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

This study has been withdrawn prior to enrollment.
(Withdrawn because study never opened to accrual)
National Cancer Institute (NCI)
Information provided by:
University of California, San Francisco
ClinicalTrials.gov Identifier:
First received: March 9, 2006
Last updated: October 1, 2012
Last verified: October 2012

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.

Condition Intervention Phase
Chronic Myeloproliferative Disorders
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: filgrastim
Drug: busulfan
Drug: fludarabine phosphate
Drug: methotrexate
Drug: tacrolimus
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing Matched Unrelated Donor Stem Cell Transplantation

Resource links provided by NLM:

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Treatment-related mortality in the first 100 days post-transplant [ Designated as safety issue: No ]
  • Overall survival at 1 year post-transplant [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and severity of organ-specific toxicity [ Designated as safety issue: Yes ]
  • Engraftment including neutrophil and platelet recovery and donor chimerism at 3 and 12 months post-transplant [ Designated as safety issue: No ]
  • Rate of acute graft-vs-host disease (GVHD) [ Designated as safety issue: No ]
  • Rate of chronic GVHD [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2002
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Detailed Description:



  • 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.


  • 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.


  • 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.


Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • See Disease Characteristics
  • More than 3 weeks since prior chemotherapy except for hydroxyurea or imatinib mesylate
  • More than 3 months since prior interferon
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00301912

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
National Cancer Institute (NCI)
Study Chair: Thomas G. Martin, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: Thomas G. Martin, III, UCSF Helen Diller Family Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00301912     History of Changes
Other Study ID Numbers: CDR0000463168  UCSF-02257  UCSF-2214  UCSF-H24045-22163-04 
Study First Received: March 9, 2006
Last Updated: October 1, 2012
Health Authority: United States: Federal Government

Keywords provided by University of California, San Francisco:
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
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)
recurrent adult acute myeloid leukemia
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
adult acute lymphoblastic leukemia in remission
recurrent adult lymphoblastic lymphoma
refractory chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Waldenstrom macroglobulinemia
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
polycythemia vera
essential thrombocythemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma

Additional relevant MeSH terms:
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms, Plasma Cell
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Precancerous Conditions
Vascular Diseases
Fludarabine phosphate
Alkylating Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2016