NCT00448201

Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as busulfan and fludarabine, before a donor stem cell transplant helps stop the growth of cancer and abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Immunosuppressive therapy may improve bone marrow function and may be an effective treatment for hematologic cancer or other disease. PURPOSE: This clinical trial is studying the side effects and how well giving busulfan and fludarabine with or without antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer or other disease.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
71

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2011

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 14, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 16, 2007

Completed
3.8 years until next milestone

Study Start

First participant enrolled

January 7, 2011

Completed
4 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 11, 2011

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 23, 2012

Completed
5 years until next milestone

Results Posted

Study results publicly available

May 30, 2017

Completed
Last Updated

May 30, 2017

Status Verified

May 1, 2017

Enrollment Period

4 days

First QC Date

March 14, 2007

Results QC Date

April 17, 2017

Last Update Submit

May 23, 2017

Conditions

Keywords

adult 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)prolymphocytic leukemiaaccelerated phase chronic myelogenous leukemiaadult acute lymphoblastic leukemia in remissionadult acute myeloid leukemia in remissionblastic phase chronic myelogenous leukemiachildhood acute lymphoblastic leukemia in remissionchildhood acute myeloid leukemia in remissionchildhood chronic myelogenous leukemiachronic phase chronic myelogenous leukemiade novo myelodysplastic syndromesextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomanoncontiguous 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 lymphomapreviously treated myelodysplastic syndromesrecurrent adult acute lymphoblastic leukemiarecurrent adult Burkitt lymphomarecurrent adult Hodgkin lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult acute myeloid leukemiarecurrent childhood acute myeloid leukemiarecurrent/refractory childhood Hodgkin lymphomarecurrent childhood acute lymphoblastic leukemiarecurrent childhood large cell lymphomarecurrent childhood lymphoblastic lymphomarecurrent childhood small noncleaved cell lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent mycosis fungoides/Sezary syndromerecurrent small lymphocytic lymphomarefractory chronic lymphocytic leukemiarefractory multiple myelomarelapsing chronic myelogenous leukemiasecondary acute myeloid leukemiasecondary myelodysplastic syndromessplenic marginal zone lymphomastage I multiple myelomastage II multiple myelomastage III adult Burkitt lymphomastage III adult Hodgkin 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 chronic lymphocytic leukemiastage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage III mantle cell lymphomastage III marginal zone lymphomastage III multiple myelomastage III small lymphocytic lymphomastage IV adult Burkitt lymphomastage IV adult Hodgkin 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 chronic lymphocytic leukemiastage 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 lymphomaprimary myelofibrosisWaldenstrom macroglobulinemiaadult nasal type extranodal natural killer (NK)/T-cell lymphomarecurrent adult grade III lymphomatoid granulomatosischildhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

  • Treatment-related Mortality

    Treatment related mortality for first 6 months. Defined as the number of treatment related deaths excluding deaths due to disease relapse.

    6 months

Secondary Outcomes (4)

  • Complete Response at 6 and 12 Months Post-transplant

    6 and 12 months

  • Complete or Mixed Donor Chimerism at 30, 60, and 90 Days Post-transplant

    Days 30, 60, and 90

  • 5-year Disease-free Survival

    Year 5

  • Graft-vs-host Disease at 6 Months Post-transplant

    6 Months

Study Arms (4)

Methotrexate Only Arm

ACTIVE COMPARATOR

GVHD Prophylaxis with Methotrexate

Biological: sargramostimBiological: therapeutic allogeneic lymphocytesDrug: busulfanDrug: fludarabine phosphateDrug: methotrexateDrug: tacrolimusProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantation

2 Doses ATG + Methotrexate

ACTIVE COMPARATOR

GVHD prophylaxis with antithymocyte globulin (ATG) + Methotrexate

Biological: anti-thymocyte globulinBiological: sargramostimBiological: therapeutic allogeneic lymphocytesDrug: busulfanDrug: fludarabine phosphateDrug: methotrexateDrug: tacrolimusProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantation

2 Doses ATG

ACTIVE COMPARATOR

GVHD prophylaxis with 2 doses ATG

Biological: anti-thymocyte globulinBiological: sargramostimBiological: therapeutic allogeneic lymphocytesDrug: busulfanDrug: fludarabine phosphateDrug: tacrolimusProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantation

3 Doses ATG

ACTIVE COMPARATOR

GVHD prophylaxis with 3 doses ATG

Biological: anti-thymocyte globulinBiological: sargramostimBiological: therapeutic allogeneic lymphocytesDrug: busulfanDrug: fludarabine phosphateDrug: tacrolimusProcedure: nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure: peripheral blood stem cell transplantation

Interventions

0.5 mg/kg on day -3, 2.5 mg/kg on day -2 (groups 2, 3 and 4) and 3 mg/kg on day -1 (group 4 only)

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATG
sargramostimBIOLOGICAL

GM-CSF 500 ug everyday (QD) subcutaneously will be given to recipients who remain with an Absolute neutrophil count (ANC) \< 1000/microliter (uL) past day 20

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATGMethotrexate Only Arm

A minimum total cluster of differentiation 34 (CD34)+ cell dose of 3 x 10\^6 cells/kg and a maximum 8 x 10\^6 cells/kg will be infused on day 0

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATGMethotrexate Only Arm

6.4 mg/kg by continuous IV infusion over 48 hours on Days -6 and -5

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATGMethotrexate Only Arm

fludarabine 30 mg/m\^2/day x 5 days IV piggyback (IVPB) over 30 minutes on Days -7 through -3

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATGMethotrexate Only Arm

Methotrexate 5 mg/m\^2 per day on days +1, +3 and +6

2 Doses ATG + MethotrexateMethotrexate Only Arm

Suggested starting dose is 0.03 mg/kg po bid starting on Day -1

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATGMethotrexate Only Arm

Minimum total CD34+ cells of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on Day 0

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATGMethotrexate Only Arm

Minimum total CD34+ cells of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on Day 0

2 Doses ATG2 Doses ATG + Methotrexate3 Doses ATGMethotrexate Only Arm

Eligibility Criteria

Age10 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * Chronic lymphocytic leukemia (CLL), meeting the following criteria: * Absolute lymphocyte count \> 5,000/mm³ * Lymphocytes must appear morphologically mature with \< 55% prolymphocytes * Lymphocyte phenotype with expression of CD19 and cluster of differentiation 5 (CD5) * Prolymphocytic leukemia (PLL), meeting the following criteria: * Absolute lymphocyte count \> 5,000/mm³ * More than 55% prolymphocytes * Morphologically diagnosed * Chronic myelogenous leukemia (CML), meeting the following criteria: * Diagnosis of CML or similar myeloproliferative disorders based on t(9;22) or related t(9;12) cytogenetic abnormalities AND characterized by elevated white blood cell (WBC) counts in peripheral blood or bone marrow * In first chronic phase CML and a candidate for treatment with reduced-dose busulfan * Patients with other cytogenetic abnormalities, such as t(9;12), that are associated with an aggressive clinical course are eligible * Non-Hodgkin's lymphoma (NHL), meeting the following criteria: * Any World Health Organization (WHO) class histologic subtype allowed * Core biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping * Bone marrow biopsies as sole means of diagnosis are not allowed for follicular lymphoma * Hodgkin's lymphoma, meeting the following criteria: * Any WHO class histologic subtype allowed * Core biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping * Multiple myeloma, meeting the following criteria: * Active disease requiring treatment (Durie-Salmon stages I, II, or III) * Acute myeloid leukemia with documented control, defined as \< 10% bone marrow blasts and no circulating blasts * Acute lymphoblastic leukemia, meeting the following criteria: * In early first relapse or beyond OR in first complete remission and has 1 of the following high-risk features: * t(9;22) or t(4;11) * WBC count \> 30,000/mm³ at presentation * Non-T-cell phenotype * More than 30 years of age * Agnogenic myeloid metaplasia/myelofibrosis * Patients who are transfusion dependent or who have evolving myelodysplastic or leukemic features or high-risk cytogenetic abnormalities are eligible * Myelodysplastic syndromes (MDS) as defined by WHO criteria * Meets 1 of the following criteria: * Over 55 years of age * Ineligible for busulfan-based therapy based on diminished organ function or poor performance status * Indolent and chemotherapy-responsive CLL, low-grade NHL, small lymphocytic lymphoma, or PLL * Patients who have undergone prior autologous stem cell transplantation are preferentially enrolled on clinical trial CALGB-100002, if available and patient is eligible * HLA-matched or mismatched related donor or HLA-matched unrelated donor available * HLA-identical sibling (6/6 or 9/10) (minimal serologic typing required for class I \[A, B\]; molecular typing required for class II (DRB1)) * 9/10 matched unrelated donor (MUD) (molecular analysis at HLA A, B, C, DRB1, and DQB1 by high resolution typing required) * 5/6 MUD (molecular analysis at HLA A, B, and DRB1 required) * No syngeneic donors PATIENT CHARACTERISTICS: * Creatinine clearance ≥ 40 mL/min * Bilirubin ≤ 3 times upper limit of normal (ULN) * aspartate aminotransferase (AST) ≤ 3 times ULN * Diffusing capacity of the lungs for carbon monoxide (DLCO) \> 40% with no symptomatic pulmonary disease * Left ventricular ejection fraction (LVEF) ≥ 30% by multigated acquisition scan (MUGA) * No uncontrolled diabetes mellitus or active serious infection * No known hypersensitivity to Escherichia coli-derived products * No HIV infection * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 4 weeks since prior chemotherapy, radiotherapy (except prophylactic cranial x-ray therapy), or surgery

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

Sponsors & Collaborators

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Related Links

MeSH Terms

Conditions

Myeloproliferative DisordersLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellMyelodysplastic SyndromesCongenital AbnormalitiesLeukemia, ProlymphocyticLeukemia, Myeloid, Accelerated PhaseBlast CrisisLeukemia, Myeloid, Chronic-PhaseLymphoma, B-Cell, Marginal ZonePrecursor Cell Lymphoblastic Leukemia-LymphomaBurkitt LymphomaHodgkin DiseaseLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLeukemia, Myeloid, AcuteRecurrenceDendritic Cell Sarcoma, InterdigitatingLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellPrimary MyelofibrosisWaldenstrom MacroglobulinemiaLymphoma, Extranodal NK-T-Cell

Interventions

Antilymphocyte SerumsargramostimBusulfanfludarabine phosphateMethotrexateTacrolimusPeripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, LymphoidLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsHistiocytic Disorders, MalignantHistiocytosisLymphoma, T-CellLeukemia, B-Cell

Intervention Hierarchy (Ancestors)

Immune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesButylene 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

Limitations and Caveats

Per the protocol, non-serious adverse events were not captured as this was a high-dose transplant study and grades 1,2, and 3 adverse events were expected. No unexpected toxicities were seen beyond those reported in the Serious Adverse Event section.

Results Point of Contact

Title
Dr. Thomas Shea
Organization
UNC Lineberger Comprehensive Cancer Center

Study Officials

  • Thomas C. Shea, MD

    UNC Lineberger Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2007

First Posted

March 16, 2007

Study Start

January 7, 2011

Primary Completion

January 11, 2011

Study Completion

May 23, 2012

Last Updated

May 30, 2017

Results First Posted

May 30, 2017

Record last verified: 2017-05

Locations