Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01056614
First received: January 22, 2010
Last updated: May 27, 2014
Last verified: May 2014

January 22, 2010
May 27, 2014
September 2004
August 2005   (final data collection date for primary outcome measure)
Incidence of acute GvHD [ Time Frame: Day 100 post-transplant ] [ Designated as safety issue: No ]
Maximum grade of acute GVHD and the number of therapies required to treat GVHD will be determined.
Incidence and severity of acute GvHD [ Time Frame: Day 100 post-transplant ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01056614 on ClinicalTrials.gov Archive Site
  • Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy [ Time Frame: At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3 ] [ Designated as safety issue: No ]
  • Thymoglobulin pharmacokinetics [ Time Frame: On day -3 prior to the first dose, on day -1 one hour after completion of infusion and on day 1 at 0900 ] [ Designated as safety issue: No ]
  • Incidence of donor cell engraftment [ Time Frame: By day 100 ] [ Designated as safety issue: No ]
  • Incidence of system toxicities >= grade 3 as graded per CTCAE v.3 [ Time Frame: Up to day 100 after transplantation ] [ Designated as safety issue: Yes ]
  • Incidence of chronic GvHD [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Incidence of non-relapse mortality defined as death without history of post-transplant relapse [ Time Frame: At day 100 ] [ Designated as safety issue: No ]
  • Incidence of non-relapse mortality defined as death without history of post-transplant relapse [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • Incidence of relapse [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
    Defined by either morphological or cytogenetic evidence of chronic myelogenous leukemia (CML), AML, MDS or other myeloproliferative disease in marrow, blood, or other sites, or laboratory evidence of residual disease.
  • Relapse-free survival [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • Incidence of EBV activation defined as an increase in plasma EBV DNA to >= 1000 copies/mL as determined by quantitative polymerase chain reaction (PCR) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy [ Designated as safety issue: No ]
  • Thymoglobulin pharmacokinetics [ Designated as safety issue: No ]
  • Incidence of donor cell engraftment [ Designated as safety issue: No ]
  • System toxicities as assessed by >= Grade 3 per CTCAE v.3 [ Designated as safety issue: Yes ]
  • Incidence and severity of chronic GvHD [ Designated as safety issue: No ]
  • Incidence of non-relapse mortality [ Time Frame: At day 100 and at 1 year ] [ Designated as safety issue: No ]
  • Incidence of relapse [ Designated as safety issue: No ]
  • Relapse-free survival [ Designated as safety issue: No ]
  • Incidence of EBV activation [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies
Conditioning for Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

PRIMARY OBJECTIVE:

I. Determine the incidence and severity of acute graft-versus-host disease (GvHD).

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose variability and evaluation of a limited sampling strategy.

II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics.

III. Determine the incidence of donor engraftment.

IV. Determine system toxicities >= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3.

V. Determine the incidence and severity of chronic GvHD.

VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr).

VII. Determine the incidence of relapse.

VIII. Determine relapse-free survival.

IX. Determine the incidence of Epstein-Barr virus (EBV) activation.

OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed at 1 year.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Accelerated Phase Chronic Myelogenous Leukemia
  • 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)
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Myelodysplastic Syndromes
  • Chronic Phase Chronic Myelogenous Leukemia
  • de Novo Myelodysplastic Syndromes
  • Hematopoietic/Lymphoid Cancer
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Drug: fludarabine phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • Beneflur
    • Fludara
  • Drug: busulfan
    Given IV
    Other Names:
    • BSF
    • BU
    • Misulfan
    • Mitosan
    • Myeloleukon
  • Biological: anti-thymocyte globulin
    Given IV
    Other Names:
    • ATG
    • ATGAM
    • lymphocyte immune globulin
    • Thymoglobulin
  • Drug: tacrolimus
    Given IV and orally
    Other Names:
    • FK 506
    • Prograf
  • Drug: methotrexate
    Given IV
    Other Names:
    • amethopterin
    • Folex
    • methylaminopterin
    • Mexate
    • MTX
  • Procedure: peripheral blood stem cell transplantation
    Undergo allogeneic PBSC transplant
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Undergo allogeneic PBSC transplant
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (chemotherapy, PBSC transplant)
Patients receive fludarabine phosphate IV over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic PBSC transplant on day 0. Patients then receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.
Interventions:
  • Drug: fludarabine phosphate
  • Drug: busulfan
  • Biological: anti-thymocyte globulin
  • Drug: tacrolimus
  • Drug: methotrexate
  • Procedure: peripheral blood stem cell transplantation
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Other: laboratory biomarker analysis
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
23
Not Provided
August 2005   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Chronic myelogenous leukemia in chronic phase, accelerated phase and treated blast phase (CP2)
  • Acute myeloid leukemia (AML) in remission or early relapse (< 10% marrow blasts)
  • Myelodysplastic syndromes (MDS) ( all risk groups)
  • Other myeloproliferative disorders
  • DONOR: related or unrelated donors matched for human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele
  • DONOR: donor must consent to peripheral blood stem cell (PBSC) mobilization with granulocyte colony-stimulating factor (G-CSF) and leukapheresis; related donors will be collected at Fred Hutchinson Cancer Research Center (FHCRC), while unrelated donors will be collected through the National Marrow Donor Program (NMDP) or other donor centers
  • DONOR: Age 12-75 yrs

Exclusion Criteria:

  • Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
  • Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal
  • Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted
  • Impaired renal function (creatinine > 2 times normal or estimated creatinine clearance < 60 ml/min)

    • MALE: ([140 -age in years] x ideal body weight [kg])/72 x serum creatinine (SCr) (mg/dL)
    • FEMALE: .85 x ([140-age in years] x ideal body weight [kg])/72 x SCr (mg/dL)
  • Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or acceleration of HIV replication
  • Female patients who are pregnant or breast feeding
  • Life expectancy severely limited by diseases other than malignancy
  • DONOR: donors who for any reason are unable to tolerate the mobilization and leukapheresis procedure
  • DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive
  • DONOR: female donors who have a positive pregnancy test
Both
up to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01056614
1913.00, NCI-2009-01785, 1913.00, P30CA015704, P01HL036444
Yes
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Cancer Institute (NCI)
Principal Investigator: H. Joachim Deeg Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
May 2014

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