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

Sponsor

University of California, San Francisco (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00301912

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Anemia Chronic Myeloproliferative Disorders Leukemia Lymphoma 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

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Masking:

None (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

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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