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:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01056614
First received: January 22, 2010
Last updated: March 12, 2014
Last verified: March 2014

January 22, 2010
March 12, 2014
September 2004
August 2005   (final data collection date for primary outcome measure)
Incidence and severity of acute GvHD [ Time Frame: Day 100 post-transplant ] [ Designated as safety issue: No ]
Determined by LTFU.
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 ] [ 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 ]
  • System toxicities as assessed by >= Grade 3 per CTCAE v.3 [ Time Frame: Evaluated up to the time the patient is discharged from medical care at the SCCA ] [ Designated as safety issue: Yes ]
  • Incidence and severity of chronic GvHD [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Incidence of non-relapse mortality [ Time Frame: At day 100 and 1 year ] [ Designated as safety issue: No ]
  • Incidence of relapse [ Time Frame: At 1 year ] [ Designated as safety issue: No ]
  • Relapse-free survival [ Time Frame: At one year ] [ Designated as safety issue: No ]
  • Incidence of EBV activation [ Time Frame: Every Monday and Thursday of each week ] [ 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 Stem Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

RATIONALE: 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.

PURPOSE: 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

PRIMARY OBJECTIVE:

I. Determine the incidence and severity of acute GvHD.

SECONDARY OBJECTIVES:

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

II. Determine thymoglobulin pharmacokinetics. III. Determine the incidence of donor engraftment. IV. Determine system toxicities >= Grade 3 per CTCAE 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 yr. VII. Determine the incidence of relapse. VIII. Determine relapse-free survival. IX. Determine the incidence of EBV activation.

OUTLINE:

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 donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV continuously or orally 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
    Given IV
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Procedure: allogeneic hematopoietic stem cell transplantation
    Given IV
Experimental: Arm I
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 donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV continuously or orally 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
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:

  • Myelodysplastic syndromes (MDS) ( all risk groups)
  • 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)
  • Other myeloproliferative disorders
  • Related or unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 defined by high resolution DNA typing or mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele
  • Age 12-75 years (donor)

Exclusion Criteria:

  • Life expectancy severely limited by diseases other than malignancy
  • Hepatic disease, with AST > 2 times normal
  • Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
  • Severe hypoxemia , pO2 < 70 mm Hg, with decreased 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)
  • HIV-positive patients due to risk of reactivation or acceleration of HIV replication
  • Female patients who are pregnant or breast feeding due to risks to fetus from conditioning regimen and potential risks to nursing infants
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, P01HL036444
Yes
O'Donnell, Paul, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • National Cancer Institute (NCI)
  • National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Paul O'Donnell Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
March 2014

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