Clinical Trial: Alemtuzumab, Fludarabine, and Busulfan Followed By Donor Stem Cell Transplant in Treating Young Patients With Hematologic Disorders

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

Official Title: Evaluation of Fludarabine, Busulfan and Alemtuzumab as a Reduced Toxicity Ablative Bone Marrow Stem Cell Transplant Regimen for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myelodyspl

Brief Summary:

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine and busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine together with methotrexate and methylprednisolone may stop this from happening.

PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and busulfan works when given before donor stem cell transplant in treating young patients with hematologic disorders.


Detailed Summary:

OBJECTIVES:

Primary

  • Determine the engraftment rate with reduced toxicity ablative conditioning regimen comprising alemtuzumab, fludarabine, and busulfan followed by allogeneic stem cell transplantation in pediatric patients with stem cell defects, marrow failure syndromes, hemoglobinopathy, severe immunodeficiency syndromes (nonsevere combined immunodeficiency disorders), myelodysplastic syndromes, or myeloid leukemia.

Secondary

  • Determine the acute reactions, incidence of infections, and rate of immune reconstitution in patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Conditioning regimen: Patients receive alemtuzumab IV over 6 hours on days -12 to -10, high-dose busulfan IV over 2 hours 4 times daily on days -9 to -6, and fludarabine IV over 30 minutes on days -5 to -2.
  • Allogeneic stem cell transplantation: Two days after the completion of conditioning regimen, patients undergo allogeneic bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover.

  • Graft-vs-host disease (GVHD) prophylaxis:

    • Most transplantations (bone marrow or peripheral blood stem cell transplantation): Patients receive cyclosporine IV continuously beginning on day -1 until at least day 50
      Sponsor: University of California, San Francisco

      Current Primary Outcome: Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation [ Time Frame: 6 weeks post-transplant ]

      Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences


      Original Primary Outcome:

      Current Secondary Outcome:

      • Treatment-related Mortality at 100 Days and 1 Year Post Transplantation [ Time Frame: 100 days and 1 year ]
      • Toxicity Grade ≥ 3 From Start of Conditioning Through the First Year Post Transplantation [ Time Frame: 1 year post-transplantation ]
      • Cytomegalovirus (CMV) Viral Infection and Disease Symptoms [ Time Frame: Up to one year post-transplant ]
        polymerase chain reaction testing for presence of CMV weekly until at least day +100 then every 2 weeks until T-cell reconstitution as defined by cluster of differentiation 4 (CD4) > 200 cells/mm3. Median time to T-cell reconstitution was 6 months.
      • Disease-free Survival With Correction of Disease at One Year Post Transplantation [ Time Frame: 1 year post-transplantation ]
        Patients deemed "alive and well" at follow-up timepoint later than 1-year post-transplantation


      Original Secondary Outcome:

      Information By: University of California, San Francisco

      Dates:
      Date Received: March 9, 2006
      Date Started: January 2005
      Date Completion:
      Last Updated: May 15, 2013
      Last Verified: May 2013