Quimioterapia combinada con o sin trasplante autólogo de células madre en el tratamiento de pacientes con linfoma de células B del sistema nervioso central
31 de agosto de 2026 actualizado por: Alliance for Clinical Trials in Oncology
Un ensayo aleatorizado de fase II de quimioterapia de consolidación mieloablativa versus no mieloablativa para el linfoma primario de células B del SNC recién diagnosticado
The purpose of this study is to find out what effects (good and/or bad) treatment with chemotherapy and stem cell transplant compared with chemotherapy alone will have on primary CNS B-cell lymphoma. Currently the best treatment for patients with primary CNS B-cell lymphoma is not known.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
Primary Objective:
To compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of HDT/ASCT versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide
Secondary Objectives:
- To compare the two-year event-free survival (EFS) of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine
- To compare the overall survival (OS) of patients treated with the consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine
- To assess the toxicities associated with consolidation HDT/ASCT versus consolidation consisting of etoposide and cytarabine
- To determine diffusion MRI metrics (ADCmini, ADC25%, and ADCmean) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101)
- To determine brain FDG-PET metrics (tumor SUV and tumor versus background SUV) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101)
- To determine whether low baseline ADC measurements are associated with shorter PFS and OS (CALGB 581101)
- To determine whether reduction in tumor SUV by > 25% on brain FDG-PET/CT after one cycle of induction therapy is associated with improved PFS and OS (CALGB 581101)
- To determine which IHC-based biomarkers are predictive of an adverse prognosis (CALGB 151113)
- To determine which IHC-based biomarkers are predictive of a favorable prognosis (CALGB 151113) for BCL6 (B-cell CLL/lymphoma 6), and STAT 6 (signal transducer and activator of transcription 6, interleukin-4 induced)
- To analyze tumor tissue for gene expression profiles, and to correlate these profiles with treatment outcomes (CALGB 151113)
- To determine whether CSF proteome is a predictor of outcomes (prognostic marker) irrespective of treatment arm (CALGB 151113) for (IL-10 (interleukin 10) and C3 (complement component 3)
- To assess the neurocognitive function of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy (etoposide and cytarabine) as measured by serial administration of the International PCNSL Collaborative Group (IPCG) neurocognitive battery and evaluate the long-term survivorship differences between the two arms (CALGB 71105)
Tipo de estudio
Intervencionista
Inscripción (Actual)
113
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Alaska
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Anchorage, Alaska, Estados Unidos, 98508
- Anchorage Associates in Radiation Medicine
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Anchorage, Alaska, Estados Unidos, 99508
- Alaska Breast Care and Surgery LLC
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Anchorage, Alaska, Estados Unidos, 99508
- Alaska Oncology and Hematology LLC
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Anchorage, Alaska, Estados Unidos, 99508
- Alaska Women's Cancer Care
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Anchorage, Alaska, Estados Unidos, 99508
- Anchorage Oncology Centre
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Anchorage, Alaska, Estados Unidos, 99508
- Katmai Oncology Group
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Anchorage, Alaska, Estados Unidos, 99508
- Providence Alaska Medical Center
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Anchorage, Alaska, Estados Unidos, 99504
- Anchorage Radiation Therapy Center
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California
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Burbank, California, Estados Unidos, 91505
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
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La Jolla, California, Estados Unidos, 92093
- UC San Diego Moores Cancer Center
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Sacramento, California, Estados Unidos, 95817
- University of California Davis Comprehensive Cancer Center
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San Francisco, California, Estados Unidos, 94115
- UCSF Medical Center-Mount Zion
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San Francisco, California, Estados Unidos, 94143
- UCSF Medical Center-Parnassus
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06520
- Yale University
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Florida
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Tampa, Florida, Estados Unidos, 33612
- Moffitt Cancer Center
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory University/Winship Cancer Institute
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Idaho
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Boise, Idaho, Estados Unidos, 83712
- Saint Luke's Mountain States Tumor Institute
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Fruitland, Idaho, Estados Unidos, 83619
- Saint Luke's Mountain States Tumor Institute - Fruitland
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Meridian, Idaho, Estados Unidos, 83642
- Saint Luke's Mountain States Tumor Institute - Meridian
