Clinical Trial: Observational Study to Evaluate Allogeneic HSCT Outcomes for Cerebral Adrenoleukodystrophy (CALD)

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

Official Title: A Prospective and Retrospective Data Collection Study to Evaluate Outcomes in Males ≤17 Years of Age Undergoing Allogeneic Hematopoietic Stem Cell Transplantation for the Treatment of Cerebral <

Brief Summary: Study ALD 103 is a multi-site, global, data collection study that is designed to evaluate safety and efficacy of allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with CALD aged 17 or younger.

Detailed Summary:

Study ALD-103 is a multi-site, global, prospective and retrospective data collection study that is designed to evaluate outcomes of allo-HSCT in male subjects ≤17 years of age with CALD. Retrospective subjects will be ≤17 years of age at the time of treatment; prospective subjects will be ≤17 years of age at the time of consent. This is an observational study that does not involve the use of an investigational drug or medicinal product. It allows for collection of specific data points related to the allo-HSCT procedures and outcomes. Suitability for allo-HSCT and the choice of the treatment protocol utilized for these subjects will be determined by the subjects' treating physicians as per their institutional policies/protocols and other local treatment guidelines. Procedures to be performed will be those according to institutional protocols and the accepted management of CALD, including supportive care, choice of graft source, allo-HSCT protocol, prophylaxis, and management of graft-versus-host disease (GVHD).

Subjects will be monitored from Screening before allo-HSC infusion, through their Month 48 Visit after allo-HSC infusion. Follow-up will include monitoring of outcome measures at Months 1, 2, 3, 6, 9, 12, 18, 24, 36, and 48 after allo-HSC infusion (prospective analysis).

In addition to the subjects in the prospective analysis, subjects who received an allo-HSCT on or after January 1, 2013 who will be available for at least the Month 24 visit (24 ± 1 months after allo-HSC infusion) may also be enrolled and followed through their Month 48 Visit after their most recent allo-HSC infusion (partial prospective analysis and retrospective analysis, as applicable).


Sponsor: bluebird bio

Current Primary Outcome:

  • Incidence of transplant-related mortality (TRM), defined as death due to any transplantation-related cause other than disease relapse. [ Time Frame: 1-48 (± 2) months post-transplant ]
  • Kinetics of engraftment [ Time Frame: 42 days post-transplant ]
    Kinetics of engraftment will be addressed by analyzing frequency of both neutrophil and platelet engraftment
  • Frequency of primary donor-derived chimerism of ≥50% [ Time Frame: by 100 days post-allo-HSC infusion ]
  • Frequency of engraftment failure or allograft rejection [ Time Frame: 1-48 (± 2) months post-allo-HSC infusion ]
  • Frequency and severity of CTCAE ≥Grade 3 AEs, CTCAE ≥Grade 3 infections, and all SAEs [ Time Frame: Day 0 (allo HSC infusion) up to and including the 48 Months visit ]

    Frequency and severity of adverse events (AEs) as follows:

    ≥Grade 3 AEs; AEs related to ≥Grade 2 acute GVHD, and all AEs related to chronic GVHD

  • Incidence of ≥Grade II acute GVHD and of chronic GVHD [ Time Frame: 1-48 (± 2) months post-all HSC infusion ]
  • Number of emergency room visits [ Time Frame: 1-48 (± 2) months post-all HSC infusion ]
  • Number and duration of intensive care unit stay [ Time Frame: 1-48 (± 2) months post-all HSC infusion ]
  • Number and duration of in-patient hospitali

    Original Primary Outcome:

    • Mortality [ Time Frame: 1-180 days post-transplant ]
      • Incidence of transplant-related mortality through 100 and 180 days post-allo hematopoietic stem cell (HSC) infusion
    • Incidence of successful of HSC engraftment [ Time Frame: 42 and 100 days post-transplant ]

      •Incidence of successful of HSC engraftment, as measured by:

      • achieving an absolute neutrophil count (ANC) ≥500 cells/mm3 for 3 consecutive days by 42 days post-HSC infusion
      • achieving primary donor-derived chimerism of ≥50% by 100 days post-HSC infusion
    • Kinetics of engraftment [ Time Frame: 1-24 months post-transplant ]
      •Kinetics of engraftment (i.e., time to achieve an ANC≥500 cells/mm3 for 3 consecutive days post-HSC infusion)
    • Frequency and severity of adverse events [ Time Frame: 1-24 months post-transplant ]

      •Frequency and severity of adverse events (AEs) as follows:

      • Grade 2 from Day 0 (allo-HSC infusion) up to and including Month 12 visit
      • Grade 3 from the day after the 12 Month Visit up to and including Month 24 Visit


    Current Secondary Outcome:

    • Frequency of Major Functional Disabilities (MFDs), defined as any of the following: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement. [ Time Frame: 1-48 (± 2) months post-all HSC infusion ]
    • Change from Baseline in Loes score [ Time Frame: 1-48 (± 2) months post-all HSC infusion ]
    • Change from Baseline in Neurological Function Score (NFS) [ Time Frame: 1-48 (± 2) months post-allo HSC infusion ]
    • Frequency and timing of resolution of gadolinium enhancement on MRI, if applicable [ Time Frame: 1-48 (± 2) months post-allo HSC infusion ]
    • MFD-free survival [ Time Frame: 48 (± 2) months post-allo HSC infusion ]
    • Overall survival [ Time Frame: 48 (± 2) months post-allo HSC infusion ]


    Original Secondary Outcome:

    • Incidence of Major Functional Disabilities [ Time Frame: 1-24 monthspost-transplant ]
      • Incidence of Major Functional Disabilities (MFDs) (as measured by Neurological Function Score [NFS]; defined as any of the following: loss of communication, cortical blindness, tube feeding, total incontinence, wheelchair dependence, or complete loss of voluntary movement)
    • Change from Baseline in Loes score [ Time Frame: 1-24 months post-transplant ]
    • Change from Baseline in NFS [ Time Frame: 1-24 months post-transplant ]
    • Frequency and timing of resolution of gadolinium enhancement on MRI, if applicable [ Time Frame: 1-24 months post-transplant ]
    • MFD-free survival [ Time Frame: 1-24 months post-transplant ]
    • Overall survival [ Time Frame: 1-24 months post-transplant ]


    Information By: bluebird bio

    Dates:
    Date Received: July 28, 2014
    Date Started: December 2014
    Date Completion: May 2021
    Last Updated: May 11, 2017
    Last Verified: May 2017