Trial record 4 of 1378 for:    "Myelodysplastic syndromes"

Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Bart Scott, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00322101
First received: May 2, 2006
Last updated: August 21, 2013
Last verified: August 2013
  Purpose

RATIONALE: Giving chemotherapy, such as fludarabine phosphate, busulfan, and cyclophosphamide, and total-body radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy 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. It is not yet known whether low-dose chemotherapy and total-body radiation therapy is more effective than high-dose chemotherapy in treating patients with myelodysplastic syndrome or acute myeloid leukemia.

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


Condition Intervention Phase
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
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)
Childhood Acute Myeloid Leukemia in Remission
Childhood Myelodysplastic Syndromes
de Novo Myelodysplastic Syndromes
Myelodysplastic Syndrome With Isolated Del(5q)
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Acute Myeloid Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Radiation: total-body irradiation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: cyclophosphamide
Drug: mycophenolate mofetil
Drug: busulfan
Drug: cyclosporine
Drug: fludarabine phosphate
Procedure: peripheral blood stem cell transplantation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Other: laboratory biomarker analysis
Genetic: cytogenetic analysis
Other: flow cytometry
Genetic: fluorescence in situ hybridization
Other: pharmacological study
Genetic: polymorphism analysis
Drug: tacrolimus
Drug: methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplant Conditioning in Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: At 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: After stem cell infusion to date of last follow up. ] [ Designated as safety issue: Yes ]
    IWG criteria was used to determine disease progression

  • Non-relapse Mortality [ Time Frame: At 100 days ] [ Designated as safety issue: Yes ]
  • Donor Cell Engraftment [ Time Frame: After stem cell infusion to day 28 ] [ Designated as safety issue: Yes ]
    Chimerism analysis was performed in patients who recieved nonmyeloablative tranplsnat. In this group the definition of engraftment was a CD3 count greater than 50%. In the myeloablative group, engraftment was defined as an absolute neutrophil count greater than 50%.

  • Incidence of Disease Progression/Relapse [ Time Frame: After stem cell infusion to date of last follow up. ] [ Designated as safety issue: No ]
    Disease progression/relapse was defined by IWG criteria

  • Incidence and Severity of Acute and Chronic Graft-vs-host Disease [ Time Frame: After transplantation ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: January 2006
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Radiation: total-body irradiation
Radiation
Other Name: TBI
Drug: mycophenolate mofetil
Given orally
Other Names:
  • Cellcept
  • MMF
Drug: cyclosporine
Given IV or orally
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Procedure: peripheral blood stem cell transplantation
Undergo transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantation
Other: laboratory biomarker analysis
Correlative studies
Genetic: cytogenetic analysis
Correlative studies
Other: flow cytometry
Correlative studies
Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Genetic: polymorphism analysis
Correlative studies
Experimental: 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.

Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic transplantation
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: busulfan
Given IV or orally
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Procedure: peripheral blood stem cell transplantation
Undergo transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Genetic: polymorphism analysis
Correlative studies
Drug: tacrolimus
Given IV or orally
Other Names:
  • FK 506
  • Prograf
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

Detailed Description:

OBJECTIVES:

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.

  Eligibility

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

Inclusion Criteria:

  • Myelodysplastic syndrome (MDS) or transformed acute myelogenous leukemia (transformed from MDS)
  • 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:

  • HIV seropositivity
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322101

Locations
United States, Colorado
HealthOne Presbyterian St. Lukes Medical Center
Denver, Colorado, United States
United States, Georgia
Emory University
Altanta, Georgia, United States, 30322
United States, New York
Weill Cornell University
New York, New York, United States, 10021
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Veterans Administration Center-Seattle
Seattle, Washington, United States, 98108
United States, Wisconsin
Medical College Wisconsin
Milwaukee, Wisconsin, United States
Germany
Technical University Dresden
Dresden, Saxony, Germany, 01307
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Investigators
Principal Investigator: Bart Scott Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Bart Scott, Assistant Member, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00322101     History of Changes
Other Study ID Numbers: 1992.00, NCI-2010-00737, P01CA078902, K23HL084054, P01CA018029, P01HL036444
Study First Received: May 2, 2006
Results First Received: April 4, 2013
Last Updated: August 21, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Congenital Abnormalities
Neoplasms
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Down Syndrome
Leukemoid Reaction
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Chromosome Disorders
Genetic Diseases, Inborn
Leukocytosis
Leukocyte Disorders
Busulfan
Cyclophosphamide
Cyclosporins
Cyclosporine
Methotrexate
Mycophenolate mofetil

ClinicalTrials.gov processed this record on August 01, 2014