A Multicentric, Exploratory, Non-randomised, Non-controlled, Prospective, Open-label Phase II Study Evaluating Safety and Efficacy of IBU, G-CSF and Plerixafor as Stem Cell Mobilization Regimen in Patients Affected by X-CGD
Overview
- Phase
- Phase 2
- Intervention
- Mozobil
- Conditions
- Chronic Granulomatous Disease X-linked (X-CGD)
- Sponsor
- IRCCS San Raffaele
- Enrollment
- 3
- Locations
- 2
- Primary Endpoint
- Percentage of patients experiencing adverse events
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Ciceri Fabio
Director Hematology and BMT Unit
IRCCS San Raffaele
Eligibility Criteria
Inclusion Criteria
- •Genetic diagnosis of X-CGD
- •18-45 years of age
- •Karnofsky Index \> 80 %
- •Adequate cardiac, renal, hepatic and pulmonary function.
- •Negative thrombophilic screen and negative history for previous thrombotic events
- •Written informed consent
Exclusion Criteria
- •Previous Bone Marrow Transplantation or previous Gene Therapy.
- •Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents).
- •Ongoing IFN-γ treatment (within 4 weeks).
- •Symptomatic inflammatory bowel disease.
- •Symptomatic viral, bacterial, or fungal infection within 6 weeks of eligibility
- •Neoplasia (except local skin cancer) or history of "familial" cancer
- •Myelodysplasia or other serious hematological disorder
- •History of uncontrolled seizures and deep venous thrombosis
- •Other systemic disease judged as incompatible with the procedure
- •Positivity for HIV and/or HCV RNA and/or HbsAg and/or HBV DNA
Arms & Interventions
XCGD mobilization
Treatment with combination of Ibuprofen, Myelostim and Mozobil
Intervention: Mozobil
XCGD mobilization
Treatment with combination of Ibuprofen, Myelostim and Mozobil
Intervention: Ibuprofen
XCGD mobilization
Treatment with combination of Ibuprofen, Myelostim and Mozobil
Intervention: Myelostim
Outcomes
Primary Outcomes
Percentage of patients experiencing adverse events
Time Frame: up to 30 days after the last LP
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).
Number of CD34+ collected per body weight after the last LP
Time Frame: Day 21-24
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)
Secondary Outcomes
- DHR (dihydrorhodamine) test in myeloid progeny(Through study completion, an average of 1 year)
- Change in number of CD34+ cells in PB before and after administration of Ibuprofen(Day 6 and day 7)
- Functional characterization of mobilized CD34+ cells.(Through study completion, an average of 1 year)
- Transduction efficiency(Through study completion, an average of 1 year)