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

NCT ID: NCT00301912

Last Updated: 2012-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2002-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Anemia Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases

Keywords

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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

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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filgrastim

Intervention Type BIOLOGICAL

busulfan

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

methotrexate

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

16 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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UCSF Helen Diller Family Comprehensive Cancer Center

Principal Investigators

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Thomas G. Martin, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

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UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Countries

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United States

Other Identifiers

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UCSF-02257

Identifier Type: -

Identifier Source: secondary_id

UCSF-2214

Identifier Type: -

Identifier Source: secondary_id

UCSF-H24045-22163-04

Identifier Type: -

Identifier Source: secondary_id

CDR0000463168

Identifier Type: -

Identifier Source: org_study_id