Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing Matched Unrelated Donor Stem Cell Transplantation
16 Years
60 Years
Both
Anemia, Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
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 Center | San Francisco, California 94115 |
