Busulfan, Cyclophosphamide, and Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
Information source: University of Nebraska
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Secondary Myelofibrosis
Intervention: anti-thymocyte globulin (Biological); busulfan (Drug); cyclophosphamide (Drug); mycophenolate mofetil (Drug); tacrolimus (Drug); polymerase chain reaction (Genetic); polymorphism analysis (Genetic); flow cytometry (Other); laboratory biomarker analysis (Other); pharmacogenomic studies (Other); pharmacological study (Other); allogeneic bone marrow transplantation (Procedure); allogeneic hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure)
Phase: Phase 2
Status: Completed
Sponsored by: University of Nebraska Official(s) and/or principal investigator(s): Marcel Devetten, MD, Principal Investigator, Affiliation: University of Nebraska
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.
Clinical Details
Official title: Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation With a Conditioning Regimen of Targeted Busulfan, Cyclophosphamide, and Thymoglobulin
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Transplantation-related mortality at 100 days post-transplantationIncidence of grade II-IV acute graft-versus-host-disease (GVHD)
Secondary outcome: Incidence of chronic GVHDEvent-free survival Overall survival
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
Minimum age: 19 Years.
Maximum age: 65 Years.
Gender(s): Both.
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
Locations and Contacts
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: June 2005
Last updated: February 3, 2011
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