Clinical trial NCT00775931: Allogeneic Transplantation For Severe Osteopetrosis
Official title: Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Severe Osteopetrosis
Keywords: osteopetrosis
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-10-20
Enrollment: 7
Sex: ALL
Minimum age (years): 1
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* 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.

  1. Bones that are uniformly markedly dense based on skeletal survey
  2. No history that would suggest autosomal dominant inheritance
  3. 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 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

Primary outcomes:
measure: Number of Patients Who Achieved Donor Cell Engraftment
timeFrame: Day 100
Secondary outcomes:
measure: Transplant Related Mortality at 100 Days
timeFrame: day 100
measure: Transplant Related Toxicity
timeFrame: Day 100 post transplant
measure: Incidence of Grade II - IV Acute Graft-versus-host Disease
timeFrame: by Day 100 after transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of MInnesota, Fairview
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Paul Orchard, MD
role: PRINCIPAL_INVESTIGATOR
References: