Matched Unrelated or Non-Genotype Identical Related Donor Transplantation For Chronic Granulomatous Disease
Condition: Chronic Granulomatous Disease
MeSH terms: Granuloma; Granulomatous Disease, Chronic
Intervention: Busulfan; Alemtuzumab; Cyclophosphamide; Fludarabine; Cyclosporine; Stem Cell Infusion
Intervention description: Days -9 through -6
1 mg/kg initially (based on weight); Day -5 through Day -2
Dose is based on weight:
Less than 15 kg: 3 mg
More than 15 kg to 30 kg: 5 mg
More than 30 kg: 15 mg; Days -5 through -2
50 mg/kg; Day -5 through Day -2
30 mg/m^2; Cyclosporine will be administered beginning Day -2. Initial dose will 5 mg/kg infused over 24 hours.; Stem Cell: Either bone marrow, cord blood, or peripheral blood stem cells may be used for stem cell transplantation. It is desired to infuse: for bone marrow, nucleated cells ≥ 4 X 10^8/kg recipient weight; for cord blood ≥ 3 X 10^7/kg nucleated cells; for peripheral blood stem cells ≥ 1 X 10^/kg CD34+ cells.
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Busulfan; Fludarabine; Alemtuzumab; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Healthy volunteers: No
Keywords: Stem Cell Transplant; Chronic Granulomatous Disease; Fludarabine; Busulfan; Cyclophosphamide

Summary:

      This study is for patients with chronic granulomatous disease (CGD), which is a disorder of
      the immune system that puts them at risk for severe infections. CGD is caused by a genetic
      defect that stops or prevents the white blood cells from killing certain bacteria and fungi.
      This condition cannot presently be cured by standard treatment with drugs or surgery.
      Medicine including antibiotics, antifungals, and interferon gamma, may help some patients
      with CGD; however even with continuous treatment, most patients with CGD will have chronic
      and recurrent infections. Transfusion of white blood cells may help overcome infection, but
      white cell transfusions lead to allergic reactions and fever and the benefit of transfusion
      lasts only a matter of hours. Ultimately, chronic infections can damage or injure the body
      organs. Injury to the lung or liver can lead to lung or liver failure and death. Medicines
      used to treat infection can damage body organs too. Infections may become resistant to
      antibiotic or antifungal treatment, and infections not responding to treatment can be deadly.

      It is now known that under specific conditions and with special treatment, blood stem cells
      (the cells that make blood) can be transplanted from one person to another. Stem cell
      transplantation has been done for patients with CGD who have a healthy sibling and who share
      the same immune type (HLA type) as the patient. Stem cell transplantation allows healthy or
      normal white cells from the stem cell donor to grow or develop in the patient's bone marrow.
      These healthy white cells can fight infection and prevent future infections for a patient
      with CGD.

      Patients on this study will receive stem cells from a related or unrelated donor. The donor
      will be closely matched to the patient's immune type but the donor is not a sibling. The
      reason this treatment is investigational is that we do not know the likelihood of benefit
      that the patient will receive. It is possible that they will have great benefit, like some of
      the patients who have been transplanted from a brother or sister. It is possible that the
      side-effects of treatment may be too severe so that the transplant won't work.

      The purpose of this research study is to evaluate whether or not patients with CGD treated
      with a stem cell transplant from a non-matched and/or non-related donor can have a good
      outcome from the procedure with an acceptable number of side-effects.
    

Eligibility criteria:

        INCLUSION CRITERIA:

        CGD patients as documented by an abnormal NBT assay in a male patient and/or abnormal NADPH
        enzyme mutation confirmed by genetic analysis with abnormal NBT.

        Patients must not have an HLA genotype identical donor.

        Patients must have a 5/6 or 6/6 HLA-matched unrelated donor or a 5/6 or 6/6 HLA
        phenotype-matched related donor.

        Patients must have had at least one serious infection characteristic of those manifested in
        patients with CGD.

        Patients must not have active infection. An active infection may include the following: 1)
        clinical findings consistent with an infection such as fever, cavitary organ lesions,
        osteomyelitis; 2) progression of presumed infection based upon findings of diagnostic
        imaging (two or more studies at least 1 month a part).

        No cumulative organ dysfunction that, in the estimation of the treating physicians, will
        diminish the patient's likelihood to survive this procedure.

        Negative pregnancy test for post-pubertal female patients.

        Echocardiogram shortening fraction >/= 28%.

        DLCO 50% or greater predicted or FEV1 >/= 50% predicted.

        EXCLUSION CRITERIA:

        Active or uncontrolled infection (e.g. lung infection, cavitary organ lesions,
        osteomyelitis).

        Markedly elevated C reactive protein or sedimentation rate relative to patient's baseline.

        Invasive bone or bone marrow disease.

        Lack of potential hematologic blood product donors in the past (related to McLeod
        phenotype).