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

May 12, 2010 updated by: Fred Hutchinson Cancer Center

Conditioning For Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109-1024
        • Fred Hutchinson Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Incidence and severity of acute graft-versus-host disease (GVHD)
Incidence of donor engraftment

Secondary Outcome Measures

Outcome Measure
Relapse-free survival
Incidence of relapse
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 Epstein-Barr virus activation and post-transplantation lymphoproliferative disease

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Study Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

June 28, 2006

First Submitted That Met QC Criteria

June 28, 2006

First Posted (Estimate)

June 29, 2006

Study Record Updates

Last Update Posted (Estimate)

May 14, 2010

Last Update Submitted That Met QC Criteria

May 12, 2010

Last Verified

May 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2041.00
  • FHCRC-2041.00
  • GEMZYME-FHCRC-2041.00
  • CDR0000488969 (Registry Identifier: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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