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 Myelodysplastic Syndrome (MDS)/Leukemia
- 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.
- 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 followed by a taper at either 2 months, 9 months, or 1 year in the absence
of GVHD. Patients also receive methotrexate on days 1, 3, and 6.
- Umbilical cord blood transplantation: Patients receive cyclosporine as in most
transplantations, and methylprednisolone IV twice daily on days 0-21 followed by a
After transplantation, patients are followed periodically for up to 20 years.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation
Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences
6 weeks post-transplant
Morton J. Cowan, MD
University of California, San Francisco
United States: UCSF Cancer Research Center protocol Review Committee
|University of Wisconsin Paul P. Carbone Comprehensive Cancer Center||Madison, Wisconsin 53792-6164|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|