Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT ID: NCT00322101
Last Updated: 2014-10-31
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
25 participants
INTERVENTIONAL
2006-01-31
2014-10-31
Brief Summary
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PURPOSE: This phase III trial is studying low-dose conditioning to see how well it works compared to high-dose conditioning followed by peripheral blood stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia
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Detailed Description
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I. Determine whether the conditioning intensity affects outcomes after HCT in patients with MDS or AML who have \< 5% marrow myeloblasts at the time of HCT.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I (Nonmyeloablative regimen):
CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.
GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.
Arm II (Myeloablative regimen):
CONDITIONING: Patients are assigned to 1 of 2 treatment groups.
Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.
Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.
TRANSPLANTATION: Patients undergo PBSC infusion on day 0.
GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm I (Nonmyeloablative regimen)
CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0.
GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96.
total-body irradiation
Radiation
mycophenolate mofetil
Given orally
cyclosporine
Given IV or orally
fludarabine phosphate
Given IV
peripheral blood stem cell transplantation
Undergo transplantation
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantation
laboratory biomarker analysis
Correlative studies
cytogenetic analysis
Correlative studies
flow cytometry
Correlative studies
fluorescence in situ hybridization
Correlative studies
pharmacological study
Correlative studies
polymorphism analysis
Correlative studies
Arm II (Myeloablative regimen)
CONDITIONING: Patients are assigned to 1 of 2 treatment groups.
Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.
Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.
TRANSPLANTATION: Patients undergo PBSC infusion on day 0.
GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantation
cyclophosphamide
Given IV
busulfan
Given IV or orally
fludarabine phosphate
Given IV
peripheral blood stem cell transplantation
Undergo transplantation
laboratory biomarker analysis
Correlative studies
flow cytometry
Correlative studies
fluorescence in situ hybridization
Correlative studies
pharmacological study
Correlative studies
polymorphism analysis
Correlative studies
tacrolimus
Given IV or orally
methotrexate
Given IV
Interventions
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total-body irradiation
Radiation
allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantation
cyclophosphamide
Given IV
mycophenolate mofetil
Given orally
busulfan
Given IV or orally
cyclosporine
Given IV or orally
fludarabine phosphate
Given IV
peripheral blood stem cell transplantation
Undergo transplantation
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantation
laboratory biomarker analysis
Correlative studies
cytogenetic analysis
Correlative studies
flow cytometry
Correlative studies
fluorescence in situ hybridization
Correlative studies
pharmacological study
Correlative studies
polymorphism analysis
Correlative studies
tacrolimus
Given IV or orally
methotrexate
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* De novo acute myelogenous leukemia (AML) beyond first remission
* Intermediate or high risk de novo AML in first complete response (at FHCRC unrelated donor recipients only)
* Chemotherapy required prior to HCT for all patients:
* A) Interval between start of a cycle of cytoreductive chemotherapy and infusion of donor stem cells must be at least 30 days; chemotherapy received for disease maintenance will be allowed during this time period
* B) All patients must have \< 5% myeloblasts based on marrow morphology performed within 21 days prior to start of conditioning regimen and at least 3-4 weeks after the start of pre-transplant cytoreductive chemotherapy
* C) All patients must have no circulating peripheral blood myeloblasts present based on morphologic analysis
* Age 65 years or under for patients with related donors; age 60 years or under for patients with unrelated donors
* HCT-Specific Comorbidity Index Score (HCT-CI) \< 3
* Related donor (age \> 12 years, nonsyngeneic) or unrelated donor, HLA phenotypically or genotypically identical at the allele level at A,B,C,DRQ1, and CBQ1
* DONOR: Related or unrelated donors who are genotypically or phenotypically matched by high resolution HLA typing (HLA-A, B, C, DRB1, and DQB1); class 1 single allele mismatch allowed
* DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A\*0101 and the donor is A\*0201, and this type of mismatch is not allowed
* DONOR: A positive anti-donor cytotoxic crossmatch or flow cytometric assay is an absolute donor exclusion at FHCRC/SCCA
* DONOR: Age \>= 12 years
* DONOR: Donors must consent to PBSC mobilization with G-CSF and leukaphereses; bone marrow as a source of stem cells will not be allowed
* DONOR: Donor must have adequate veins for leukaphereses or agree to placement of central venous catheter (femoral, subclavian)
Exclusion Criteria
* Fungal infections with radiographic progression after appropriate therapy for greater than one month
* Organ dysfunction
* Symptomatic coronary artery disease or ejection fraction \< 35%
* DLCO \< 65%, FEV1 \< 65% or receiving supplementary continuous oxygen
* Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, and symptomatic biliary disease will be excluded
* Karnofsky Performance Score \< 70
* Lansky-Play Performance Score \< 70 for pediatric patients
* Life expectancy severely limited (\< 2 years) by disease other than MDS/AML
* Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment
* Patients with active non-hematological malignancies except:
* A) Patients with follicular or low grade lymphoma will be eligible as long as they have not and do not require active treatment for control of their disease
* B) Patients with localized non-melanoma skin malignancies
* Patients with poorly controlled hypertension who are unable to have blood pressure stabilized below 150/90 mm Hg on standard medication
* Females who are pregnant or breastfeeding
* Patients with systemic, uncontrolled infections
* Active CNS disease as identified by positive CSF cytospin
* DONOR: Identical twin
* DONOR: Age \< 12 years
* DONOR: Pregnancy
* DONOR: HIV seropositivity
* DONOR: Inability to achieve adequate venous access
* DONOR: Known adverse reaction to G-CSF
65 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Fred Hutchinson Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Bart Scott
Role: PRINCIPAL_INVESTIGATOR
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Locations
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HealthOne Presbyterian St. Lukes Medical Center
Denver, Colorado, United States
Emory University
Altanta, Georgia, United States
Weill Cornell University
New York, New York, United States
University of Utah
Salt Lake City, Utah, United States
Veterans Administration Center-Seattle
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Medical College Wisconsin
Milwaukee, Wisconsin, United States
Technical University Dresden
Dresden, Saxony, Germany
Countries
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Other Identifiers
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NCI-2010-00737
Identifier Type: REGISTRY
Identifier Source: secondary_id
1992.00
Identifier Type: -
Identifier Source: org_study_id
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