Combination of Ibuprofen, G-CSF and Plerixafor as Stem Cells Mobilization Regimen in Patients Affected by X-CGD

Phase 2

Recruiting

• Conditions: Chronic Granulomatous Disease X-linked (X-CGD)
• Interventions: Drug: Ibuprofen; Drug: Myelostim; Drug: Mozobil

• Registration Number: NCT03055247
• Lead Sponsor: IRCCS San Raffaele

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.

Study Timeline

• Study Start: 2015-11-06
• Study First Submitted: 2016-07-21
• Study First Submitted QC: 2017-02-13
• Study First Posted: 2017-02-16
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-27
• Last Update Posted: 2022-10-31
• Primary Completion: 2023-07-13
• Study Completion: 2023-07-18

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 3

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
• Active alcohol or substance abuse within 6 months of the study.
• Contraindications to IBU, G-CSF, Plerixafor or Pantoprazole administration

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
XCGD mobilization	Myelostim	Treatment with combination of Ibuprofen, Myelostim and Mozobil
XCGD mobilization	Mozobil	Treatment with combination of Ibuprofen, Myelostim and Mozobil
XCGD mobilization	Ibuprofen	Treatment with combination of Ibuprofen, Myelostim and Mozobil

Primary Outcome Measures

Name	Time	Method
Percentage of patients experiencing adverse events	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	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 Outcome Measures

Name	Time	Method
DHR (dihydrorhodamine) test in myeloid progeny	Through study completion, an average of 1 year	Correction of the functional defects in the differentiated myeloid progeny
Change in number of CD34+ cells in PB before and after administration of Ibuprofen	Day 6 and day 7	Cytofluorimetric analysis to determine the number of CD34+ cells present in PB on day 6 and 7 compared to before the administration of Ibuprofen
Functional characterization of mobilized CD34+ cells.	Through study completion, an average of 1 year	Repopulating activity of mobilized CD34+ cells in immunodeficient mice.
Transduction efficiency	Through study completion, an average of 1 year	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.

Trial Locations

Locations (2)

Ospedale Pediatrico Bambino Gesù; 🇮🇹 Rome, Lazio, Italy

Ospedale San Raffaele; 🇮🇹 Milan, Lombardia, Italy