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


Phase 2
16 Years
60 Years
Not Enrolling
Both
Anemia, Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment-related mortality in the first 100 days post-transplant

Safety Issue:

No

Principal Investigator

Thomas G. Martin, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco

Authority:

United States: Federal Government

Study ID:

CDR0000463168

NCT ID:

NCT00301912

Start Date:

January 2002

Completion Date:

Related Keywords:

  • Anemia
  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • 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
  • anemia
  • 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
  • splenic marginal zone lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • relapsing chronic myelogenous leukemia
  • chronic eosinophilic leukemia
  • chronic idiopathic myelofibrosis
  • chronic myelomonocytic leukemia
  • chronic neutrophilic leukemia
  • noncontiguous stage II adult Burkitt lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • stage III adult Burkitt lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage III marginal zone lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent adult acute lymphoblastic leukemia
  • stage I multiple myeloma
  • childhood myelodysplastic syndromes
  • Anemia
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115