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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00611351
First received: February 7, 2008
Last updated: February 3, 2011
Last verified: February 2011
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Transplantation-related mortality at 100 days post-transplantation [ Designated as safety issue: Yes ]
  • Incidence of grade II-IV acute graft-versus-host-disease (GVHD) [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of chronic GVHD [ Designated as safety issue: Yes ]
  • Event-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: June 2005
Study Completion Date: September 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

OUTLINE:

  • 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.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • Not specified
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00611351

Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Marcel Devetten, MD University of Nebraska
  More Information

Additional Information:
No publications provided

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, UNMC-12205
Study First Received: February 7, 2008
Last Updated: February 3, 2011
Health Authority: United States: Institutional Review Board

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:
Primary Myelofibrosis
Neoplasm Metastasis
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Graft vs Host Disease
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Lymphoma
Leukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Lymphatic Diseases

ClinicalTrials.gov processed this record on September 16, 2014