NCT00301912

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2002

Completed
4.2 years until next milestone

First Submitted

Initial submission to the registry

March 9, 2006

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 13, 2006

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2007

Completed
Last Updated

October 2, 2012

Status Verified

October 1, 2012

Enrollment Period

5.8 years

First QC Date

March 9, 2006

Last Update Submit

October 1, 2012

Conditions

AnemiaChronic Myeloproliferative DisordersLeukemiaLymphomaMultiple Myeloma and Plasma Cell NeoplasmMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative Diseases

Keywords

chronic phase chronic myelogenous leukemiaaccelerated phase chronic myelogenous leukemiablastic phase chronic myelogenous leukemiaadult acute myeloid leukemia in remissionadult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult 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 leukemiasecondary acute myeloid leukemiade novo myelodysplastic syndromespreviously treated myelodysplastic syndromessecondary myelodysplastic syndromesatypical chronic myeloid leukemiamyelodysplastic/myeloproliferative disease, unclassifiableadult acute lymphoblastic leukemia in remissionrecurrent adult lymphoblastic lymphomaanemiarefractory chronic lymphocytic leukemiastage III chronic lymphocytic leukemiastage IV chronic lymphocytic leukemiaWaldenstrom macroglobulinemiastage II multiple myelomastage III multiple myelomarefractory multiple myelomapolycythemia veraessential thrombocythemiaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomarecurrent adult Burkitt lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomarelapsing chronic myelogenous leukemiachronic eosinophilic leukemiachronic idiopathic myelofibrosischronic myelomonocytic leukemiachronic neutrophilic leukemianoncontiguous stage II adult Burkitt lymphomanoncontiguous stage II adult diffuse large cell lymphomanoncontiguous stage II adult diffuse mixed cell lymphomanoncontiguous stage II adult diffuse small cleaved cell lymphomanoncontiguous stage II adult immunoblastic large cell lymphomanoncontiguous stage II adult lymphoblastic lymphomanoncontiguous stage II grade 1 follicular lymphomanoncontiguous stage II grade 2 follicular lymphomanoncontiguous stage II grade 3 follicular lymphomanoncontiguous stage II mantle cell lymphomanoncontiguous stage II marginal zone lymphomanoncontiguous stage II small lymphocytic lymphomastage III adult Burkitt lymphomastage III adult diffuse large cell lymphomastage III adult diffuse mixed cell lymphomastage III adult diffuse small cleaved cell lymphomastage III adult immunoblastic large cell lymphomastage III adult lymphoblastic lymphomastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage III mantle cell lymphomastage III marginal zone lymphomastage III small lymphocytic lymphomastage IV adult Burkitt lymphomastage IV adult diffuse large cell lymphomastage IV adult diffuse mixed cell lymphomastage IV adult diffuse small cleaved cell lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV mantle cell lymphomastage IV marginal zone lymphomastage IV small lymphocytic lymphomarecurrent adult acute lymphoblastic leukemiastage I multiple myelomachildhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (2)

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

  • Overall survival at 1 year post-transplant

Secondary Outcomes (4)

  • 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

Interventions

filgrastimBIOLOGICAL
busulfanDRUG
fludarabine phosphateDRUG
methotrexateDRUG
tacrolimusDRUG
allogeneic bone marrow transplantationPROCEDURE
allogeneic hematopoietic stem cell transplantationPROCEDURE
peripheral blood stem cell transplantationPROCEDURE

Eligibility Criteria

Age16 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

AnemiaMyeloproliferative DisordersLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesMyelodysplastic-Myeloproliferative DiseasesLeukemia, Myeloid, Chronic-PhaseLeukemia, Myeloid, Accelerated PhaseBlast CrisisCongenital AbnormalitiesLeukemia, Myeloid, AcuteLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativePrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom MacroglobulinemiaPolycythemia VeraThrombocythemia, EssentialLymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLymphoma, FollicularLymphoma, Mantle-CellPdgfra-Associated Chronic Eosinophilic LeukemiaPrimary MyelofibrosisLeukemia, Myelomonocytic, ChronicLeukemia, Neutrophilic, Chronic

Interventions

FilgrastimBusulfanfludarabine phosphateMethotrexateTacrolimusPeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Hematologic DiseasesHemic and Lymphatic DiseasesBone Marrow DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, LymphoidLeukemia, B-CellBone Marrow NeoplasmsHematologic NeoplasmsNeoplasms by SiteBlood Coagulation DisordersThrombocytosisBlood Platelet DisordersLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus Infections

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating FactorColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsButylene GlycolsGlycolsAlcoholsOrganic ChemicalsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsMacrolidesLactonesHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Study Officials

  • Thomas G. Martin, MD

    University of California, San Francisco

    STUDY CHAIR
0

Study Design

Study Type
interventional
Phase
phase 2
Masking
NONE
Purpose
TREATMENT
Sponsor Type
OTHER

Study Record Dates

First Submitted

March 9, 2006

First Posted

March 13, 2006

Study Start

January 1, 2002

Primary Completion

November 1, 2007

Last Updated

October 2, 2012

Record last verified: 2012-10

Locations

US(1)