A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients

Phase 2

Conditions: Graft Failure
Wiskott-Aldrich Syndrome
Hematopoietic Stem Cell Transplantation

Interventions: Biological: G-CSF for Conditioning before HSCT.
Biological: Plerixafor for Conditioning before HSCT.

Lead Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Plerixafor/G-CSF for HSCT conditioning	G-CSF for Conditioning before HSCT.	Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients.
Plerixafor/G-CSF for HSCT conditioning	Plerixafor for Conditioning before HSCT.	Myeloablative conditioning regimen with Plerixafor and G-CSF as addition agents before stem cell transplantation in WAS patients.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Chronic Graft Versus Host Diseases (cGVHD)	24 months	Cumulative Incidence and severity of cGVHD
Overall survival (OS)	24 months	The OS probability compared with historical control.
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
Autoimmune complications (AC)	24 months	The AC probability after HSCT compared with historical control
Acute Graft Versus Host Diseases (aGVHD)	12 months	Cumulative Incidence and severity of aGVHD
Plerixafor related complications (PRC)	2 week	PRC: severity, features, incidence

Locations (1): Dmitry Rogachev Federal Research and Clinical Centre of Paediatric Haematology, Oncology and Immunology
🇷🇺
Moscow, Russian Federation