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HLA-Matched, Peripheral Blood Stem Cell Transplantation Using Low Intensity Conditioning to Treat Patients With Chronic Granulomatous Disease Who Are Actively Infected

Phase 2
Not Enrolling
Chronic Granulomatous Disease

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Trial Information

HLA-Matched, Peripheral Blood Stem Cell Transplantation Using Low Intensity Conditioning to Treat Patients With Chronic Granulomatous Disease Who Are Actively Infected

Chronic Granulomatous Disease (CGD) is an inherited disorder of neutrophil function.
Patients are profoundly immunocompromised and are plagued early in life with recurrent and
life threatening infections. The prognosis for CGD patients whose infection persists
despite appropriate medical and surgical intervention is extremely poor. Allogeneic stem
cell transplantation can cure CGD however the mortality of this procedure is high for
patients who are actively infected. Ongoing clinical trials at the NIH and elsewhere
suggest that the use of non-myeloablative conditioning for allogeneic stem cell
transplantation is safer and less toxic for patients who are free of infection at the time
of transplant. The goal of this phase II study is to investigate the safety and efficacy of
this novel approach to allogeneic stem cell transplantation for CGD patients who are
actively infected. Following a preparative regimen designed to provide intense
immunosuppression without myeloablation, patients will receive a peripheral blood stem cell
graft from an HLA identical parent or sibling. Donor T-cells will be infused
post-transplant if donor stem engraftment is unsatisfactory.

The end points of this study are engraftment, degree of donor-host chimerism, incidence of
acute and chronic GvHD, infection status, immune reconstitution, and transplant related
morbidity and mortality.

Inclusion Criteria



Ages 1-55 years.

DHR proven CGD: Includes gp91phox, p47phox, p22phox, and p67phox deficiency.

Must have an active, life threatening non-viral infection that persists despite adequate
and appropriate medical or surgical therapy (continued presence of pathogens on histology,
culture positivity or continued radiographic evidence of infection). Patients with a
progressive infectious process despite appropriate medical or surgical intervention may be
considered for expedited enrollment into the study.

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
molecular typing techniques.

Left ventricular ejection fraction greater than 35% predicted.

ECOG performance status of 0-3.


HLA identical sibling or parent donor.

Fit to receive G-CSF and give peripheral blood stem cells (weight over 18kg, normal blood
count, normotensive, no history of stroke, no history of severe heart disease).

Female carriers of X-linked must have greater than 30% normal neutrophils.

If donor is a sibling who is a minor, he/she is the oldest eligible sibling and no adults
are eligible donors.


Pregnant patients or donors.

Age greater than 55 years.

ECOG performance status of 4 or more. Psychiatric disorder or mental deficiency of the
patient or the donor sufficiently severe as to make compliance with PBSC transplantation
treatment unlikely, and making informed consent impossible.

Evidence of rapid deterioration due to progressive infection and/or organ damage.

Left ventricular ejection fraction: less than 35% predicted.

Creatinine Clearance less than 50. A maximum age adjusted serum creatinine will be used
for patients who are unable to provide an accurate 24 hour urine collection.

Serum bilirubin greater 4 mg/dl, Transaminases greater than 4 times the upper limit of

HIV positive (donor or recipient). 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.

Donor who is unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension,
history of stroke, history of heart disease, thrombocytopenia, massive splenomegaly).

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

October 2000

Completion Date:

November 2004

Related Keywords:

  • Chronic Granulomatous Disease
  • Fludarabine
  • Non-Myeloablative BMT
  • Immunodeficiency
  • Neutrophils
  • Oxidase
  • Engraftment
  • Graft-versus-host Disease
  • Cyclophosphamide
  • Donor Apheresis
  • Peripheral Blood Stem Cells
  • Therapy
  • Granulomatous Disease, Chronic
  • Granuloma



National Institute of Allergy and Infectious Diseases (NIAID) Bethesda, Maryland  20892