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Fludarabine and Busulfan Followed by Donor Peripheral Stem Cell Transplant and Antithymocyte Globulin, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00346359
First Posted: June 29, 2006
Last Update Posted: May 14, 2010
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center
  Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of abnormal and cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal or 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 antithymocyte globulin, tacrolimus, and methotrexate before or after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine together with busulfan followed by donor peripheral stem cell transplant and antithymocyte globulin, tacrolimus, and methotrexate works in treating patients with myeloid cancer.


Condition Intervention Phase
Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Biological: anti-thymocyte globulin Drug: busulfan Drug: fludarabine phosphate Drug: methotrexate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Phase 2

Study Type: Interventional
Study Design: Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Conditioning For Hematopoietic 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 graft-versus-host disease (GVHD)
  • Incidence of donor engraftment

Secondary Outcome Measures:
  • Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy
  • Pharmacokinetics of antithymocyte globulin
  • Pharmacokinetics of fludarabine phosphate and its effect on lymphocytes
  • Incidence of specific toxic effects ≥ grade 3
  • Incidence and severity of chronic GVHD
  • Incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation
  • Incidence of relapse
  • Relapse-free survival
  • Incidence of Epstein-Barr virus activation and post-transplantation lymphoproliferative disease

Estimated Enrollment: 40
Study Start Date: March 2006
Study Completion Date: November 2007
Detailed Description:

OBJECTIVES:

Primary

  • Determine the incidence and severity of acute graft-versus-host disease (GVHD) in patients with myeloid malignancies treated with conditioning regimen comprising fludarabine phosphate and busulfan followed by allogeneic peripheral blood stem cell transplantation and GVHD prophylaxis comprising antithymocyte globulin, tacrolimus, and methotrexate.
  • Determine the incidence of donor engraftment in patients treated with this regimen.

Secondary

  • Determine the pharmacokinetics of IV busulfan, including interdose variability and evaluation of a limited sampling strategy, in these patients.
  • Determine the pharmacokinetics of antithymocyte globulin in these patients.
  • Determine the pharmacokinetics of fludarabine phosphate and its effect on lymphocytes in these patients.
  • Determine the incidence of specific toxic effects ≥ grade 3 in patients treated with this regimen.
  • Determine the incidence and severity of chronic GVHD in these patients.
  • Determine the incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation in these patients.
  • Determine the incidence of relapse in these patients.
  • Determine relapse-free survival of these patients.
  • Determine the incidence of Epstein-Barr virus activation in these patients.

OUTLINE:

  • Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and busulfan IV over 3 hours on days -5 to -2. Prior to the conditioning regimen, patients whose cerebrospinal fluid is positive for malignant cells receive intrathecal methotrexate or cranial irradiation for CNS prophylaxis.
  • Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive filgrastim (G-CSF)-mobilized allogeneic PBSCs IV on day 0.
  • Graft-versus-host disease prophylaxis: Patients receive antithymocyte globulin IV over at least 10 hours on days -3 to -1. They also receive tacrolimus orally twice daily or IV continuously beginning on day -1 and continuing until up to day 55, followed by a taper until day 180 in the absence of graft-versus-host disease. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following myeloid malignancies:

    • Chronic myelogenous leukemia meeting 1 of the following criteria:

      • Chronic phase
      • Accelerated phase
      • Treated blast phase
    • Acute myeloid leukemia meeting 1 of the following criteria:

      • In remission
      • In early relapse, defined as < 10% marrow blasts
    • Myelodysplastic syndromes, including all risk groups
    • Other myeloproliferative disorders
  • HLA-A, -B, -C, -DRB1, and -DQB1 matched related or unrelated donor available

PATIENT CHARACTERISTICS:

  • No other disease that would severely limit life expectancy
  • AST ≤ 2 times normal
  • Creatinine ≤ 2 times normal OR creatinine clearance ≥ 60 mL/min
  • No cardiac insufficiency requiring treatment
  • No symptomatic coronary artery disease
  • PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR PO _2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted
  • HIV negative
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No post-transplantation growth factor during methotrexate administration
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00346359


Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Study Chair: Paul V. O'Donnell, MD, PhD Fred Hutchinson Cancer Research Center
  More Information

ClinicalTrials.gov Identifier: NCT00346359     History of Changes
Other Study ID Numbers: 2041.00
FHCRC-2041.00
GEMZYME-FHCRC-2041.00
CDR0000488969 ( Registry Identifier: PDQ )
First Submitted: June 28, 2006
First Posted: June 29, 2006
Last Update Posted: May 14, 2010
Last Verified: May 2010

Keywords provided by Fred Hutchinson Cancer Research Center:
graft versus host disease
chronic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
atypical chronic myeloid leukemia
chronic myelomonocytic leukemia
juvenile myelomonocytic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
secondary acute myeloid leukemia
chronic eosinophilic leukemia
chronic idiopathic myelofibrosis
chronic neutrophilic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
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)
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Graft vs Host Disease
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immune System Diseases
Methotrexate
Fludarabine phosphate
Tacrolimus
Busulfan
Antilymphocyte Serum
Vidarabine
Fludarabine
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents