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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Plerixafor/G-CSF for HSCT conditioning | Experimental | Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| G-CSF for Conditioning before HSCT. | Biological | Mobilization of hematopoietic stem (HSC) into circulation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Event free survival (EFS) | The EFS probability compared with historical control. We mean event as patient's death, second transplantation or persistence of severe thrombocytopenia | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | The OS probability compared with historical control. | 24 months |
| Percentage of patients with full/mixed donor chimerism | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dmitry Balashov, MD, PhD | Contact | +7(495)287-6570 | 6534 | bala8@yandex.ru |
| Michael Maschan, Professor | Contact | +7(926)651-2145 | mmaschan@yandex.ru |
| Name | Affiliation | Role |
|---|---|---|
| Alexei Maschan, Professor | Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology | Study Chair |
| Dmitry Balashov | Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology | Recruiting | Moscow | 117997 | Russia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29550630 | Derived | Balashov D, Laberko A, Shcherbina A, Trakhtman P, Abramov D, Gutovskaya E, Kozlovskaya S, Shelikhova L, Novichkova G, Maschan M, Rumiantsev A, Maschan A. A Conditioning Regimen with Plerixafor Is Safe and Improves the Outcome of TCRalphabeta+ and CD19+ Cell-Depleted Stem Cell Transplantation in Patients with Wiskott-Aldrich Syndrome. Biol Blood Marrow Transplant. 2018 Jul;24(7):1432-1440. doi: 10.1016/j.bbmt.2018.03.006. Epub 2018 Mar 14. |
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| Plerixafor for Conditioning before HSCT. | Biological | Directed inhibition of CXC chemokine receptor type 4 (CXCR4) for opening enough BM niches for adequate donor HSC engraftment. |
|
| 12 months |
| Transplant related mortality (TRM) | The TRM probability compared with historical control. | 24 months |
| Severe thrombocytopenia (ST) | The ST probability after HSCT compared with historical control | 24 months |
| Autoimmune complications (AC) | The AC probability after HSCT compared with historical control | 24 months |
| Acute Graft Versus Host Diseases (aGVHD) | Cumulative Incidence and severity of aGVHD | 12 months |
| Chronic Graft Versus Host Diseases (cGVHD) | Cumulative Incidence and severity of cGVHD | 24 months |
| Plerixafor related complications (PRC) | PRC: severity, features, incidence | 2 week |
| Principal Investigator |
| ID | Term |
|---|---|
| D014923 | Wiskott-Aldrich Syndrome |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008231 | Lymphopenia |
| D007970 | Leukopenia |
| D000095542 | Cytopenia |
| D006474 | Hemorrhagic Disorders |
| D007960 | Leukocyte Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
| D000081207 | Primary Immunodeficiency Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D016179 | Granulocyte Colony-Stimulating Factor |
| C088327 | plerixafor |
| ID | Term |
|---|---|
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
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