This is a phase II exploratory study conducted to evaluate the safety and efficacy of the combination of Ibuprofen, G-CSF and Plerixafor as stem cell mobilization regimen in patients affected by X-CGD.
We designed a mobilization trial with the aim of collecting a sufficient number of HSPC in X-CGD patients; it is well known that this procedure is challenging for these patients, potentially due to functional defects induced by their chronic inflammatory state. The combination of G-CSF and Plerixafor is considered state of the art for HSPC harvest in gene therapy trials; we considered to add a non-steroidal inflammatory drug to increase HSPC mobilization and reduce inflammation that could have a role in altering HSPC content. If this trial confirms the synergistic effect of the three drugs under investigation, such a regimen will be considered for a HSPC mobilization in future gene therapy trial for X-CGD patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
3
Ibuprofen: 3 mg/kg tid (total daily dose: 9 mg/kg); administered orally from day 1 to day 5 and then from day 14 to the day before the last LP.
Myelostim (G-CSF): 5 µg/kg bid (total daily dose 10 µg/kg); administered subcutaneously from day 19 to the day of the last LP.
Mozobil (Plerixafor): 0,24 mg/kg daily. When CD34+ are ≥ 10 /μL Plerixafor will be administered subcutaneously from the next day (or from day 24 if CD34+ are \< 10 /μL) to the day of the last LP.
Ospedale Pediatrico Bambino Gesù
Rome, Lazio, Italy
RECRUITINGOspedale San Raffaele
Milan, Lombardy, Italy
RECRUITINGPercentage of patients experiencing adverse events
Percentage of patients experiencing adverse events, as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAe v3.0, 2006) (all grades).
Time frame: up to 30 days after the last LP
Number of CD34+ collected per body weight after the last LP
Cytofluorimetric analysis for CD34 on PB and on collected PBSC to calculate the number of CD34+ cells collected per kg body weight. The analysis will be performed at the end of the LP(s) (Day 21-24)
Time frame: Day 21-24
Change in number of CD34+ cells in PB before and after administration of Ibuprofen
Cytofluorimetric analysis to determine the number of CD34+ cells present in PB on day 6 and 7 compared to before the administration of Ibuprofen
Time frame: Day 6 and day 7
Transduction efficiency
Efficient transduction of mobilized HSPC with a lentiviral vector encoding for a corrective cDNA of the human gp91phox gene. Frequency and Vector Copy Number tested by PCR.
Time frame: Through study completion, an average of 1 year
DHR (dihydrorhodamine) test in myeloid progeny
Correction of the functional defects in the differentiated myeloid progeny
Time frame: Through study completion, an average of 1 year
Functional characterization of mobilized CD34+ cells.
Phenotype analysis (FACS).
Time frame: Through study completion, an average of 1 year
Functional characterization of mobilized CD34+ cells.
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Clonogenic activity (CFU-C) before and after transduction.
Time frame: Through study completion, an average of 1 year
Functional characterization of mobilized CD34+ cells.
Repopulating activity of mobilized CD34+ cells in immunodeficient mice.
Time frame: Through study completion, an average of 1 year