We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Busulfan, Cyclophosphamide, and Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00611351
Recruitment Status : Completed
First Posted : February 8, 2008
Last Update Posted : February 7, 2011
National Cancer Institute (NCI)
Information provided by:
University of Nebraska

Brief Summary:

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

Detailed Description:



  • 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)
Primary Purpose: Treatment
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
Primary Completion Date : February 2008
Study Completion Date : September 2008

Primary Outcome Measures :
  1. Transplantation-related mortality at 100 days post-transplantation
  2. Incidence of grade II-IV acute graft-versus-host-disease (GVHD)

Secondary Outcome Measures :
  1. Incidence of chronic GVHD
  2. Event-free survival
  3. Overall survival

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   19 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Pathologically confirmed diagnosis of 1 of the following:

    • Acute myeloid leukemia
    • Acute lymphocytic leukemia
    • Chronic myelogenous leukemia beyond first chronic phase (i.e., 2nd chronic phase, accelerated phase, or blast crisis)
    • Multiple myeloma
    • Myelodysplastic syndromes
    • Malignant lymphoma
    • Myelofibrosis
  • Requirement for myeloablative conditioning regimen confirmed by attending physician
  • Available donor must meet the following criteria:

    • HLA phenotypically identical unrelated donor by low, intermediate, or high resolution for HLA class I antigens, and by high resolution for HLA class II antigens

      • Matched at the A, B, and DRβ1 loci
      • Single HLA-A or HLA-B antigen mismatch allowed
    • Meets all National Marrow Donor Program or foreign registry criteria for allogeneic bone marrow/stem cell donors
    • Peripheral blood stem cells are the preferred product on this study but bone marrow is allowed


  • Karnofsky performance status 70-100%
  • DLCO ≥ 50% predicted
  • LVEF ≥ 45%
  • Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 65 mL/min
  • Serum total bilirubin ≤ 2.0 mg/dL
  • No active uncontrolled infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV infection
  • No chronic active hepatitis B or C or evidence of cirrhosis on liver biopsy


  • Not specified

Information from the National Library of Medicine

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

Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Principal Investigator: Marcel Devetten, MD University of Nebraska

Responsible Party: Marcel Devetten, M.D., UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier: NCT00611351     History of Changes
Other Study ID Numbers: 122-05
P30CA036727 ( U.S. NIH Grant/Contract )
First Posted: February 8, 2008    Key Record Dates
Last Update Posted: February 7, 2011
Last Verified: February 2011

Keywords provided by University of Nebraska:
graft versus host disease
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
untreated adult acute lymphoblastic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
stage III multiple myeloma
refractory multiple myeloma
de novo myelodysplastic syndromes
myelodysplastic/myeloproliferative disease, unclassifiable
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
secondary myelofibrosis
secondary acute myeloid leukemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Hodgkin lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Neoplasm Metastasis
Graft vs Host Disease
Primary Myelofibrosis
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions