Plerixafor/G-CSF as Additional Agents for Conditioning Before HSCT in CGD Patients

Study Overview
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Brief Summary
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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 in patients with chronic granulomatous disease

Detailed Description
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Severe primary or secondary graft dysfunction is one of major problem in patients with Chronic granulomatous disease (CGD). In this study the hypothesis is that the use of plerixafor and G-CSF as additional agents in conditioning regimen would offers advantages. The effect is based on mobilizing bone marrow stem cells into the peripheral blood and blocking CXCR4 chemokine receptors to prevent stem cell homing. Thus, some have hypothesized that plerixafor and G-CSF make free stromal space of the bone marrow available for donor stem cell engraftment. 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. 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 stem cell transplantation in patients with chronic granulomatous disease.

Official Title
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A Clinical Trial of Plerixafor With G-CSF as Additional Agents in Conditioning Regimen for Prevention of Graft Failure in Patients With Chronic Granulomatous Disease

Conditions
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Chronic Granulomatous Disease

Intervention / Treatment
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* Drug: Plerixafor
* Drug: Gcsf


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 1 months and < 25 years Patients diagnosed with CGD eligible for an allogeneic transplantation Signed written informed consent Exclusion Criteria: Lack of informed consent.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 24 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plerixafor/G-CSF<br>Plerixafor/G-CSF for HSCT conditioning Myeloablative conditioning regimen with Plerixafor as addition agent before stem cell transplantation in CGD patients | Drug: Plerixafor<br>* Plerixafor for Conditioning before HSCT.<br>Drug: Gcsf<br>* GCSF for Conditioning before HSCT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival | The EFS probability compared with historical control. We mean event as primary (non-engraftment) and secondary (rejection) graft dysfunction. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Overall survival | The OS probability compared with historical control | 1 year | 
| Proportion 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 | 30 days | 
| 3. Transplant related mortality | The TRM probability compared with historical control. | 1 year | 
| 4. Acute Graft Versus Host Diseases | Cumulative Incidence of aGVHD | 100 days | 
| 5. Incidence of Plerixafor related toxicity | severity, features, incidence | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stem cell transplantation, plerixafor, chronic granulomatous disease, graft failure, conditioning regimen