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Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission

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ClinicalTrials.gov Identifier: NCT00070135
Recruitment Status : Completed
First Posted : October 7, 2003
Results First Posted : April 28, 2017
Last Update Posted : June 12, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

October 3, 2003
October 7, 2003
March 20, 2017
April 28, 2017
June 12, 2018
January 2004
December 2013   (Final data collection date for primary outcome measure)
2 Year Disease Free Survival In Unrelated Donor Recipient Group [ Time Frame: 2 years ]
Percentage of participants who were alive and relapse free at 2 years for patients who were matched with an unrelated donor for transplant. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method. A relapse is defined as any of the following:
  • Reappearance of leukemia blasts cells in peripheral blood
  • >5% blasts in the marrow, not attributable to another cause (e.g., bone marrow regeneration)
  • If there are no circulating blasts, but the marrow contains 5-20% blasts, a repeat bone marrow ≥ 1 week later with >5% blasts is necessary to meet the criteria for relapse
  • The development of extramedullary leukemia or leukemic cells in the cerebral spinal fluid
Not Provided
Complete list of historical versions of study NCT00070135 on ClinicalTrials.gov Archive Site
  • 2 Year DFS for All Patients [ Time Frame: Up to 2 years ]
    Percentage of participants who were alive and relapse free at 2 years for all patients. The 2 year disease free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
  • Non-relapse Mortality (NRM) [ Time Frame: Up to 5 years ]
    Percentage of patients who died due to causes other than relapse
Not Provided
Not Provided
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Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission
A Phase II Study Of Allogeneic Transplant For Older Patients With AML In First Morphologic Complete Remission Using A Non-Myeloablative Preparative Regimen
This phase II trial studies how well fludarabine and busulfan followed by a donor (allogeneic) stem cell transplant work in treating older patients with acute myeloid leukemia that is in first complete remission. Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stops 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. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus, methotrexate, and rabbit antithymocyte globulin before or after the transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. Determine if allogeneic transplantation from a matched sibling or unrelated donor using a non-myeloablative preparative regimen results in a 2-year disease-free survival (DFS) that is better than historical results using standard chemotherapy.

SECONDARY OBJECTIVES:

I. Determine 2-year actuarial risks of transplant-related mortality, acute and chronic graft-versus-host (GVHD) disease and relapse among patients with acute myeloid leukemia (AML) in first complete remission (CR1) following a non-myeloablative preparative regimen.

II. To examine recovery of T and B cell number and function following non-myeloablative stem cell transplant.

III. To examine the time course of T, B and myeloid progenitor chimerism following this preparative regimen.

IV. To characterize the pharmacokinetics of intravenous busulfan used in a non-myeloablative preparation regimen in AML patients age >= 60 years.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine intravenously (IV) over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV twice daily (BID) on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2.

ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRASNPLANTATION (PBSC): Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim subcutaneously (SC) daily beginning on day 12 and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then every 6 months for 3 years.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Adult Acute Myeloid Leukemia in Remission
  • Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
  • Biological: filgrastim
    Given SC
  • Biological: Anti-Thymocyte Globulin
    Given IV
  • Drug: busulfan
    Given IV
  • Drug: fludarabine phosphate
    Given IV
  • Drug: methotrexate
    Given IV
  • Drug: tacrolimus
    Given PO or IV
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic PBSC transplantation
    Other Name: HSC, HSCT
Experimental: Treatment (fludarabine, busulfan, allogeneic PBSC)

PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.

GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2.

ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover.

Interventions:
  • Biological: filgrastim
  • Biological: Anti-Thymocyte Globulin
  • Drug: busulfan
  • Drug: fludarabine phosphate
  • Drug: methotrexate
  • Drug: tacrolimus
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. doi: 10.1200/JCO.2015.62.7273. Epub 2015 Nov 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
121
Not Provided
June 15, 2016
December 2013   (Final data collection date for primary outcome measure)

Eligibility Criteria:

  • Patients with acute myeloid leukemia (AML) (excluding French-American-British [FAB] classification system M3) who have achieved a first morphologic complete remission and who meet the criteria below; patients with preceding myelodysplastic syndrome (MDS) or treatment-related AML are eligible; patients with prior central nervous system (CNS) involvement are eligible as long as disease is in remission at transplant; patients with acute leukemia following blast transformation of prior chronic myeloid leukemia (CML) or other myeloproliferative disease are excluded
  • Complete remission (CR) will be defined according to the revised recommendations of the International Working Group (24) as all of the following:

    • Normal bone marrow morphology with < 5% blasts
    • Absolute neutrophil count (ANC) > 1,000/uL, referring to the count needed to confirm that the patient achieved a CR
    • Platelet count > 100,000/uL
    • No extramedullary leukemia
    • No blasts in peripheral blood
  • CR was achieved after one or two (but no more than two) cycles of induction chemotherapy with standard cytotoxic chemotherapy (e.g., cytarabine and an anthracycline) or after no more than four cycles of a hypomethylating agent containing regimen including either 5-azacytidine or decitabine
  • Patients may have received as many as but no more than two cycles of consolidation therapy prior to transplant; any consolidation regimen that does not require transplant can be used; no more than 6 months can elapse from documentation of morphologic CR to transplant; the platelet count does not need to be > 100,000/uL after consolidation, as long as the bone marrow assessment prior to transplant does not show relapse
  • Identification of hematopoietic cell donor
  • >= 4 weeks since prior chemotherapy, radiation therapy, and surgery
  • Performance status 0-2
  • Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease
  • Left ventricular ejection fraction (LVEF) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) >= 30%
  • No uncontrolled diabetes mellitus or active serious infection requiring antibiotics
  • No known hypersensitivity to E. coli-derived products
  • No human immunodeficiency virus (HIV) infection
  • Calculated creatinine clearance >= 40 cc/min
  • Bilirubin < 2 mg/dL

    * If bilirubin is 2-3 mg/dL, but direct bilirubin is normal then patient will be considered eligible

  • Aspartate aminotransferase (AST) < 3 x upper limit of normal
  • DONOR: HLA-identical sibling (6/6); the donor must be determined to be an human leukocyte antigen (HLA)-identical sibling (6/6) by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1)
  • DONOR: Matched unrelated donor (10/10); high resolution molecular typing at the following loci is required: HLA-A, -B, -C, -DRB1, and -DQB1
  • DONOR: the donor must be healthy and must be an acceptable donor as per institutional standards for stem cell donation
  • DONOR: the donor must have no significant cardiopulmonary, renal, endocrine, or hepatic disease
  • DONOR: there is no donor age restriction if the donor is a matched sibling
  • DONOR: syngeneic donors are not eligible
Sexes Eligible for Study: All
60 Years to 74 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00070135
CALGB-100103
CDR0000330001 ( Registry Identifier: NCI Physician Data Query )
NCI-2009-00438 ( Registry Identifier: NCI Clinical Trial Reporting Program )
U10CA180821 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Steven M. Devine, MD Ohio State University Comprehensive Cancer Center
Alliance for Clinical Trials in Oncology
May 2018

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