Clinical Trial: Reduced Intensity Conditioning for Umbilical Cord Blood Transplant in Pediatric Patients With Non-Malignant Disorders

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pilot Study of Reduced Intensity Conditioning in Pediatric Patients <21 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood Transplantation

Brief Summary: The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

Detailed Summary:

Myeloablative doses of chemotherapy and/or radiation therapy are employed with the primary purpose of eradicating malignant cells. Additionally, these regimens exert varying degree of immunosuppression/immunoablation that aids in reducing the likelihood of rejection by host hematopoietic cells. However, myeloablative /immunoablative regimens have also been associated with significant regimen related toxicity (RRT) and regimen related mortality (RRM) that may cause death in up to 20% of patients and significantly higher rate of severe organ dysfunction or failure. While most of these RRT occur typically in the first 100 days [ e.g. VOD (veno occlusive disease), pulmonary or intracranial hemorrhage, multiorgan failure (MOF)], there are significant long term toxicities of TBI and/or chemotherapy including growth impairment, gonadal dysfunction/failure, hypothyroidism, cataracts, neurocognitive impairment, and second malignancies.

The primary objective is to determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor chimerism at 180 days) following reduced intensity conditioning (RIC) regimens in pediatric patients < 21 years receiving cord blood transplantation for non-malignant disorders.

The secondary objectives are:

  • To describe the pace of neutrophil and platelet recovery
  • To evaluate the pace of immune reconstitution.
  • To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant
  • To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD
  • To describe the incidence
    Sponsor: Duke University

    Current Primary Outcome: Determine the Feasibility of Attaining Acceptable Rates of Donor Cell Engraftment (>25% Donor Cells at 180 Days) Following RIC Regimens in Children < 21 Years Receiving UCBT for Non-malignant Disorders. [ Time Frame: 180 days post transplant ]

    Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders.


    Original Primary Outcome: Determine the feasibility of attaining acceptable rates of donor cell engraftment (>25% donor cells at 180 days) following reduced intensity conditioning regimens in children < 21 years receiving cord blood transplant for non-malignant disorders. [ Time Frame: 180 days post transplant ]

    Current Secondary Outcome:

    • To Describe the Pace of Neutrophil Recovery [ Time Frame: 42 days post transplant ]
      Neutrophil recovery was defined as the first day of an absolute neutrophil count (ANC) more than 500/uL for 3 consecutive days not secondary to granulocyte infusions
    • To Evaluate the Pace of Immune Reconstitution. [ Time Frame: 1 year post transplant ]
      Immune reconstitution after RIC in UCBT was described. CD4 count is a standard measure of immune reconstitution and is described here. Additional data is available upon request.
    • To Determine the Overall Survival at day180 Post-transplant [ Time Frame: 180 days ]
      To determine the overall survival at day180 post-transplant: determined by Kaplan Meier survival analysis
    • To Describe Incidence of Acute Graft Versus Host Disease (GVHD) (II - IV) [ Time Frame: 100 days post transplant ]
      To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) : measured by cumulative incidence analysis
    • To Describe the Incidence of Grade 3-4 Organ Toxicity [ Time Frame: 2 years post transplant ]
    • To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure [ Time Frame: at least 2 years post transplant ]
    • To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant [ Time Frame: 2 years post transplant ]
    • To Describe the Pace of Platelet Recovery [ Time Frame: 180 days post transplant ]
      Platelet engraftment was defined as the first day of platelet counts more than 50,000/uL for 7 consecutive days without transfusions


    Original Secondary Outcome:

    • To describe the pace of neutrophil and platelet recovery [ Time Frame: 180 days post transplant ]
    • To Evaluate the Pace of Immune Reconstitution. [ Time Frame: 2 years post transplant ]
    • To determine the treatment related mortality, overall survival and disease free survival by days 100 and 180 post-transplant [ Time Frame: 180 days ]
    • To describe incidence of acute Graft Versus Host Disease (GVHD) (II - IV) and chronic extensive GVHD [ Time Frame: 2 years post transplant ]
    • To Describe the Incidence of Grade 3-4 Organ Toxicity [ Time Frame: 2 years post transplant ]
    • To Evaluate Long-term Complications, Such as Sterility, Endocrinopathy, and Growth Failure [ Time Frame: at least 2 years post transplant ]
    • To Evaluate the Incidence of Late Graft Failures at 2 Years Post-transplant [ Time Frame: 2 years post transplant ]


    Information By: Duke University

    Dates:
    Date Received: August 28, 2008
    Date Started: October 2008
    Date Completion:
    Last Updated: July 23, 2014
    Last Verified: July 2014