Graft Failure, Hematopoietic Stem Cell Transplantation, Wiskott-Aldrich Syndrome
Conditions
Brief summary
Treatment Study to assess of safety and efficiency of conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patient with Wiskott-Aldrich syndrome.
Detailed description
Severe graft dysfunction, such as the degree of donor chimerism predominantly in the myeloid compartment is one of major problem in patients with Wiskott-Aldrich syndrome (WAS), especially after hematopoietic stem cell transplantation (HSCT) from alternative donor. It often leads to the development of severe thrombocytopenia or even transplants rejection. In this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in conditioning regimen would offers advantages due to lowing risk of mixed chimerism after HSCT. This effect is based on the fact that simultaneous use of plerixafor with G-CSF is efficient in inducing stem cell release and opening of bone marrow (BM) niches. Moreover, stem cell release probably leads to liberation of host stem cells from the anti-apoptotic effects of the BM stroma for the more powerful effect of chemotherapy. In this study, the investigators use TCR alpha/beta grafts depletion of the grafts as basic technology for HSCT from haploidentical and unrelated donors approved in Institution. Thus, the purpose of this study is to evaluate the safety and efficiency of myeloablative conditioning with Plerixafor and G-CSF as additional agents for prevention of graft failure after transplantation with TCR alpha/beta grafts depletion in patients with Wiskott-Aldrich syndrome.
Interventions
BIOLOGICALG-CSF for Conditioning before HSCT.
Mobilization of hematopoietic stem (HSC) into circulation
BIOLOGICALPlerixafor for Conditioning before HSCT.
Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment.
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 19 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged ≥ 1 months and \< 19 years * Patients diagnosed with Wiskott-Aldrich syndrome 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 * Lack of parents' informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival (EFS) | 24 months | The EFS probability compared with historical control. We mean event as patient's death, second transplantation or persistence of severe thrombocytopenia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with full/mixed donor chimerism | 12 months | Evaluation of the percentage of patients with the full/mixed donor chimerism (whole blood and CD3+ lineage). In addition, patients will be divided in accordance with % of donors cells: \>95%; 50%-95%; 10%-49%; \<10%. All data will be compared with historical control |
| Transplant related mortality (TRM) | 24 months | The TRM probability compared with historical control. |
| Severe thrombocytopenia (ST) | 24 months | The ST probability after HSCT compared with historical control |
| Overall survival (OS) | 24 months | The OS probability compared with historical control. |
| Acute Graft Versus Host Diseases (aGVHD) | 12 months | Cumulative Incidence and severity of aGVHD |
| Chronic Graft Versus Host Diseases (cGVHD) | 24 months | Cumulative Incidence and severity of cGVHD |
| Plerixafor related complications (PRC) | 2 week | PRC: severity, features, incidence |
| Autoimmune complications (AC) | 24 months | The AC probability after HSCT compared with historical control |
Countries
Russia
Contacts
Primary ContactDmitry Balashov, MD, PhD
Backup ContactMichael Maschan, Professor
Outcome results
None listed