Clinical trial NCT03019809: A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients
Official title: A Trial of Plerixafor With G-CSF as Additional Agents in Conditioning Regimen for Prevention of Graft Failure After Transplantation With TCR Alpha/Beta Grafts Depletion in Patients With Wiskott-Aldrich Syndrome.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Wiskott-Aldrich Syndrome
Hematopoietic Stem Cell Transplantation
Graft Failure
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
First posted: 2017-01-13
Enrollment: 30
Sex: ALL
Minimum age (years): 1
Maximum age (years): 19
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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Event free survival (EFS)
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 24 months
measure: Percentage of patients with full/mixed donor chimerism
timeFrame: 12 months
measure: Transplant related mortality (TRM)
timeFrame: 24 months
measure: Severe thrombocytopenia (ST)
timeFrame: 24 months
measure: Autoimmune complications (AC)
timeFrame: 24 months
measure: Acute Graft Versus Host Diseases (aGVHD)
timeFrame: 12 months
measure: Chronic Graft Versus Host Diseases (cGVHD)
timeFrame: 24 months
measure: Plerixafor related complications (PRC)
timeFrame: 2 week
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
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.