Clinical Trial: Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis

Brief Summary:

RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and melphalan followed by a donor stem cell transplant works in treating young patients with resistant Langerhans cell histiocytosis.


Detailed Summary:

OBJECTIVES:

Primary

  • To determine the overall and disease-free survival of poor-risk pediatric patients with Langerhans cell histiocytosis at 1 and 3 years after reduced-intensity hematopoietic cell transplantation (RI-HCT).

Secondary

  • To determine day 100 transplantation-related mortality.
  • To determine the incidence of hematopoietic recovery and chimerism at day 100 and at 1 year post RI-HCT.
  • To determine the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD).
  • To determine the incidence of chronic GVHD.

OUTLINE: This is a multicenter study.

  • Non-myeloablative conditioning: Patients receive alemtuzumab intravenously (IV) over 2 hours on days -8 to -4, fludarabine phosphate IV over 30-60 minutes on days -7 to -3, and melphalan IV over 15-30 minutes on day -2. Some patients may receive anti-thymocyte globulin IV on days -6 to -2 instead of alemtuzumab.
  • Graft-versus-host disease prophylaxis and immunosuppression: Patients receive cyclosporine A (CSA) IV or orally 2-3 times daily beginning on day -3 and continuing until day 50 post transplantation, followed by a taper over 8 weeks in the absence of GVHD or donor lymphocyte infusion given for decreasing donor chimerism. Patients with mismatched donors (any source) and those receiving peripheral blood stem cells also receive mycophenolate mofetil (MMF) IV or orally 2-3 times daily beginning on day -3 and continuing
    Sponsor: Masonic Cancer Center, University of Minnesota

    Current Primary Outcome:

    • Overall Survival [ Time Frame: Year 1, Year 3 ]
      Count of patients alive at 1 and 3 years. Deaths from any cause are events. Surviving patients are censored at the date of last contact.
    • Disease-free Survival at 12 Months Post Transplantation [ Time Frame: Year 1 ]

      This outcome is defined as survival with resolution of LCH at 12 months post transplant.

      Unresolved disease for over 12 months post-transplant, progressive disease after this time period, recurrence of disease and death from any cause are considered events.

      Those who survive with resolution of disease are censored at the date of last contact.



    Original Primary Outcome:

    • Overall Survival
    • Disease-free Survival at 12 Months Post Transplantation


    Current Secondary Outcome:

    • Transplantation-related Death [ Time Frame: Day 100 ]
      Count of patients who died by day 100 related to the transplantation.
    • Neutrophil Engraftment [ Time Frame: Day 100 ]
      Incidence of neutrophil recovery and donor chimerism at Day 100.
    • Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD) [ Time Frame: Day 100 and Month 6 ]
      The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.
    • Incidence of Chronic GVHD [ Time Frame: Day 100 and Month 6 ]
      Occurrence of symptoms in any organ system fulfilling the criteria of limited or extensive chronic GvHD (Appendix III), among patients surviving > 90 days with evidence of engraftment. Patients without chronic GvHD will be censored at time of death or last follow-up.
    • Platelet Engraftment [ Time Frame: Day 100 ]
      Incidence of platelet recovery and donor chimerism at Day 100.
    • Incidence of Grade III-IV Acute Graft-versus-host-disease (GVHD) [ Time Frame: Day 100 and Month 6 ]
      The occurrence of skin, gastrointestinal or liver abnormalities fulfilling the criteria of Grades II, III and/or IV acute GVHD are considered events (Appendix II). Patients without acute GvHD will be censored at the time of death or last follow-up. Patients that survive <21 days and listed as not evaluable will be excluded. Patients receiving a second transplant will be censored at the time of second transplant.


    Original Secondary Outcome:

    • Transplantation-related mortality at day 100
    • Relapse
    • Hematopoietic recovery and chimerism at day 100 and at 1 year post transplantation
    • Neutrophil and platelet engraftment
    • Incidence of grades II-IV and III-IV acute graft-versus-host-disease (GVHD)
    • Incidence of Chronic GVHD


    Information By: Masonic Cancer Center, University of Minnesota

    Dates:
    Date Received: February 19, 2008
    Date Started: January 2007
    Date Completion:
    Last Updated: October 2, 2015
    Last Verified: July 2014