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
  Purpose

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


Condition Intervention Phase
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
Drug: busulfan
Biological: anti-thymocyte globulin
Drug: tacrolimus
Drug: methotrexate
Procedure: peripheral blood stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Incidence and severity of acute GvHD [ Time Frame: Day 100 post-transplant ] [ Designated as safety issue: No ]
    Determined by LTFU.


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 23
Study Start Date: September 2004
Primary Completion Date: August 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01056614

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Investigators
Principal Investigator: Paul O'Donnell Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: O'Donnell, Paul, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT01056614     History of Changes
Other Study ID Numbers: 1913.00, NCI-2009-01785, P01HL036444
Study First Received: January 22, 2010
Last Updated: March 12, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cell Transformation, Neoplastic
Congenital Abnormalities
Blast Crisis
Neoplasms
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Neoplastic Processes
Bone Marrow Diseases
Hematologic Diseases
Pathologic Processes
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Methotrexate
Fludarabine monophosphate
Tacrolimus
Immunoglobulins
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on April 17, 2014