Alemtuzumab, Busulfan, and Cyclophosphamide Followed By a Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
RATIONALE: Monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as busulfan and cyclophosphamide, before a donor stem cell transplant helps stop the growth of cancer 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 tacrolimus and methotrexate after the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the best dose of alemtuzumab when given together with busulfan and cyclophosphamide followed by a donor stem cell transplant and to see how well it works in treating patients with hematologic cancer.
|Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases||Biological: alemtuzumab Drug: busulfan Drug: cyclophosphamide Drug: methotrexate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation||Phase 1 Phase 2|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Prospective Trial to Evaluate the Role of In Vivo T Cell Depletion by Campath® (Alemtuzumab) in Reduction of Transplant Related Mortality in Transplantation From HLA-Class I or Class II Mismatched, Unrelated Donors|
- Lowest Dose of Alemtuzumab Associated With Transplant-related Mortality [ Time Frame: Up to day 180 ]Lowest dose of alemtuzumab associated with transplant-related mortality at day 180
- Life-threatening Infection [ Time Frame: Up to 180 days ]
- Grades III-IV Acute Graft-vs-host Disease (GVHD) [ Time Frame: Up to 100 days ]
- Overall Survival [ Time Frame: Up to 1 year ]Count of surviving participants at 1 year
- Disease Relapse [ Time Frame: Up to 1 year ]Count of participants with disease relapse at 1 year
- Extensive Chronic GVHD [ Time Frame: Up to 1 year ]Count of participants with extensive chronic GVHD at 1 year
- Graft Failure [ Time Frame: Up to day 100 ]Count of participants with graft failure at day 100
|Study Start Date:||September 2007|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.
|Biological: alemtuzumab Drug: busulfan Drug: cyclophosphamide Drug: methotrexate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation|
- Identify the lowest dose of alemtuzumab that is associated with day 180 transplant-related mortality ≤ 45%.
- Determine the incidence of life-threatening infection in patients receiving this treatment.
- Determine the incidence of grades III-IV acute graft-vs-host disease (GVHD) in patients receiving this treatment.
- Determine the survival at 1 year in patients receiving this treatment.
- Determine the incidence of disease relapse at 1 year in patients receiving this treatment.
- Determine the incidence of extensive chronic GVHD at 1 year in patients receiving this treatment.
- Determine the incidence of graft failure at day 100 in patients receiving this treatment.
- Chemotherapy: Patients receive alemtuzumab IV over 2 hours on days -10 to -6, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV on days -3 and -2.
- Peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic filgrastim (G-CSF)-mobilized PBSC transplantation on day 0.
- Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -1 to 50 and methotrexate IV on days 1, 3, 6, and 11.
After completion of study therapy, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00555048
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98104-1024|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109-1023|
|Principal Investigator:||Ann E. Woolfrey, MD||Fred Hutchinson Cancer Research Center|