Allogeneic Transplantation For Severe Osteopetrosis
Condition: Severe Osteopetrosis
MeSH terms: Osteopetrosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of this research is to explore what we believe may be a safer and more effective
      means of performing stem cell transplantation in patients with Osteopetrosis, using
      chemotherapy and radiation designed to bring about engraftment and lessen transplant
      mortality. Prior multi-institutional data in past studies found that approximately 30% of
      Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced
      intensity design of pre-transplant drugs to try to make transplants safer for this disease,
      as well as to provide a second infusion of stem cells in patients with matched related or
      unrelated donors.
    

Detailed description: 
      This revised transplant protocol will test the following: 1) the ability to achieve
      engraftment with the reduced intensity protocol and a second infusion of stem cells on day
      42, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on
      differential imaging and biologic evaluations prior to transplantation and at designated
      points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic
      studies will include microarray analysis, and evaluation of blood parameters and genes that
      may be important in the disease process. In older patients, studies to evaluation osteoclast
      differentiation and function will also be offered.
    

Intervention name(s): umbilical cord blood transplantation; Campath-1H; Total Lymphoid Irradiation; Cyclophosphamide; Busulfan; Fludarabine monophosphate; marrow graft transplantation
Intervention type(s): Procedure; Drug; Radiation; Drug; Drug; Drug; Procedure
Intervention description(s): Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight.; Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.; Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA).; Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only.; patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.; Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.; Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42.
Other intervention name(s): UCBT; Alemtuzumab; TLI; Cytoxan; Busulfex; Fludara; HSCT
Intervention MeSH terms: Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Alemtuzumab
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: osteopetrosis