Chronic Granulomatous Disease Clinical Trial
Official title:
Low Intensity Preparative Regimen Followed by HLA-Matched, Mobilized Peripheral Blood Stem Cell Transplantation for Chronic Granulomatous Disease
This study will investigate the safety and effectiveness of a modified stem cell transplant
procedure for treating chronic granulomatous disease (CGD) in patients with active
infection. CGD is an inherited disorder of neutrophils-a type of infection-fighting white
blood cell-that leaves patients vulnerable to life-threatening infections. Transplantation
of donated stem cells (cells produced by the bone marrow that mature into the different
blood components-white cells, red cells and platelets) can cure CGD. 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, lymphocytes-another type of infection-fighting 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, patients in this study will be given low-dose chemotherapy and no
radiation, a regimen 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 the ages of age 1 and 55 years old 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. Candidates will have a medical history, physical examination and blood tests, lung
and heart function tests, X-rays of the chest and sinuses, and dental and eye examinations.
A bone marrow sample may be taken to evaluate disease status. This test, done under a local
anesthetic, uses a special needle to draw bone marrow from the hipbone.
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 increase stem cell production. Then, the
stem cells will be collected by apheresis. In this procedure the blood is drawn through a
needle placed in one arm, pumped into a machine where the desired cells are separated out
and removed, and then the rest of the blood is returned through a needle in the other arm.
A large plastic tube (central venous line) is placed into a major vein. It can stay in the
body and be used the entire treatment period to deliver the donated stem cells, give
chemotherapy or other medications, including antibiotics and blood transfusions, if needed,
and withdraw blood samples. Several days before the transplant procedure, patients will
start low-dose chemotherapy with cyclophosphamide and fludarabine, two commonly used
anti-cancer drugs. They will also be given anti-thymocyte globulin to prevent rejection of
the donated cells. When this conditioning therapy is completed, the stem cells will be
infused through the central line. Patients will be given cyclosporine by mouth or by vein
from 4 days before until 3 months after the stem cell transplant to help prevent rejection.
The average hospital stay for stem cell transplant is 30 days. After discharge, patients
will return for follow-up clinic visits weekly or twice weekly for 4 months. These visits
will include a symptom check, physical examination, and blood tests. Blood transfusions will
be given if needed. Subsequent visits will be scheduled at 4, 6, 12, 18, 24, 30 and 36
months after the transplant or more often if required, and then yearly.
Status | Completed |
Enrollment | 60 |
Est. completion date | February 2005 |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A and older |
Eligibility |
INCLUSION CRITERIA: PATIENT CRITERIA: Ages 1 to 55 years DHR proven Chronic Granulomatous Disease: Includes gp91phox, p47phox, p22phox and p67phox deficiency. Free of active infection. Patient has experienced 2 or more prior infections requiring treatment with intravenous anti-bacterial or anti-fungal therapy. HIV negative. No major organ dysfunction precluding transplantation. HLA identical sibling or parent compatible at all 6 of the HLA A, B, and DR antigens by serotyping or DNA typing techniques. Left ventricular ejection fraction: greater than 40% predicted. ECOG performance status of 0 or 1. DONOR CRITERIA: HLA identical sibling donor or parent donor. Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke, no history of severe heart disease). Female x-linked CGD carriers must have greater than 30% normal neutrophils. EXCLUSION CRITERIA: Patient or donor pregnant. Age greater than 55 years. ECOG performance status of 2 or more. Evidence of rapid deterioration due to progressive infection and/or organ damage. Left ventricular ejection fraction: greater than or equal to 35 percent predicted. Creatinine Clearance greater than or equal to 50. Serum bilirubin greater than or equal to 4 mg/dl, transaminases greater than or equal to 3x upper limit or normal. HIV negative. Donors who are positive for HBV, HCV or HTLV will be used at the discretion of the investigator. Malignant diseases liable to relapse or progress within 5 years. Donors unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of stroke, history of heart disease, thrombocytopenia.) |
Endpoint Classification: Safety Study, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | National Institute of Allergy and Infectious Diseases (NIAID) | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Giralt S, Estey E, Albitar M, van Besien K, Rondón G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Kørbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997 Jun 15;89(12):4531-6. — View Citation
Ho CM, Vowels MR, Lockwood L, Ziegler JB. Successful bone marrow transplantation in a child with X-linked chronic granulomatous disease. Bone Marrow Transplant. 1996 Jul;18(1):213-5. Review. — View Citation
Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998 Feb 1;91(3):756-63. — View Citation
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