Leukocyte-Adhesion Deficiency Syndrome Clinical Trial
Official title:
Treatment of Leukocyte Adhesion Deficiency With Allogeneic Stem Cell Transplantation
This study will investigate the safety and effectiveness of a modified stem cell transplant
procedure for treating leukocyte adhesion deficiency (LAD). LAD is an inherited blood
disorder of leukocytes (infection-fighting white blood cells) that leaves patients
vulnerable to life-threatening infections. Transplantation of donated stem cells (cells
produced by the bone marrow that mature into blood cells) can improve the immune system of
patients with LAD. However, this procedure carries a significant risk of death, particularly
in patients with active infection because it requires completely suppressing the immune
system with high-dose chemotherapy and radiation. In addition, T-cells (a type of white
blood cell) from the donor may cause what is called graft vs. host disease (GvHD), in which
the donor cells recognize the patient's cells as foreign and mount an immune response to
destroy them. To try to reduce these risks, the donor's T-cells will be removed from the
rest of the stem cells to be transplanted.
Patients with LAD who weigh at least 12 kg (26.4 LB), who do not have an active infection,
and who have a family member that is a well-matched donor may be eligible for this study.
Pregnant or breast feeding women may not participate. Candidates will have a medical
history, physical examination and blood tests, lung and heart function tests, X-rays or
computed tomography (CT) scans of the body, and dental and eye examinations. They will fill
out questionnaires that measure emotional well being, quality of life and intelligence (the
ability to learn and understand).
Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF
will be injected under the skin for several days to move stem cells from the bone marrow to
the bloodstream. The stem cells will be collected by apheresis, where blood is drawn through
a needle placed in one arm and pumped into a machine separating and removing the required
cells. The rest of the blood is then returned through a needle in the other arm.
Before the transplant, a central venous line (large plastic tube) is placed into a major
vein. This tube can stay in the body and be used during the entire treatment period to
deliver the donated stem cells, give medications, transfuse blood, if needed, and withdraw
blood samples. Several days before the transplant procedure, patients will begin a
conditioning regimen of low-dose chemotherapy with cyclophosphamide, fludarabine, and
Campath 1H. When the conditioning therapy is completed, the stem cells will be infused. To
help prevent rejection of donor cells, cyclosporine will be given by mouth or by vein
starting 1 month after the transplant procedure.
The average hospital stay for stem cell transplantation is 21 days. After discharge,
patients will return for follow-up clinic visits weekly or twice weekly for 2 to 3 months.
These visits will include a symptom check, physical examination, and blood tests. Subsequent
visits will be scheduled at 4, 6, 9, and 12 months after the transplant, or more often if
required, and then yearly
Leukocyte Adhesion Deficiency (LAD) is an inherited disorder of leukocyte function. Patients are profoundly immunocompromised and plagued early in life with recurrent and often life threatening infections. Allogeneic stem cell transplantation significantly improves immune function in patients LAD however severe toxicities are associated with conventional approaches to treatment. The primary objective of this phase II study is to investigate efficacy of a novel approach to allogeneic stem cell transplantation that is designed to promote partial or complete donor stem cell engraftment (hematopoietic chimerism) with reduced transplant morbidity and mortality. In an attempt to reduce toxicity from pre-transplant bone marrow conditioning, a highly immunosuppressive, low intensity bone marrow conditioning regimen will be used. Patients will be transplanted with peripheral blood stem cells from an HLA identical family member. T-lymphocytes will be removed from the stem cell graft in an attempt to decrease the risk of graft vs host disease. Donor T-cells will be infused at various time points following the transplant to augment donor hematopoietic chimerism and aid in immune reconstitution. The primary end points of this study are the establishment of donor hematopoietic chimerism, acute and chronic graft versus host disease, and transplant related mortality. ;
Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment