Evaluating the Safety and Effectiveness of Mozobil Mobilization in Adults With Beta-Thalassemia Major
Condition: Beta-Thalassemia
MeSH terms: Thalassemia; beta-Thalassemia
Study type: Interventional

Summary: 
      Thalassemia is considered the most common genetic disorder worldwide, occurring with high
      frequency in Mediterranean areas, the Middle East, Southeast Asia, and the Pacific Islands.
      Currently, the only cure for thalassemia is bone marrow transplantation from a related,
      compatible donor. Gene transfer, achieved by transplantation of the patient's own blood stem
      cells that have been genetically-modified with the corrected gene, could potentially cure
      thalassemia.

      The first step in developing gene transfer for treatment of thalassemia is to develop a safe
      and effective method to obtain blood stem cells from thalassemia patients. Eventually, high
      numbers of genetically modified cells will need to be infused into the patient for clinical
      gene transfer to be effective. The blood stem cells are obtained by giving a "mobilization"
      agent to the patients. This causes the stem cells to leave the bone marrow and go into the
      blood. The purpose of this study is to test the safety and effectiveness of the new
      mobilization agent, Mozobil, in causing mobilization of blood stem cells for patients with
      beta-thalassemia major.
    

Detailed description: 
      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.
    

Intervention name(s): Mozobil; Mozobil; Mozobil
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Previously mobilized splenectomized patients who failed to yield sufficient numbers of cells with Mozobil alone will receive low doses G-CSF subcutaneously (starting at 2.5µg/kg/day and adjusted to the degree of leukocytosis), and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses. Previously non-splenectomized patients who failed to yield sufficient numbers of cells with Mozobil alone will receive G-CSF at 10µg/kg/day subcutaneously for 4-7 days, and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses.; Previously mobilized splenectomized patients who failed to yield sufficient numbers of cells with G-CSF in the previous study will receive low doses G-CSF subcutaneously (starting at 2.5µg/kg/day and adjusted to the degree of leukocytosis), and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses. Previously non-splenectomized patients who failed to yield sufficient numbers of cells with G-CSF in the previous study will receive G-CSF at 10µg/kg/day subcutaneously for 4-7 days, and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses.; Up to sixteen patients (splenectomized and non-splenectomized) who were not previously mobilized will receive Mozobil at 240µg/kg for one to three days, followed by one to three leukaphereses.
Other intervention name(s): Plerixafor; AMD 3100; Plerixafor; AMD3100; Plerixafor; AMD3100
Intervention MeSH terms: Plerixafor
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Beta Thalassemia Major; Hematopoietic Stem Cell Mobilization; Gene Transfer Techniques