Evaluating the Safety and Effectiveness of Mozobil Mobilization in Adults With Beta-Thalassemia Major

• Safety and effectiveness of Mozobil for mobilization of patients with beta thalassemia major [ Time Frame: Five weeks ] [ Designated as safety issue: Yes ]
  i) To determine the safety of peripheral blood stem cell (PBSC) mobilization with Mozobil alone or with Mozobil + G-CSF in adults with b-thalassemia major ii) To collect with Mozobil or Mozobil+G-CSF a total of at least 6X106CD34+ cells/kg for a subsequent clinical beta-globin gene transfer trial.
  
  

• Clonogenic capacity, transducibility, and engraftment potential (in a mouse model) of genetically modified cells [ Time Frame: Six months ] [ Designated as safety issue: Yes ]
  Secondary: i)To determine the clonogenic capacity of cells mobilized by Mozobil alone, or by Mozobil + G-CSF, ii) To determine the cells' ability to be transduced with a recombinant lentivirus vector for beta-globin, iii) To determine the transduced cells' potential to engraft in a xenograft model.
  
  

The purpose of this study is to optimize blood stem cell mobilization in adults with beta thalassemia major. We seek a method of mobilization that will be safe, with minimum side effects, and that will yield high numbers of blood stem cells. For successful gene therapy of thalassemia, high numbers of genetically modified stem cells will need to be introduced into the patient. Participants will include beta-thalassemia patients who failed to mobilize sufficiently with G-CSF (in our previous protocol) and new patients. In this study we will focus on the safety and effectiveness of mobilization with Mozobil or with Mozobil plus G-CSF. Following mobilization, blood stem cells will be recovered using leukapheresis, a procedure similar to a blood donation, in which mobilized white blood cells are collected from the blood of the patient.

During drug administration and leukapheresis, patients will be hospitalized at George Papanicolaou Hospital in Thessaloniki, Greece. Patients who failed to mobilize in the previous protocol will receive Mozobil and G-CSF and will be hospitalized for 5-8 days for the duration of drug administration and leukapheresis. They will receive G-CSF for several days; Mozobil will be added on the last few days of G-CSF. New patients will receive Mozobil only and will be hospitalized for 2-3 days for drug administration and leukapheresis. Mozobil is administered at 240µg/kg, under the skin. Participants will undergo two or three leukapheresis procedures in a row if low numbers of blood stem cells were recovered in the first (and possibly second) leukapheresis. Participants will be discharged from the hospital the day following the last leukapheresis procedure. Weekly follow-up visits will occur for the next month, either at G. Papanicolaou Hospital, or at the participant's local doctor's office. The total period of study participation is approximately 5 weeks. In the event that Mozobil alone does not cause mobilization of high levels of blood cells, patients will be invited to repeat the protocol three months later, receiving Mozobil and G-CSF.