NCT00301834

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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 description

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 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 weekly taper. After transplantation, patients are followed periodically for up to 20 years. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Conditions

• Congenital Amegakaryocytic Thrombocytopenia
• Diamond-blackfan Anemia
• Leukemia
• Myelodysplastic Syndromes
• Severe Congenital Neutropenia

Interventions

Type	Name	Description
BIOLOGICAL	alemtuzumab
DRUG	busulfan
DRUG	cyclosporine
DRUG	fludarabine phosphate
DRUG	methotrexate
DRUG	methylprednisolone
PROCEDURE	allogeneic bone marrow transplantation
PROCEDURE	allogeneic hematopoietic stem cell transplantation
PROCEDURE	peripheral blood stem cell transplantation
PROCEDURE	umbilical cord blood transplantation

Timeline

• Start date: 2005-01-01
• Primary completion: 2011-09-01
• Completion: 2011-09-01
• First posted: 2006-03-13
• Last updated: 2017-09-28
• Results posted: 2013-05-16

Locations

2 sites across 1 country: United States