Evaluation of safety and efficacy of the combination of Ibuprofen (IBU), G-CSF and Plerixafor as a stem cell mobilization regimen in patients affected by XCGD

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2015-002356-27-IT
• Date of registration: 29/07/2015
• Prospective Registration: Yes
• Primary sponsor: Ospedale San Raffaele
• Public title: Evaluation of safety and efficacy of the combination of Ibuprofen (IBU), G-CSF and Plerixafor as a stem cell mobilization regimen in patients affected by XCGD
• Scientific 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 a stem cell mobilization regimen in patients affected by X-CGD.
• Date of first enrolment: 16/10/2015
• Target sample size: 3
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002356-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Italy

Contacts

• Name: TIGET Clinical Trial Office (TCTO)
• Affiliation: Ospedale San Raffaele

• Name: TIGET Clinical Trial Office (TCTO)
• Affiliation: Ospedale San Raffaele

Key inclusion & exclusion 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Previous Bone Marrow Transplantation or previous Gene Therapy.
•Use of other investigational agents within 4 weeks prior to study en-rolment (within 6 weeks if use of long-acting agents).
•Ongoing IFN-? treatment (within 4 weeks).
•Symptomatic inflammatory bowel disease.
•Symptomatic viral, bacterial, or fungal infection within 6 weeks of eli-gibility evaluation or active infection (including fever of unknown origin)
•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


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

X-linked chronic granulomatous disease
MedDRA version: 18.0 Level: PT Classification code 10008906 Term: Chronic granulomatous disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Ibuprofen
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IBUPROFEN
CAS Number: 15687-27-1
Current Sponsor code: NA
Other descriptive name: NA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: MYELOSTIM 34 milions UI/ml, powder and solvent for solution for injection or infusion
Product Name: MYELOSTIM 34 milions UI/ml - powder and solvent for solution for injection/infusion
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
INN or Proposed INN: LENOGRASTIM
CAS Number: 135968-09-1
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 34-

Trade Name: Mozobil 20mg/mL vial (injectable solution for subcutaneous use)
Product Name: Mozobil 20mg/mL vial (injectable solution, subcutaneous use)
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Plerixafor
CAS Number: 110078-46-1
Other descriptive name: Plerixafor
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Pantoprazolo 20 mg gastro-resistant tablets
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: Pantoprazole
CAS Number: 102625-70-7
Other descriptive name: PANTOPRAZOLE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) From Day 0 to 30 days after the last LP
2) from the first to the last LP

Primary end point(s): 1) Safety
Incidence and severity of adverse events following IBU, G-CSF and Plerixafor administration (any grade) occurring between day 0 and 30 days after the last LP.
2) Efficacy - Harvest of >= 8X10^6 CD34+/Kg in one or more collections

Secondary Objective: 1. To explore the effect of Ibuprofen in mobilizing CD34+ cells in the PB.
2. To explore the in vitro efficacy of a lentiviral vector encoding for a corrective cDNA of the human gp91phox gene in transducing CD34+ cells obtained by the XCGD-MOBI protocol and correcting the func-tional defects in the differentiated myeloid progeny.
3. To functionally characterize the properties of IBU, G-CSF and Plerixafor mobilized CD34+ cells from X-CGD patients

Main Objective: 1. To explore the safety of IBU, G-CSF and Plerixafor when administered as a stem cell mobilization regimen in patients affected by X-CGD.
2. To explore the effect of IBU, G-CSF and Plerixafor in mobilizing CD34+ cells thus allowing the collection of a number of HSPC deemed sufficient for ex vivo gene therapy in patients affected by X-CGD.

Secondary Outcome(s)

Secondary end point(s): 1.Increase in PB CD34+ cell count after administration of Ibuprofen.
2.Efficient transduction of mobilized HSPC and oxidase activity restoration in their myeloid progeny following gene transfer with a lentiviral vector encoding for human gp91phox.
3.Maintenance of repopulating activity of transduced HSPC in immunodeficient mice

Timepoint(s) of evaluation of this end point: NA

Secondary ID(s)

XCGD_MOBI1

Source(s) of Monetary Support

Fondazione Telethon