. The leukapheresis product will undergo TCR alfa beta depletion following the standardized protocol.
Biological: TCR alfa beta T cell depletion | 98 |
| Total | 98 |
Baseline characteristics
| Characteristic | TCR Alfa Beta Depletion | — |
|---|---|---|
| Age, Categorical <=18 years | 98 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Age, Continuous | 4.2 years STANDARD_DEVIATION 2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Russia | 98 participants | — |
| Sex: Female, Male Female | 23 Participants | — |
| Sex: Female, Male Male | 75 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 13 / 98 |
| other Total, other adverse events | 0 / 98 |
| serious Total, serious adverse events | 17 / 98 |
Outcome results
Primary
Overall Survival
The probability of overall survival estimated by the Kaplan-Meier method at 1 year after HSCT
Time frame: 1 year after HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCR Alfa Beta Depletion | Overall Survival | 86 percentage of survival probability |
| Matched Unrelated Donor | Overall Survival | 86 percentage of survival probability |
| HLA-mismatched Related Donor | Overall Survival | 87 percentage of survival probability |
p-value: 0.9595% CI: [79, 94]Gray test
Secondary
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
Time frame: 12 months after transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCR Alfa Beta Depletion | Acute Graft Versus Host Diseases (аGVHD) | 17 percentage of cumulative incidence |
Secondary
Cellular Immunological Reconstitution
Number of participants, who reached immune recovery - CD19+ lymphocytes subsets
Time frame: 2 years after HSCT
Population: alive at a time-point 2 years after HSCT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCR Alfa Beta Depletion | Cellular Immunological Reconstitution | 67 Participants |
Secondary
Chronic Graft Versus Host Diseases (cGVHD)
incidence of cGVHD estimated with cumulative incidence curve, considering graft rejection and death as competitive risks
Time frame: 1 year after HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCR Alfa Beta Depletion | Chronic Graft Versus Host Diseases (cGVHD) | 9 percentage of cumulative incidence |
Secondary
Percentage of Patients With Full Donor Chimerism
Percentage of patients with full (more than 90%) donor chimerism among survivals
Time frame: last follow-up
Population: survivals at the last folow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCR Alfa Beta Depletion | Percentage of Patients With Full Donor Chimerism | 48 Participants |
Secondary
Transplant Related Mortality (TRM)
transplant-related mortality estimated with cumulative incidence curve, considering relapse as a competitive risk
Time frame: 24 months after transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCR Alfa Beta Depletion | Transplant Related Mortality (TRM) | 11 percentage of cumulative incidence |
Secondary
Viral Infections After Transplant
number of patients with CMV reactivation (detection of any grade of CMV viremia after HSCT)
Time frame: 12 months after transplantation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCR Alfa Beta Depletion | Viral Infections After Transplant | 50 percentage of cumulative incidence |
| Matched Unrelated Donor | Viral Infections After Transplant | 60 percentage of cumulative incidence |
p-value: 0.35Log Rank