Allogeneic Transplantation For Severe Osteopetrosis
This trial is active, not recruiting.
|Treatments||umbilical cord blood transplantation, campath-1h, total lymphoid irradiation, cyclophosphamide, busulfan, fludarabine monophosphate, marrow graft transplantation|
|Phase||phase 2/phase 3|
|Sponsor||Masonic Cancer Center, University of Minnesota|
|Start date||August 2008|
|End date||October 2015|
|Trial size||23 participants|
|Trial identifier||NCT00775931, 0808M42261, MT2008-20|
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.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Estimate the rate of donor engraftment for patients treated by hematopoietic stem cell transplantation
time frame: Day 100
Estimate Peri-transplant mortality (deaths)
time frame: day 100
Transplant related toxicity
time frame: Day 100 post transplant
Graft-versus-host disease (incidence and severity)
time frame: after transplantation
Tolerance of Campath-1H administration
time frame: During study
Clinical Disease Monitoring
time frame: post transplant
Male or female participants up to 45 years old.
- Patients eligible for transplantation under this protocol will be < or = 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.
- Patients >45 years of age
- Evidence of hepatic failure
- Pulmonary dysfunction sufficient to significantly 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
|Official title||Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis|
|Principal investigator||Paul Orchard, MD|
|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.|
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