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Nampa, Idaho, Estados Unidos, 83686
- Saint Luke's Mountain States Tumor Institute - Nampa
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Twin Falls, Idaho, Estados Unidos, 83301
- Saint Luke's Mountain States Tumor Institute-Twin Falls
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Illinois
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Chicago, Illinois, Estados Unidos, 60637
- University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, Estados Unidos, 60612
- University of Illinois
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Indiana
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Richmond, Indiana, Estados Unidos, 47374
- Reid Health
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Kansas
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Kansas City, Kansas, Estados Unidos, 66160
- University of Kansas Cancer Center
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Kentucky
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Crestview Hills, Kentucky, Estados Unidos, 41017
- Oncology Hematology Care Inc-Crestview
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Louisiana
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New Orleans, Louisiana, Estados Unidos, 70112
- Tulane University Health Sciences Center
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Maryland
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Baltimore, Maryland, Estados Unidos, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Dana-Farber Cancer Institute
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Boston, Massachusetts, Estados Unidos, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital Cancer Center
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Michigan
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Battle Creek, Michigan, Estados Unidos, 49017
- Bronson Battle Creek
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Grand Rapids, Michigan, Estados Unidos, 49503
- Spectrum Health at Butterworth Campus
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Grand Rapids, Michigan, Estados Unidos, 49503
- Mercy Health Saint Mary's
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Kalamazoo, Michigan, Estados Unidos, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Estados Unidos, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Estados Unidos, 49001
- Borgess Medical Center
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Muskegon, Michigan, Estados Unidos, 49444
- Mercy Health Mercy Campus
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Niles, Michigan, Estados Unidos, 49120
- Lakeland Community Hospital
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Reed City, Michigan, Estados Unidos, 49677
- Spectrum Health Reed City Hospital
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Saint Joseph, Michigan, Estados Unidos, 49085
- Marie Yeager Cancer Center
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Saint Joseph, Michigan, Estados Unidos, 49085
- Lakeland Hospital
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Traverse City, Michigan, Estados Unidos, 49684
- Munson Medical Center
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Wyoming, Michigan, Estados Unidos, 49519
- Metro Health Hospital
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
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Missouri
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St Louis, Missouri, Estados Unidos, 63110
- Washington University School of Medicine
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68198
- University of Nebraska Medical Center
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New York
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New York, New York, Estados Unidos, 10065
- Weill Medical College of Cornell University
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Rochester, New York, Estados Unidos, 14642
- University of Rochester
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Stony Brook, New York, Estados Unidos, 11794
- Stony Brook University Medical Center
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Syracuse, New York, Estados Unidos, 13210
- State University of New York Upstate Medical University
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North Carolina
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Durham, North Carolina, Estados Unidos, 27710
- Duke University Medical Center
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Ohio
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Centerville, Ohio, Estados Unidos, 45459
- Dayton Physicians LLC-Miami Valley South
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Cincinnati, Ohio, Estados Unidos, 45242
- Oncology Hematology Care Inc-Blue Ash
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Cincinnati, Ohio, Estados Unidos, 45202
- Oncology Hematology Care Inc-Eden Park
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Cincinnati, Ohio, Estados Unidos, 45211
- Oncology Hematology Care Inc-Mercy West
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Cincinnati, Ohio, Estados Unidos, 45236
- Oncology Hematology Care Inc-Kenwood
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Cincinnati, Ohio, Estados Unidos, 45230
- Oncology Hematology Care Inc - Anderson
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Dayton, Ohio, Estados Unidos, 45406
- Good Samaritan Hospital - Dayton
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Dayton, Ohio, Estados Unidos, 45409
- Miami Valley Hospital
