Treatment of Chronic Granulomatous Disease With Allogeneic Stem Cell Transplantation Versus Standard of Care

Chronic Granulomatous Disease Clinical Trial

Official title: Treatment of Chronic Granulomatous Disease With Allogeneic Stem Cell Transplantation Versus Standard of Care

Status Completed

Clinical Trial Summary

This study will compare the health and well being of children treated with a modified stem cell transplantation procedure for chronic granulomatous disease (CGD) with that of children receiving standard of care treatment. CGD is an inherited disorder of neutrophils-a type of infection-fighting white blood cell-that leaves patients vulnerable to life-threatening infections. Standard treatment with antibiotics, and sometimes surgery, is not always successful, and patients with persisting infections have a poor long-term prognosis.

Transplantation of donated stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) can improve immune function in patients with CGD and possibly cure the disease. However, this procedure carries a significant risk of death, because it requires complete suppression of the immune system with high-dose chemotherapy. In addition, lymphocytes-another type of infection-fighting white blood cell-from the donor may cause what is called graft versus host disease (GvHD), in which the donor cells 'see' patient's cells as foreign and mount an immune response to reject them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression. Also, the donor's lymphocytes will be removed from the rest of the stem cells to be transplanted, reducing the risk of GvHD.

Patients with CGD between 2 and 17 years of age who 1) are currently free of active infection, and 2) have a history of at least one life-threatening infection or a family member with CGD and a history of at least one life-threatening infection, and 3) a family member that is a suitable donor may be eligible for this study. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, x-rays or 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 (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. Then, the stem cells will be collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the required cells are separated out and removed. Then, the rest of the blood is returned through a needle in the other arm.

Several days before the transplant procedure, patients will start a 'conditioning regimen' of chemotherapy with cyclophosphamide, fludarabine and Campath 1H. When the conditioning therapy is completed, the donor's 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 to the NIH clinic 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 clinic visits will be scheduled 1 to 3 times a year for at least 5 years.

Clinical Trial Description

Chronic Granulomatous Disease (CGD) is one of several inherited disorders 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 with CGD. The primary objective of this study is to investigate efficacy of a novel approach to allogeneic stem cell transplantation, which is designed to promote partial or complete donor stem cell engraftment (hematopoietic chimerism) with reduced transplant related 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. The graft will be enriched for hematopoietic stem cells in an attempt to decrease the risk of graft versus 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. Patients treated with this approach will be compared to patients who are considered transplant-eligible but lack an HLA identical family member. These patients will be treated using the current standard of care. The primary end points of this study are to demonstrate reduced incidence of CGD-like infections in the transplanted patients compared to the controls (efficacy) with acceptable incidence of acute and chronic graft versus host disease and transplant related mortality (safety). Long term follow up data from transplanted patients and concurrent controls will be analyzed to confirm the association between establishment of hematopoietic chimerism and clinical benefit. ;

Study Design

Endpoint Classification: Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Granulomatous Disease
• Granuloma
• Granulomatous Disease, Chronic

• NCT number: NCT00023192
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 3
• Start date: August 2001
• Completion date: June 2004