Busulfan and Fludarabine Before Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

October 1, 2012 updated by: University of California, San Francisco

Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing Matched Unrelated Donor Stem Cell Transplantation

RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more cancer cells are killed. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Tacrolimus and methotrexate may stop this from happening.

PURPOSE: This phase II trial is studying how well giving busulfan together with fludarabine before donor stem cell transplant works in treating patients with hematologic cancer.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the safety, in terms of treatment-related mortality at 100 days post-transplantation, of a myeloablative preparative regimen comprising busulfan and fludarabine and graft-vs-host disease (GVHD) prophylaxis comprising tacrolimus and methotrexate in patients with hematopoietic disorders undergoing matched unrelated donor stem cell transplantation.
  • Determine the efficacy, in terms of overall survival at 1-year post-transplantation, in patients treated with this regimen.

Secondary

  • Determine organ toxicity in patients treated with this regimen.
  • Determine neutrophil and platelet recovery in patients treated with this regimen.
  • Determine the incidence and severity of acute and chronic GVHD in patients treated with this regimen.

OUTLINE:

  • Myeloablative preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and fludarabine IV over 30 minutes on days -7 to -3.
  • Allogeneic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
  • Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously beginning on day -2 and continuing until discharged from the hospital (may convert to oral dosing administered twice daily when tolerated) and methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Study Type

Interventional

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
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer 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

16 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematopoietic disorders:

    • Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

      • Chronic phase disease failing imatinib mesylate therapy

        • Progressive disease OR failed to achieve a major cytogenetic response at 1 year after initiation of therapy

      • Accelerated phase disease, meeting 1 of the following criteria:

        • Failed to achieve complete cytogenetic remission at 1 year after initiation of therapy
        • Failed to achieve any cytogenetic response at 3 or 6 months during therapy
        • Progressive disease, demonstrated by worsening cytogenetic response in 2 consecutive analyses separated by 4 weeks
      • Blast crisis with < 10% blasts in bone marrow within 6 weeks of transplantation

    • Acute myeloid leukemia (AML), meeting 1 of the following criteria:

      • In second or greater remission
      • In first remission with poor prognosis cytogenetics [-5, -5q, -7, -7q and ≥ 2 cytogenetic abnormalities, t(6,9), t(9,11), or Philadelphia chromosome]
      • In hematologic remission but with persistent cytogenetic abnormalities
      • Primary refractory AML with < 10% blasts in bone marrow within 6 weeks of transplantation

    • Myelodysplasia with < 20% blasts in bone marrow within 6 weeks of transplantation and meeting 1 of the following criteria:

      • Advanced disease (International Prognostic Scoring System [IPSS] score intermediate-1, intermediate-2, or high risk)
      • Myelodysplastic syndromes (MDS) with progression to AML
      • Treatment-related AML

    • Acute lymphocytic leukemia (ALL), meeting 1 of the following criteria:

      • In second or greater remission
      • In first remission with high-risk cytogenetics [Philadelphia chromosome; t(4,11); and -7]
      • Primary refractory ALL with < 10% blasts in the bone marrow
    • Severe aplastic anemia that has failed immunosuppressive therapy

    • Non-Hodgkin's lymphoma, meeting 1 of the following criteria:

      • In second or greater remission
      • Relapsed disease in a patient not eligible for autologous stem cell transplantation

    • Lymphoproliferative disease (e.g., chronic lymphocytic leukemia or Waldenstrom's macroglobulinemia), meeting 1 of the following criteria:

      • In second or greater remission
      • Relapsed disease in a patient not eligible for autologous stem cell transplantation

    • Multiple myeloma, meeting 1 of the following criteria:

      • Stage II or III disease in first or greater relapse
      • Refractory disease
      • Newly diagnosed disease with chromosome 13 abnormalities

    • Advanced myeloproliferative disease, meeting 1 of the following criteria:

      • Myelofibrosis requiring > 2 units of packed red blood cells each month
      • Essential thrombocythemia or polycythemia rubra vera that has progressed to AML
      • Failed prior AML therapy
  • No active, uncontrolled CNS leukemia
  • Not eligible for autologous or mini-allogeneic transplantation
  • No fully matched or single-antigen mismatched sibling donor available

  • HLA-matched unrelated donor available

    • HLA typed at HLA-A, -B, -C, -DRB1 and/or -DQB1 by high-resolution techniques
    • For patients without HLA identical donors, mismatches at DQ (i.e., 8/8 match) and 1 additional mismatch at the allele level at HLA-A, -B, -C, or -DRB1 (i.e., 7/8 molecular match) allowed

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Creatinine < 2.0 mg/dL
  • Pulmonary diffusing capacity > 40% of predicted
  • Cardiac ejection fraction > 40% by MUGA or echocardiography
  • No active liver disease
  • Bilirubin ≤ 2.0 mg/dL
  • Alkaline phosphatase < 3 times upper limit of normal (ULN)
  • AST < 3 times ULN

  • Hepatitis C or active hepatitis B (HBV) allowed provided a liver biopsy is performed and ≤ grade 2 inflammation is present

    • Patients with active HBV viral replication must receive antiviral therapy
  • HIV negative
  • No ongoing active infection
  • Not pregnant or nursing
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 3 weeks since prior chemotherapy except for hydroxyurea or imatinib mesylate
  • More than 3 months since prior interferon

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
Treatment-related mortality in the first 100 days post-transplant
Overall survival at 1 year post-transplant

Secondary Outcome Measures

Outcome Measure
Incidence and severity of organ-specific toxicity
Engraftment including neutrophil and platelet recovery and donor chimerism at 3 and 12 months post-transplant
Rate of acute graft-vs-host disease (GVHD)
Rate of chronic GVHD

Collaborators and Investigators

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

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Thomas G. Martin, MD, University of California, San Francisco

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

January 1, 2002

Primary Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

March 9, 2006

First Submitted That Met QC Criteria

March 9, 2006

First Posted (Estimate)

March 13, 2006

Study Record Updates

Last Update Posted (Estimate)

October 2, 2012

Last Update Submitted That Met QC Criteria

October 1, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000463168
  • UCSF-02257
  • UCSF-2214
  • UCSF-H24045-22163-04

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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