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Dayton, Ohio, Estados Unidos, 45415
- Dayton Physicians LLC-Samaritan North
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Dayton, Ohio, Estados Unidos, 45415
- Samaritan North Health Center
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Dayton, Ohio, Estados Unidos, 45420
- Dayton NCI Community Oncology Research Program
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Fairfield, Ohio, Estados Unidos, 45014
- Oncology Hematology Care Inc-Healthplex
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Findlay, Ohio, Estados Unidos, 45840
- Blanchard Valley Hospital
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Findlay, Ohio, Estados Unidos, 45840
- Armes Family Cancer Center
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Findlay, Ohio, Estados Unidos, 45840
- Orion Cancer Care
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Franklin, Ohio, Estados Unidos, 45005-1066
- Atrium Medical Center-Middletown Regional Hospital
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Franklin, Ohio, Estados Unidos, 45005
- Dayton Physicians LLC-Atrium
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Greenville, Ohio, Estados Unidos, 45331
- Wayne Hospital
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Greenville, Ohio, Estados Unidos, 45331
- Dayton Physicians LLC-Wayne
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Kettering, Ohio, Estados Unidos, 45429
- Kettering Medical Center
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Kettering, Ohio, Estados Unidos, 45409
- Greater Dayton Cancer Center
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Middletown, Ohio, Estados Unidos, 45042
- Dayton Physicians LLC-Signal Point
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Sidney, Ohio, Estados Unidos, 45365
- Dayton Physicians LLC-Wilson
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Springfield, Ohio, Estados Unidos, 45505
- Springfield Regional Medical Center
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Springfield, Ohio, Estados Unidos, 45504
- Springfield Regional Cancer Center
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Troy, Ohio, Estados Unidos, 45373
- Upper Valley Medical Center
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Troy, Ohio, Estados Unidos, 45373
- Dayton Physicians LLC-Upper Valley
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Oklahoma
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Tulsa, Oklahoma, Estados Unidos, 74136
- Surgical Associates Inc
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Tulsa, Oklahoma, Estados Unidos, 74146
- Warren Clinic Oncology-Tulsa
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Oregon
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Bend, Oregon, Estados Unidos, 97701
- Saint Charles Health System
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Clackamas, Oregon, Estados Unidos, 97015
- Clackamas Radiation Oncology Center
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Clackamas, Oregon, Estados Unidos, 97015
- Providence Oncology and Hematology Care Southeast
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Coos Bay, Oregon, Estados Unidos, 97420
- Bay Area Hospital
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Milwaukie, Oregon, Estados Unidos, 97222
- Providence Milwaukie Hospital
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Newberg, Oregon, Estados Unidos, 97132
- Providence Newberg Medical Center
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Oregon City, Oregon, Estados Unidos, 97045
- Providence Willamette Falls Medical Center
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Portland, Oregon, Estados Unidos, 97213
- Providence Portland Medical Center
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Portland, Oregon, Estados Unidos, 97225
- Providence Saint Vincent Medical Center
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Pennsylvania
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Danville, Pennsylvania, Estados Unidos, 17822
- Geisinger Medical Center
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Lewistown, Pennsylvania, Estados Unidos, 17044
- Lewistown Hospital
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Pittsburgh, Pennsylvania, Estados Unidos, 15232
- University of Pittsburgh Cancer Institute (UPCI)
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Utah
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Salt Lake City, Utah, Estados Unidos, 84112
- Huntsman Cancer Institute/University of Utah
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Vermont
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Berlin Corners, Vermont, Estados Unidos, 05602
- Central Vermont Medical Center/National Life Cancer Treatment
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Burlington, Vermont, Estados Unidos, 05401
- University of Vermont Medical Center
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Burlington, Vermont, Estados Unidos, 05405
- University of Vermont College of Medicine
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Virginia
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Richmond, Virginia, Estados Unidos, 23298
- Virginia Commonwealth University/Massey Cancer Center
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Washington
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Aberdeen, Washington, Estados Unidos, 98520
- Providence Regional Cancer System-Aberdeen
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Anacortes, Washington, Estados Unidos, 98221
- Cancer Care Center at Island Hospital
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Bellevue, Washington, Estados Unidos, 98005
- Swedish Cancer Institute-Eastside Oncology Hematology
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Bellingham, Washington, Estados Unidos, 98225
- PeaceHealth Saint Joseph Medical Center
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Centralia, Washington, Estados Unidos, 98531
- Providence Regional Cancer System-Centralia
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Edmonds, Washington, Estados Unidos, 98026
- Swedish Medical Center-Edmonds
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Everett, Washington, Estados Unidos, 98201
- Providence Regional Cancer Partnership
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Issaquah, Washington, Estados Unidos, 98029
- Swedish Cancer Institute-Issaquah
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Lacey, Washington, Estados Unidos, 98503
- Providence Regional Cancer System-Lacey
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Longview, Washington, Estados Unidos, 98632
- PeaceHealth Saint John Medical Center
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Seattle, Washington, Estados Unidos, 98109
- Fred Hutchinson Cancer Research Center
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Seattle, Washington, Estados Unidos, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, Estados Unidos, 98195
- University of Washington Medical Center
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Seattle, Washington, Estados Unidos, 98107
- Swedish Medical Center-Ballard Campus
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Seattle, Washington, Estados Unidos, 98104
- Minor and James Medical PLLC
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Seattle, Washington, Estados Unidos, 98104
- Pacific Gynecology Specialists
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Seattle, Washington, Estados Unidos, 98112
- Group Health Cooperative-Seattle
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Seattle, Washington, Estados Unidos, 98122-4307
- Swedish Medical Center-First Hill
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Shelton, Washington, Estados Unidos, 98584
- Providence Regional Cancer System-Shelton
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Spokane, Washington, Estados Unidos, 99204
- Rockwood Cancer Treatment Center-DHEC-Downtown
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Spokane Valley, Washington, Estados Unidos, 99216
- Rockwood Clinic Cancer Treatment Center-Valley
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Vancouver, Washington, Estados Unidos, 98664
- PeaceHealth Southwest Medical Center
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Vancouver, Washington, Estados Unidos, 98684
- Compass Oncology Vancouver
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Walla Walla, Washington, Estados Unidos, 99362
- Providence Saint Mary Regional Cancer Center
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Yakima, Washington, Estados Unidos, 98902
- North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
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Yelm, Washington, Estados Unidos, 98597
- Providence Regional Cancer System-Yelm
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Wisconsin
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La Crosse, Wisconsin, Estados Unidos, 54601
- Mayo Clinic Health System-Franciscan Healthcare
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Madison, Wisconsin, Estados Unidos, 53792
- University of Wisconsin Hospital and Clinics
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 75 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
- Documentation of Disease: Diagnosis of primary CNS diffuse large B-cell lymphoma confirmed by one of the following: brain biopsy or resection, cerebrospinal fluid and vitreous fluid.
- Other Lymphomas: Patients must have no evidence or history of non-Hodgkin lymphoma (NHL) outside of CNS.
- Previous Treatment: Patients must have no prior chemotherapy or radiation therapy for lymphoma.
- Age- Patients must be between the ages of 18 and 75 years.
- Karnofsky Performance Scale - Patients must measure Karnofsky Performance Scale ≥ 30 (≥ 50 for patients ages 60-70).
- Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing; women of childbearing potential must have a negative serum or urine pregnancy test 10-14 days prior to registration; in addition, women and men of childbearing potential must commit to use an effective form of contraception throughout their participation in this study; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)
- HIV - Patients must have negative HIV serology.
- Hepatitis - Patients must have negative HCV serology (unless HBsAb positive patient has recently received HBV vaccine, in this case HBcAb should be negative). All patients must be screened for hepatitis B infection before starting treatment. Those patients who test positive for hepatitis B should be closely monitored for evidence of active HBV infection and hepatitis during and for several months after rituximab treatment. PCNSL patients with a history of hepatitis B infection should be treated with entecavir or lamivudine (physician discretion for choice of drug) as antiviral prophylaxis to prevent hepatitis B reactivation.
- Organ Transplant or Immunosuppressant Therapy - Patient must have no history of organ transplantation or ongoing immunosuppressant therapy.
- Required Initial Laboratory Values: ANC ≥ 1500/mcL, AST and ALT < 2 x upper limit of normal (ULN), total bilirubin ≤ 3 mg/dL, creatinine clearance ≥ 50 mL/min, platelet count ≥ 100,000/mcL
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Otro: Arm I
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant. |
Given IV Given IV |
|
Otro: Arm II
Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy. |
Given IV Given IV |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Progression Free Survival
Periodo de tiempo: 2 years
|
The primary endpoint is to compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of HDT/ASCT versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide. PFS time = time from Registration to earliest date of Progression or Death due to any cause, censoring non-progressed and alive patients at the date of last disease status evaluation. Response will be defined using the modified IPCG criteria. Progressive disease is defined as > 25% increase in contrast-enhancing CNS (brain and spine if latter abnormal at baseline) disease, appearance of any new, measurable (>/= 10mm) contrast-enhancing disease or recurrent or new ocular or CSF disease. |
2 years
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Event Free Survival
Periodo de tiempo: 2 years
|
To compare the two-year event-free survival (EFS) of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine. EFS event = same definition as PFS with non-protocol treatment also considered an event |
2 years
|
|
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Periodo de tiempo: 7 years
|
Number of patients reporting at least one adverse event at least possibly related to treatment. |
7 years
|
|
Overall Survival
Periodo de tiempo: 2 years
|
To compare the overall survival (OS) of patients treated with the consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine. OS event = Registration/Randomization to Death due to any cause |
2 years
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Colaboradores
Investigadores
- Silla de estudio: Tracy Batchelor, MD, MPH, Massachusetts General Hospital
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de septiembre de 2012
Finalización primaria (Actual)
14 de enero de 2021
Finalización del estudio (Actual)
24 de febrero de 2022
Fechas de registro del estudio
Enviado por primera vez
13 de enero de 2012
Primero enviado que cumplió con los criterios de control de calidad
13 de enero de 2012
Publicado por primera vez (Estimado)
18 de enero de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
24 de septiembre de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
31 de agosto de 2026
Última verificación
1 de agosto de 2026
Más información
Términos relacionados con este estudio
Palabras clave
- Linfoma difuso de células grandes en adultos en estadio III
- Linfoma difuso de células grandes en adultos en estadio IV
- Linfoma no Hodgkin primario del sistema nervioso central
- Linfoma difuso de células grandes en adultos no contiguos en estadio II
- Linfoma difuso de células grandes en adultos contiguos en estadio II
- Linfoma difuso de células grandes en adultos en estadio I
Términos MeSH relevantes adicionales
- Neoplasias
- Enfermedades del sistema inmunológico
- Neoplasias por tipo histológico
- Enfermedades linfáticas
- Trastornos linfoproliferativos
- Trastornos inmunoproliferativos
- Linfoma No Hodgkin
- Linfoma de células B
- Enfermedades hemic y linfáticas
- Linfoma
- Linfoma de células B grandes, difuso
- Péptidos
- Aminoácidos, péptidos y proteínas
- Proteínas
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Terapéutica
- Procedimientos quirúrgicos, operativo
- Ácidos nucleicos, nucleótidos y nucleósidos
- Hidrocarburos
- Hidrocarburos, cíclico
- Factores biológicos
- Carbohidratos
- Podoflotoxina
- Tetrahidronaftalenos
- Naftalenos
- Hidrocarburos aromáticos policíclicos
- Hidrocarburos, aromáticos
- Compuestos policíclicos
- Glucósidos
- Glucósidos
- Trasplante
- Amidas
- Citidina
- Nucleósidos de pirimidina
- Pirimidinas
- Fosforamidas
- Compuestos organofosforados
- Nucleósidos
- Péptidos de señalización intercelular y proteínas
- Arabinonucleósidos
- Glicoproteínas
- Glucoconjugados
- Trasplante de células
- Terapia basada en células y tejidos
- Terapia biológica
- Trietilenefosforamida
- Aziridinas
- Azirines
- Factores estimulantes de colonias
- Factores de crecimiento de células hematopoyéticas
- Citocinas
- Compuestos de nitrosourea
- Urea
- Compuestos nitrosos
- Citarabina
- Carmustina
- Etopósido
- Tiotepa
- Trasplante de células madre
- Factor estimulador de colonias de granulocitos
Otros números de identificación del estudio
- CALGB-51101
- CDR0000721927 (Identificador de registro: NCI Physician Data Query)
- NCI-2012-00110 (Identificador de registro: NCI Clinical Trial Reporting Program)
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .