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

October 27, 2022 updated by: Ciceri Fabio, IRCCS San Raffaele

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

3

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
    • Lazio
      • Rome, Lazio, Italy, 00165
        • Recruiting
        • Ospedale Pediatrico Bambino Gesù
        • Contact:
          • Franco Locatelli, MD, PhD
        • Sub-Investigator:
          • Andrea Finocchi, MD
    • Lombardia
      • Milan, Lombardia, Italy, 20132
        • Recruiting
        • Ospedale San Raffaele
        • Contact:
          • Fabio Ciceri, MD, PhD
        • Sub-Investigator:
          • Alessandro Aiuti, MD, PhD
        • Sub-Investigator:
          • Bernhard Gentner, MD, PhD
        • Sub-Investigator:
          • Maddalena Migliavacca, MD
        • Sub-Investigator:
          • Laura Bellio, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XCGD mobilization
Treatment with combination of Ibuprofen, Myelostim and Mozobil
Drug: Ibuprofen
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.
Drug: Myelostim
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.
Drug: Mozobil
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
up to 30 days after the last LP
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)
Day 21-24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in number of CD34+ cells in PB before and after administration of Ibuprofen
Time Frame: 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
Day 6 and day 7
Transduction efficiency
Time Frame: 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.
Through study completion, an average of 1 year
DHR (dihydrorhodamine) test in myeloid progeny
Time Frame: Through study completion, an average of 1 year
Correction of the functional defects in the differentiated myeloid progeny
Through study completion, an average of 1 year
Functional characterization of mobilized CD34+ cells.
Time Frame: Through study completion, an average of 1 year
Phenotype analysis (FACS).
Through study completion, an average of 1 year
Functional characterization of mobilized CD34+ cells.
Time Frame: Through study completion, an average of 1 year
Clonogenic activity (CFU-C) before and after transduction.
Through study completion, an average of 1 year
Functional characterization of mobilized CD34+ cells.
Time Frame: Through study completion, an average of 1 year
Repopulating activity of mobilized CD34+ cells in immunodeficient mice.
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS San Raffaele

Collaborators

Fondazione Telethon

Investigators

  • Principal Investigator: Fabio Ciceri, MD, PhD, Ospedale San Raffaele
  • Principal Investigator: Franco Locatelli, MD, PhD, Ospedale Pediatrico Bambino Gesù

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 6, 2015

Primary Completion (Anticipated)

July 13, 2023

Study Completion (Anticipated)

July 18, 2023

Study Registration Dates

First Submitted

July 21, 2016

First Submitted That Met QC Criteria

February 13, 2017

First Posted (Actual)

February 16, 2017

Study Record Updates

Last Update Posted (Actual)

October 31, 2022

Last Update Submitted That Met QC Criteria

October 27, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2015-002356-27

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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