We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination 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. The purpose of this research is to find 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.
This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 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, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Stem Cell (unrelated or matched related donor grafts (both peripheral blood and marrow) infusion on Day 0 and 42; Umbilical Cord Blood on Day 0 and 42
* 12 Campath-1H 0.3 mg/kg intravenously (IV) over 2 hours * 11 Campath-1H 0.3 mg/kg intravenously over 2 hours * 10 Campath-1H 0.3 mg/kg intravenously over 2 hours * 9 Busulfan \<12 kg: 2.2 mg/kg/dose IV every 12 hours \>12 kg: 1.6 mg/kg/dose IV every 12 hours * 8 Busulfan \<12 kg: 2.2 mg/kg/dose IV every 12 hours \>12 kg: 1.6 mg/kg/dose IV every 12 hours * 7 "Rest" * 6 Clofarabine 40 mg/m2 intravenously over 2 hours * 5 Clofarabine 40 mg/m2 intravenously over 2 hours * 4 Clofarabine 40 mg/m2 intravenously over 2 hours * 3 Clofarabine 40 mg/m2 intravenously over 2 hours * 2 Clofarabine 40 mg/m2 intravenously over 2 hours
Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).
University of MInnesota, Fairview
Minneapolis, Minnesota, United States
Number of Patients Achieving Donor Cell Engraftment
Number of patients with persistent presence of donor-derived cells at Day 100
Time frame: Day 100
Number of Patients With Transplant Related Death
Number of participants died during study by Day 100 and reason for death was related to transplant.
Time frame: Day 100
Number of Patients With Transplant Related Toxicity
Number of patients experiencing adverse effects due to transplant categorized by body system using Common Terminology Criteria for Adverse Events coding from the National Cancer Institute, Version 3.0.
Time frame: Day 100
Differential Imaging and Biologic Evaluations
These outcome measures were not assessed due to early study termination.
Time frame: Day 100, 6 months, 1, 2 and 5 years
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