Beta-thalassaemia major MedDRA version: 12.0 Level: LLT Classification code 10004505 Term: Beta thalassaemia MedDRA version: 12.0 Level: LLT Classification code 10004514 Term: Beta-thalassaemia MedDRA version: 12.0 Level: LLT Classification code 10043391 Term: Thalassaemia beta
Conditions
Interventions
Trade Name: Mozobil
Pharmaceutical Form: Solution for injection
INN or Proposed INN: 1, 1’ [1,4-phenylenebis (methylene)]-bis-1,4,8,11-tetraazacyclotetradecane
CAS Number: 110078-46-1
Other descripti
Sponsors
University of Washington
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) ?eta- thalassemia major b) Age >182.8 (SI/SD) or 9msec by T2*MRI h) Hepatitis B or C virus load negative by PCR i) Left ventricular ejection fraction (LVEF) >45% by echocardiogram j) Adequate respiratory function with DLCO >50% k) Negative pregnancy test, if female l) Ability to give informed consent and willingness to meet all the expected requirements of the protocol for the duration of the study 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 F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a) History of thrombosis or known thrombophilia b) Symptomatic viral, bacterial or fungal infection within 6 weeks prior eligibility evaluation c) Pregnancy or lactation d) HIV positivity e) History of malignancy, other than local skin cancer f) Other systematic disease non thalassemia-associated g) Splenectomized patients with platelet count >900,000 (only for the splenectomized patients who will receive low dose G-CSF+ Mozobil) h) Additional risk factors for thrombosis, including Factor V Leiden; antiphospholipid antibodies and less than 50% of the lowest normal value for the following procoagulants: antithrombin 3, protein C, or protein S.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: i)To determine the safety of peripheral blood stem cell (PBSC) mobilization with Mozobil alone or with G-CSF +Mozobil in adults with b thalassemia major ii) To collect with Mozobil or Mozobil+G-CSF a total of at least 6X106CD34+ cells/kg for subsequent clinical scale transduction with a beta-globin lentiviral vector, in a clinical beta-globin gene transfer trial.;Secondary Objective: i)To determine the clonogenic capacity of cells mobilized by Mozobil alone- or by G-CSF + Mozobil, ii) To determine the cells’ ability to be transduced with a recombinant lentivirus vector for b-globin iii) To determine the transduced cells’ potential to engraft in a xenograft model. ;Primary end point(s): - the safety of Mozobil or Mozobil+G-CSF mobilization in splenectomized and non-splenectomized patients with b thalassemia major - the proportion of patients who will yield greater than or equal to 6X106 CD34+cells/kg by Mozobil alone - the proportion of patients who will yield cumulatively greater than or equal to 6X106 CD34+cells/kg by the combination of Mozobil+G-CSF and who had previously failed to reach the cell dose target either with G-CSF alone or Mozobil-alone - the number of apheresis days required to reach more than or equal to 6X106 CD34+cells/kg by Mozobil alone - the number of apheresis days required to cumulatively reach more than or equal to 6X106 CD34+cells/kg by the combination of Mozobil+G-CSF in patients who had previously failed to reach this cell dose target either by G-CSF or Mozobil. Importantly, in patients previously mobilized with G-CSF alone (Thal-001 study) or with Mozobil alone (Thal-002 study) the comparison of paired samples from each patient will eliminate inter-patient variability in the analysis, as each patient will serve as his or her own control. This will allow conclusions to be drawn on the relative efficacy of the two mobilization schemes that would otherwise be difficult to draw from this number of patients. | — |
Countries
Greece
Outcome results
None listed