Non-severe combined immunodeficiency inborn errors of immunity Haematological Disorders
Conditions
Interventions
There are three arms across two sites with this trial
the intervention arm, control group 1 and control group 2.
The interventional cohort (n=40) will include only children who are receiving a TCRaß-HaploSCT (because of the lack of a suitable fully matc
• Stage 1 will determine the optimum safe and effective dose of CD45RO+ memory T-cell addback.
• Stage 2 will determine whether CD45RO+ memory T-cell addback can accelerate immune reconstitution and
0.3 x 10^6/kg, 0.6 x 10^6/kg and 1.0 x 10^6/kg. Where a participant has been randomised but does not go on to receive the addback, for any reason, they will be withdrawn and an additional patient will
Sponsors
Newcastle upon Tyne Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Age
1 Months to 17 Years
Inclusion criteria
Inclusion criteria: 1. Age at least 1 month and up to 18 years at the time of scheduled transplant 2. Patients deemed clinically eligible for allogeneic HSCT for non-SCID IEI 3. No suitable conventional matched family donor#. 4. Patient has an eligible donor identified by the clinical transplant team: 4.1. Planned mismatched family or mismatched unrelated donor for TCRaß-HaploSCT (Intervention and control group 1)* OR 4.2. 10/10 HLA-matched unrelated donor for MUD HSCT (control group 2) 5. Capacity for patient or the patient’s parent or guardian to provide written informed consent 1. # Donor choice is independent of this study and will be decided by the clinical team according to best clinical practice. Generally the hierarchy of preferred donor is 10/10 matched family donor > 10/10 matched unrelated donor > mismatched family donor > mismatched unrelated donor. However, depending on the specific disorder, a family member might not be a suitable donor if they are a carrier of the genetic disease, or the underlying molecular defect is unknown.
Exclusion criteria
Exclusion criteria: 1. Lansky/Karnofsky performance score <30% 2. Ongoing active acute GvHD or chronic extensive GvHD due to previous allograft at the time of screening 3. Patient receiving an immunosuppressive treatment for GvHD due to previous allograft at time of screening 4. Presence of a medical condition indicating that survival will be dismal such as the requirement for a high setting of mechanical ventilation and severe failure of a major organ system 5. Pregnancy or breastfeeding in female patients Additional exclusion criteria for intervention group and control group 1 only (TCRaß-HaploSCT) 1. Patients with donor-specific antibodies (DSA) against the potential stem cell donor using the standard test according to the institutional guideline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The following primary outcome measures are assessed 3 months post-SCT: 1. Time to T-cell immune reconstitution defined as CD3+ T-lymphocytes = 200 cells/µL measured using flow cytometry 2. Incidence and severity of acute (Gluckberg criteria) and chronic GvHD (National Institutes of Health (NIH) consensus criteria) measured using clinical assessment 3. Time to T-cell immune reconstitution defined as CD3+ T-cells = 200 cells/µL measured using flow cytometry | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Lymphocyte/monocyte/T-cell (total, CD4+, CD8+, naive)/NK cell/B cell count measured using flow cytometry at 1, 2, 3, 4 and 5 months post-SCT 2. CMV, adenovirus, EBV and HHV6 measured in whole blood using viral polymerase chain reaction (PCR) and clinical assessment weekly during the first 90 days, at day +105, day +120 and day +180 3. Grade III-IV acute GvHD and extensive chronic GvHD according to Glucksberg criteria and NIH consensus criteria respectively measured using clinical assessment at days + 28, +56, +91, +105, +120, +180 4. Transplant-related mortality: defined as death between the day of transplantation (day 0) and the day of the event, not due to disease recurrence and considered related to transplant by the investigator measured using clinical data with death reported as an SAE 5. Overall survival: defined as survival from day 0 after HSCT to last follow-up or death; event-free survival: defined as survival without events (death, graft failure or second procedures); GvHD-free, event-free survival: defined as survival without events, Grade III-IV aGvHD or extensive chronic GvHD: all measured using clinical data with events and time of onset on death, graft failure, second procedures, acute and chronic graft-versus-host disease being recorded 6. Cumulative incidence of graft failure after HSCT measured using clinical data and Graft failure and time of onset will be recorded 7. Time to neutrophil engraftment: defined as the first of 3 consecutive days with ANC = 0.5 x 10e9/L after the first post-transplant conditioning regimen induced nadir measured using laboratory parameters from routine full blood counts at the time to first of 3 consecutive days with ANC = 0.5 x 10e9/L post-SCT 8. Time to platelet engraftment: defined as the first 3 consecutive days with platelet = 20 x 10e9/L with no platelet transfusion in at least 7 preceding days measured using laboratory parameters from routine full blood counts 9. Chimerism analysis of peripheral blood mononu | — |
Countries
United Kingdom
Contacts
Public ContactAna;Clare Alvarez Franco;Bowes
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Outcome results
None listed