Clinical Trial: Mobilization and Collection of Peripheral Blood Stem Cells in Patients With Fanconi Anemia Using G-CSF and AMD3100
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: AMD3100 in Combination With G-CSF to Mobilize Peripheral Blood Stem Cells in Patients With Fanconi Anemia(FA): A Phase I/II Study
Brief Summary:
The purpose of this research study is to determine whether an experimental drug called AMD3100 used in combination with another medication called G-CSF is safe and can help to increase the amount of blood stem cells (called CD34+ stem cells) found in the peripheral blood of patients with Fanconi anemia. While AMD3100 has been used successfully in adult volunteers and cancer patients, it has not been used in children or patients with Fanconi anemia and in only a few children with cancer.
Fanconi anemia is a rare genetic disease. Most Fanconi anemia patients eventually develop bone marrow failure, a condition in which the bone marrow no longer produces red blood cells (to carry oxygen), white blood cells (to fight infection), and platelets (to help blood clot). The only successful treatment for patients with Fanconi anemia with bone marrow failure is bone marrow transplantation. However, this treatment has many risks and is not available to all patients with Fanconi anemia.
CD34+ cells include stem cells found in the bone marrow or peripheral blood which are capable of making the red blood cells, white blood cells, and platelets. CD34+ stem cells can be collected from bone marrow or peripheral blood and purified using an experimental device called the CliniMACS. However, most Fanconi anemia patients do not have enough CD34+ stem cells in their bone marrow or peripheral blood to be collected using standard methods that work well in children and adults who don't have Fanconi anemia.
Detailed Summary:
Fanconi anemia is a rare autosomal recessive syndrome comprised of progressive bone marrow failure, congenital anomalies and a predisposition to malignancy. The heterozygote rate in the United States may be as high as 1 in 300. The mean age for the onset of aplastic anemia is approximately eight years. Although improved supportive care has prolonged the survival of these patients from only a few years from the diagnosis of bone marrow failure, the mean age of death is still approximately 24 years of age. Most patients die from complications of bone marrow failure including bleeding, or infection, or from malignancy or complications of stem cell transplantation. In a recent 20 year review of patients in the Fanconi anemia registry, the actual risk of developing leukemia or other cancers was approximately 30%.
The diagnosis of Fanconi anemia initially rested upon finding the combination of bone marrow failure with congenital anomalies. These anomalies include cafe au lait spots and/or hypo pigmentation of the skin, short stature, upper limb malformations (often involving the thumb or radius), renal and gastrointestinal abnormalities, microcephaly, and characteristic facies with a broad nasal base, epicanthal folds, narrow set and small eyes and micrognathia. The bone marrow failure is characterized by slow progression to severe bone marrow aplasia and pancytopenia, stress erythropoiesis with fetal features including macrocytosis, elevated hemoglobin F, and i antigen expression. Attempts to culture bone marrow progenitors in vitro from patients with Fanconi anemia demonstrates decreased numbers of myeloid and erythroid colonies (CFU) consistent with clinical bone marrow failure.
Fanconi anemia cells appear to have a defect in DNA repair that leads to increased spontaneous chromosomal breakage. This feature increases the susce
Sponsor: Children's Hospital Medical Center, Cincinnati
Current Primary Outcome: Measure safety and efficacy of AMD3100 used in combination with standard dose G-CSF in Fanconi anemia patients to mobilize sufficient number of peripheral blood CD34+ cells for peripheral blood apheresis. [ Time Frame: 2 years ]
Original Primary Outcome: Measure safety and efficacy of AMD3100 used in combination with standard dose G-CSF in Fanconi anemia patients to mobilize sufficient number of peripheral blood CD34+ cells for peripheral blood apheresis.
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Children's Hospital Medical Center, Cincinnati
Dates:
Date Received: May 23, 2007
Date Started: May 2007
Date Completion:
Last Updated: February 15, 2012
Last Verified: February 2012
