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

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ClinicalTrials.gov Identifier: NCT03055247
Recruitment Status : Recruiting
First Posted : February 16, 2017
Last Update Posted : May 30, 2017
Sponsor:
Collaborator:
Fondazione Telethon
Information provided by (Responsible Party):
Ciceri Fabio, 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.

Condition or disease Intervention/treatment Phase
Chronic Granulomatous Disease X-linked (X-CGD) Drug: Ibuprofen Drug: Myelostim Drug: Mozobil Phase 2

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  (Clinical Trial)
Estimated Enrollment : 3 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: 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
Study Start Date : November 2015
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : August 2018


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.




Primary Outcome Measures :
  1. 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).

  2. 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 Outcome Measures :
  1. 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

  2. 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.

  3. 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

  4. Functional characterization of mobilized CD34+ cells. [ Time Frame: Through study completion, an average of 1 year ]
    Phenotype analysis (FACS).

  5. Functional characterization of mobilized CD34+ cells. [ Time Frame: Through study completion, an average of 1 year ]
    Clonogenic activity (CFU-C) before and after transduction.

  6. 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.



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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  • Active alcohol or substance abuse within 6 months of the study.
  • Contraindications to IBU, G-CSF, Plerixafor or Pantoprazole administration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03055247


Contacts
Contact: Fabio Ciceri, MD, PhD 39 02.2643.3903 ciceri.fabio@hsr.it
Contact: Alessandro Aiuti, MD, PhD +390226434875 aiuti.alessandro@hsr.it

Locations
Italy
Ospedale Pediatrico Bambino Gesù Recruiting
Rome, Lazio, Italy, 00165
Contact: Franco Locatelli, MD, PhD         
Sub-Investigator: Andrea Finocchi, MD         
Ospedale San Raffaele Recruiting
Milan, Lombardia, Italy, 20132
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         
Sponsors and Collaborators
IRCCS San Raffaele
Fondazione Telethon
Investigators
Principal Investigator: Fabio Ciceri, MD, PhD Ospedale San Raffaele
Principal Investigator: Franco Locatelli, MD, PhD Ospedale Pediatrico Bambino Gesù

Publications of Results:

Responsible Party: Ciceri Fabio, Director Hematology and BMT Unit, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT03055247     History of Changes
Other Study ID Numbers: 2015-002356-27
First Posted: February 16, 2017    Key Record Dates
Last Update Posted: May 30, 2017
Last Verified: May 2017

Keywords provided by Ciceri Fabio, IRCCS San Raffaele:
Chronic granulomatous disease X-linked
Ibuprofen
Mobilization regimen
Gene Therapy

Additional relevant MeSH terms:
Granulomatous Disease, Chronic
Granuloma
Lymphoproliferative Disorders
Lymphatic Diseases
Pathologic Processes
Phagocyte Bactericidal Dysfunction
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Ibuprofen
JM 3100
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents