Reduced Intensity AlloTransplant For Osteopetrosis
Condition: Osteopetrosis
MeSH terms: Osteopetrosis
Intervention: Stem Cell or Umbilical Cord Blood Transplantation; Campath, Busulfan, Clofarabine; Total Lymphoid Irradiation
Intervention description: 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).
Intervention MeSH terms: Busulfan; Alemtuzumab; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Maximum age: 45 Years
Healthy volunteers: No
Keywords: osteopetrosis

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients eligible for transplantation under this protocol will be <45 years of age,
             and will be diagnosed with severe osteopetrosis. This will be defined as having the
             following manifestations of the disease.

          -  Bones that are uniformly markedly dense based on skeletal survey

          -  No history that would suggest autosomal dominant inheritance

          -  Evidence of hematologic changes that are attributed to the underlying disease,
             including the need for ongoing transfusions, OR

          -  the presence of progressive anemia or thrombocytopenia, OR a white blood cell
             differential with a predominance of immature forms and evidence of extramedullary
             hematopoiesis, OR

          -  persistence of serious infectious complications that are thought to be due to the
             abnormal architecture of the bone that are resistant to surgical and medical
             interventions.

        Exclusion Criteria:

          -  Patients >45 years of age

          -  Evidence of hepatic failure

          -  pulmonary dysfunction sufficient to substantially increase the risk of transplant

          -  Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.

          -  Cardiac compromise sufficient to substantially increase the risk of transplantation

          -  Severe, stable neurologic impairment.

          -  Human immunodeficiency virus (HIV) positivity.

          -  Pregnant or lactating females