Busulfan, Cyclophosphamide, and Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
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|ClinicalTrials.gov Identifier: NCT00611351|
Recruitment Status : Completed
First Posted : February 8, 2008
Results First Posted : April 3, 2018
Last Update Posted : April 3, 2018
RATIONALE: Giving chemotherapy before a donor bone marrow transplant or peripheral stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain 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 mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving busulfan together with cyclophosphamide and antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer.
|Condition or disease||Intervention/treatment||Phase|
|Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Secondary Myelofibrosis||Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: mycophenolate mofetil Drug: tacrolimus Genetic: polymerase chain reaction Genetic: polymorphism analysis Other: flow cytometry Other: laboratory biomarker analysis Other: pharmacogenomic studies Other: pharmacological study Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation||Phase 2|
- To determine the incidence of grade II-IV acute graft-versus-host disease in patients with hematologic cancer or other diseases treated with a myeloablative conditioning regimen comprising targeted (steady-state concentration of 800-1,000 ng/mL) busulfan, cyclophosphamide, and anti-thymocyte globulin followed by matched unrelated donor allogeneic hematopoietic stem cell transplantation.
- To determine the day +100 transplantation-related mortality in these patients.
- To determine the effect of cyclophosphamide pharmacokinetic parameters on day +100 transplantation-related mortality in these patients.
- To determine the ability of low-dose anti-thymocyte globulin administered on day +5 to induce activation-induced cell death of activated donor lymphocytes.
- To determine the incidence of chronic graft-versus-host disease in patients treated with this regimen.
- To determine event-free and overall survival of patients treated with this regimen.
- To evaluate pharmacogenomic associations between genetic polymorphisms in drug disposition enzymes with the pharmacokinetics of busulfan and cyclophosphamide.
- Myeloablative conditioning regimen: Patients receive busulfan IV over 2 hours on days -8 to -5; cyclophosphamide IV over 4 hours on days -3 to -2; and anti-thymocyte globulin IV over 6 hours on day -3 and then over 4 hours on days -2, -1, and 5.
- Allogeneic hematopoietic stem cell transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell infusion on day 0.
- Graft-versus-host-disease prophylaxis: Patients receive tacrolimus IV continuously or orally on days 6 to150, followed by an even taper to day 180 in the absence of graft-versus-host-disease. Patients also receive mycophenolate mofetil IV or orally beginning on day 6 and continuing to day 28.
Patients undergo blood collection periodically during study for pharmacokinetic, pharmacogenomic, and other translational studies. Genomic DNA extracted from blood samples is analyzed by polymerase chain reaction for genetic polymorphisms in cyclophosphamide/busulfan disposition enzymes. Activated donor lymphocytes are assessed using flow cytometry to measure activation-induced cell death, as reflected by apoptosis in activated T cells. Chimerism on or around day 100 is also assessed using fluorescence in situ hybridization analysis and DNA fingerprinting.
After completion of study treatment, patients are followed periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||5 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation With a Conditioning Regimen of Targeted Busulfan, Cyclophosphamide, and Thymoglobulin|
|Study Start Date :||June 2005|
|Actual Primary Completion Date :||February 2008|
|Actual Study Completion Date :||September 2008|
Experimental: Unrelated Donor Allogeneic
Matched unrelated donor allogeneic stem cell transplantation with a conditioning regimen of targeted busulfan, cyclophosphamide and thymoglobulin.
Biological: anti-thymocyte globulin
Drug: mycophenolate mofetil
Genetic: polymerase chain reaction
Genetic: polymorphism analysis
Other: flow cytometry
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
- Transplantation-related Mortality at 100 Days Post-transplantation [ Time Frame: at the 100 days post-transplant ]
- Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD) [ Time Frame: at day 100 post transplantation ]
- Overall Survival [ Time Frame: 2 years post transplant ]
- Event-free Survival [ Time Frame: 2 years post transplant ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00611351
|Principal Investigator:||Marcel Devetten, MD||University of Nebraska|