Clinical Trial: Patients Treated for Chronic Granulomatous Disease (CGD) Since 1995

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Analysis of Patients Treated for Chronic Granulomatous Disease Since January 1, 1995

Brief Summary: Chronic granulomatous disease (CGD) is an inherited immune system abnormality in which bone marrow transplantation has been shown to be curative. However the risks of transplantation are high and not all patients with CGD may need to undergo this high risk procedure. This study will determine the long term medical condition and daily functioning of patients with CGD after a transplant and if possible, compare these results to patients who do not undergo a transplant.

Detailed Summary: This multi-center study combines a longitudinal and cross-sectional evaluation (both retrospectively and prospectively) of subjects with confirmed CGD who have already received hematopoietic cell transplant (HCT) since 1995 or who will receive HCT during the study period. This study will investigate which subjects benefit most from HCT, and the overall outcomes in CGD patients with and without transplant. The study aims to identify variables contributing to best outcomes of HCT in subjects with CGD.
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome: Death [ Time Frame: HCT to date of death, up to an expected average of 3 years ]

The event analyzed is death from any cause. The time from HCT to death or last follow up will be analyzed. Cause of death will also be collected. Surviving patients will be censored at the time of last observation.


Original Primary Outcome:

  • Longitudinal Analysis: overall survival of transplanted subjects. [ Time Frame: an expected average of 3 years ]
    The event analyzed is death from any cause. The time from HCT to death or last follow up will be analyzed. Cause of death will also be collected. Surviving patients will be censored at the time of last observation.
  • Cross-sectional Analysis: Infection History for Preceding 1-Year Duration [ Time Frame: an expected average of 3 years ]
    up to 1 year prior to cross-sectional visit and subject at least 3 years post-transplant or postdiagnosis


Current Secondary Outcome:

  • Engraftment [ Time Frame: an expected average of 3 years ]
    Engraftment will be measures in whole blood using either fluorescent in situ hybridization (FISH) for sex chromosomes or short tandem repeat polymerase chain reaction or PCR (STRs) in whole blood.
  • Quality of Life Measures [ Time Frame: an expected average of 3 years ]

    Age appropriate testing will be performed at the cross-sectional visit in patients surviving at least two years posttransplant:

    • Pediatrics quality of life (QL) Family Impact Module, Parent Report
    • Peds QL Infant Scales Module (ages 1-24 months), Parent Report
    • Peds QL Generic Core Scales for Toddlers (ages 2-4 yr), Parent Report
    • Peds QL Generic Core Scales (ages 5-25 yr), Child/Parent Reports
    • Peds QL Transplant Module
    • Standard Form (SF)-36 (adult)
    • Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT BMT) (adult)
  • Infections [ Time Frame: an expected average of 3 years ]
    CGD or transplant-related and transplant-related infection
  • Autoimmune or inflammatory complications [ Time Frame: an expected average of 3 years ]
    - For HCT subjects, inflammation (inflammatory complications) includes chronic graft-versus-host disease (GVHD)


Original Secondary Outcome:

  • Longitudinal Analysis: Survival of HCT Subjects vs. Conventional Therapy Subjects [ Time Frame: an expected average of 3 years ]
    For the comparison of HCT subjects with conventional therapy subjects the time to this event is time from birth, where all subjects transplanted and non-transplanted will have been born in or after 1988, to death or last contact. For this analysis patients will be stratified by residual oxidase activity into oxidase positive or oxidase null groups, as measured or as predicted from CGD subtype or mutation type. Because all CGD patients in the transplant group must by definition be alive at transplant, comparison of time to death or last follow up vs. the non-transplant group will use left truncation to adjust for survivor bias. Analyses will be conducted conditional on survival to the youngest age at transplant for the HCT group. Cause of death will also be collected. Surviving patients will be censored at the time of last observation.
  • Longitudinal Analysis: Prevalence of Recent Infection or Inflammatory Complication of HCT Subjects vs. Conventional Therapy Subjects [ Time Frame: an expected average of 3 years ]
    The prevalence of any one or more of the following complications within one year of last contact date will be used to assess outcome for an individual patient. Transplant patients must be three years or more post-HCT. Conventional therapy subjects must be three years or more post-diagnosis of CGD.
  • Longitudinal Analysis: Event-Free Survival [ Time Frame: an expected average of 3 years ]

    Events analyzed include:

    • Death
    • CGD-related infection
    • Autoimmune or inflammatory complications (new onset)
    • Chronic Graft-Versus-Host Disease (GVHD)
  • Longitudinal Analysis: Granulocyte Function [ Time Frame: an expected average of 3 years ]

    DHR assay and/or Ferricytochrome C production will be used in all transplanted patients.

    Granulocyte reconstitution is defined by achieving 15% or higher oxidase-corrected granulocytes (15% or higher of cells with normal oxidase activity) at any time-point after transplant.

    Granulocyte partial reconstitution is defined as <15% but ≥5% oxidase-corrected granulocytes (<15% but ≥5% of cells with normal oxidase activity) at and after Day 100 following HCT.

  • Longitudinal Analysis: Engraftment [ Time Frame: an expected average of 3 years ]
    We will obtain and measure engraftment in whole blood using either fluorescent in situ hybridization (FISH) for sex chromosomes or short tandem repeat (STR) PCR in whole blood.
  • Longitudinal Analysis: Infection [ Time Frame: an expected average of 3 years ]
    Infection will be defined as any infection that requires hospitalization and/or a minimum of 16 days of therapeutic antibiotics. This does not include antibiotics given as prophylaxis.
  • Longitudinal Analysis: Incidence of Infections in HCT Subjects vs. Conventional Therapy Subjects [ Time Frame: an expected average of 3 years ]
    The rate of infections during the year prior to last contact will be compared between HCT subjects and non-transplant controls. HCT subjects must be at least three years from HCT at last contact, while non-transplant controls must be at least 3 years from diagnosis of CGD.
  • Longitudinal Analysis: Autoimmune Disease and Inflammatory Complications Post-HCT [ Time Frame: an expected average of 3 years ]

    Autoimmune disease will be defined as any inflammatory or autoimmune phenomena previously reported to be associated with CGD- or related to transplant and requiring treatment with immunosuppression of at least a dose of 0.2mg/kg/day of oral prednisone or equivalent to achieve either partial or complete resolution of the symptoms.

    Autoimmune/inflammatory disease reported in association with CGD include, but are not limited to

    • Inflammatory bowel disease (biopsy proven)
    • Strictures of hollow organs
    • Pulmonary disease (restrictive)
    • SLE and lupus like conditions
    • Sarcoid
    • Rheumatoid and juvenile arthritis
    • IgA Nephropathy
    • Antiphospholipid syndrome
    • Idiopathic thrombocytopenia (ITP)
  • Longitudinal Analysis: Prevalence of Autoimmune Disease and Inflammatory Complications in HCT Subjects vs. Conventional Therapy Subjects [ Time Frame: an expected average of 3 years ]