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Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00045435
First received: September 6, 2002
Last updated: January 29, 2014
Last verified: January 2014

September 6, 2002
January 29, 2014
April 2002
June 2009   (final data collection date for primary outcome measure)
  • Disease-free survival-incidence of survival without relapse [ Time Frame: By 1 year after transplant ] [ Designated as safety issue: No ]
    Sufficient evidence will be taken to be an observed rate of DFS at one year after transplant that corresponds to a one-sided 95% confidence interval with an upper limit lower than 35%.
  • Nonrelapse mortality (NRM)-incidence of nonrelapse death [ Time Frame: By day 200 after transplant ] [ Designated as safety issue: No ]
    Defined as death without morphologic evidence of disease. Sufficient evidence will be taken to be an observed rate of NRM within 200 days of transplant that corresponds to a one-sided 80% confidence interval with a lower limit greater than 15%.
  • NRM-incidence of nonrelapse death [ Time Frame: By 1 year after transplant ] [ Designated as safety issue: No ]
    Defined as death without morphologic evidence of disease. Sufficient evidence will be taken to be an observed rate of NRM within 200 days of transplant that corresponds to a one-sided 80% confidence interval with a lower limit greater than 15%.
Not Provided
Complete list of historical versions of study NCT00045435 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: By 1 year after transplant ] [ Designated as safety issue: No ]
  • Incidence of relapse [ Time Frame: By 1 year after transplant ] [ Designated as safety issue: No ]
  • Incidence of rejection [ Time Frame: By 1 year after transplant ] [ Designated as safety issue: No ]
  • Incidence of acute and chronic graft-vs-host disease (GVHD) [ Time Frame: Day 80 (patients who taper off CSP by day 56) ] [ Designated as safety issue: No ]
  • Incidence of acute and chronic GVHD [ Time Frame: Day 100 (patients who taper off CSP by day 77) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission
Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation From HLA Matched Related Donors for Treatment of Older Patients With De Novo or Secondary Acute Myeloid Leukemia in First Complete Remission

This phase II trial studies how well reduced intensity donor peripheral blood stem cell (PBSC) transplant works in treating patients with de novo or secondary acute myeloid leukemia (AML) in remission. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening

PRIMARY OBJECTIVES:

I. To determine if a one-year disease free survival of >= 35% can be achieved among patients >= 55 years old with de novo and secondary AML in first complete remission (CR1) who undergo nonmyeloablative hematopoietic stem cell transplant (HSCT) from human leukocyte antigen (HLA) identical related donors.

II. To determine if a day +200 nonrelapse related mortality of < 15% can be achieved among patients >= 55 years old with de novo and secondary AML in CR1 who undergo nonmyeloablative HSCT from HLA identical related donors.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.

TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine (CSP) orally (PO) twice daily (BID) on days -3 to 56 with taper to day 77. Patients also receive mycophenolate mofetil (MMF) PO BID on days 0-27.

After completion of study treatment, patients are followed up on days 28, 56, and 84; months 6, 12, 18, and 24; and then yearly for 5 years.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • Adult Acute Monoblastic Leukemia (M5a)
  • Adult Acute Monocytic Leukemia (M5b)
  • Adult Acute Myeloblastic Leukemia With Maturation (M2)
  • Adult Acute Myeloblastic Leukemia Without Maturation (M1)
  • 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(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • Adult Acute Myelomonocytic Leukemia (M4)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Secondary Acute Myeloid Leukemia
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
    Undergo nonmyeloablative allogeneic PBSC transplant
  • Drug: fludarabine phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • Beneflur
    • Fludara
  • Radiation: total-body irradiation
    Undergo TBI
    Other Name: TBI
  • Drug: cyclosporine
    Given PO
    Other Names:
    • ciclosporin
    • cyclosporin
    • cyclosporin A
    • CYSP
    • Sandimmune
  • Drug: mycophenolate mofetil
    Given PO
    Other Names:
    • Cellcept
    • MMF
  • Procedure: peripheral blood stem cell transplantation
    Undergo nonmyeloablative allogeneic PBSC transplant
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
Experimental: Treatment (nonmyeloablative donor PBSC transplant)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0.

TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.

Interventions:
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  • Drug: fludarabine phosphate
  • Radiation: total-body irradiation
  • Drug: cyclosporine
  • Drug: mycophenolate mofetil
  • Procedure: peripheral blood stem cell transplantation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
Not Provided
June 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with de novo AML (French-American-British [FAB] MO-M2, M4-M7) or secondary AML who achieve CR1 after induction chemotherapy and one or two cycles of consolidation chemotherapy
  • Transplant conditioning must occur within 6 months of diagnosis
  • Patient enrollment must be approved by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI) or the PI's designee
  • DONOR: Related donor who is genotypically or phenotypically identical
  • DONOR: Age >= 12 years
  • DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
  • DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Exclusion Criteria:

  • AML FAB M3
  • AML involvement of the central nervous system (CNS) as defined by a positive cytospin of cerebral spinal fluid at the time of enrollment
  • Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology
  • Human immunodeficiency virus (HIV) seropositivity
  • Fungal infections with radiographic progression after receipt of amphotericin B or active triazole for greater than one month
  • Diffusion capacity of carbon monoxide (DLCO) corrected < 40%
  • Total lung capacity (TLC) < 40%
  • Forced expiratory volume in one second (FEV1) < 40% or requiring supplementary oxygen
  • The FHCRC principal investigator of the study must approve enrollment of all patients with pulmonary nodules
  • Cardiac ejection fraction < 40%
  • Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced 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 > 3mg/dL, or symptomatic biliary disease
  • Karnofsky Performance Score < 70
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Females who are pregnant or breastfeeding
  • No intensive chemotherapy can be given within three weeks (or the interval in which a cycle of standard chemotherapy would be administered in a non-transplant setting) prior to initiating the nonmyeloablative transplant conditioning
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
  • Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
  • Patients with active bacterial or fungal infections unresponsive to medical therapy
  • DONOR: Identical twin
  • DONOR: Pregnancy
  • DONOR: HIV seropositivity
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness
Both
55 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00045435
1654.00, NCI-2011-01307
Yes
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Brenda Sandmaier Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP