Combination Chemotherapy With or Without Autologous Stem Cell Transplant in Treating Patients With Central Nervous System B-Cell Lymphoma

A Randomized Phase II Trial of Myeloablative Versus Non-Myeloablative Consolidation Chemotherapy for Newly Diagnosed Primary CNS B-cell Lymphoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: carmustine; Drug: etoposide; Drug: cytarabine; Drug: thiotepa; Drug: G-CSF; Procedure: stem cell transplant

Detailed Description

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:

1. 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
2. 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
3. To assess the toxicities associated with consolidation HDT/ASCT versus consolidation consisting of etoposide and cytarabine
4. 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)
5. 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)
6. To determine whether low baseline ADC measurements are associated with shorter PFS and OS (CALGB 581101)
7. 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)
8. To determine which IHC-based biomarkers are predictive of an adverse prognosis (CALGB 151113)
9. 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)
10. To analyze tumor tissue for gene expression profiles, and to correlate these profiles with treatment outcomes (CALGB 151113)
11. 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)
12. 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)

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 98508
      • Anchorage Associates in Radiation Medicine
    • Anchorage, Alaska, United States, 99508
      • Alaska Breast Care and Surgery LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
    • Anchorage, Alaska, United States, 99508
      • Anchorage Oncology Centre
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
    • Anchorage, Alaska, United States, 99504
      • Anchorage Radiation Therapy Center
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • San Francisco, California, United States, 94143
      • UCSF Medical Center-Parnassus
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University/Winship Cancer Institute
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Mountain States Tumor Institute
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Mountain States Tumor Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Mountain States Tumor Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Mountain States Tumor Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Indiana
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • Oncology Hematology Care Inc-Crestview
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Niles, Michigan, United States, 49120
      • Lakeland Community Hospital
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Medical College of Cornell University
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Dayton Physicians LLC-Miami Valley South
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc-Blue Ash
    • Cincinnati, Ohio, United States, 45202
      • Oncology Hematology Care Inc-Eden Park
    • Cincinnati, Ohio, United States, 45211
      • Oncology Hematology Care Inc-Mercy West
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Inc-Kenwood
    • Cincinnati, Ohio, United States, 45230
      • Oncology Hematology Care Inc - Anderson
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Dayton Physicians LLC-Samaritan North
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45420
      • Dayton NCI Community Oncology Research Program
    • Fairfield, Ohio, United States, 45014
      • Oncology Hematology Care Inc-Healthplex
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Findlay, Ohio, United States, 45840
      • Armes Family Cancer Center
    • Findlay, Ohio, United States, 45840
      • Orion Cancer Care
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Franklin, Ohio, United States, 45005
      • Dayton Physicians LLC-Atrium
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Greenville, Ohio, United States, 45331
      • Dayton Physicians LLC-Wayne
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Kettering, Ohio, United States, 45409
      • Greater Dayton Cancer Center
    • Middletown, Ohio, United States, 45042
      • Dayton Physicians LLC-Signal Point
    • Sidney, Ohio, United States, 45365
      • Dayton Physicians LLC-Wilson
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Cancer Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Troy, Ohio, United States, 45373
      • Dayton Physicians LLC-Upper Valley
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Surgical Associates Inc
    • Tulsa, Oklahoma, United States, 74146
      • Warren Clinic Oncology-Tulsa
  • Oregon
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Oncology and Hematology Care Southeast
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Lewistown, Pennsylvania, United States, 17044
      • Lewistown Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Vermont
    • Berlin Corners, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellevue, Washington, United States, 98005
      • Swedish Cancer Institute-Eastside Oncology Hematology
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Medical Center-Edmonds
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Spokane, Washington, United States, 99204
      • Rockwood Cancer Treatment Center-DHEC-Downtown
    • Spokane Valley, Washington, United States, 99216
      • Rockwood Clinic Cancer Treatment Center-Valley
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Vancouver, Washington, United States, 98684
      • Compass Oncology Vancouver
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System-Franciscan Healthcare
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

1. 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.
2. Other Lymphomas: Patients must have no evidence or history of non-Hodgkin lymphoma (NHL) outside of CNS.
3. Previous Treatment: Patients must have no prior chemotherapy or radiation therapy for lymphoma.
4. Age- Patients must be between the ages of 18 and 75 years.
5. Karnofsky Performance Scale - Patients must measure Karnofsky Performance Scale ≥ 30 (≥ 50 for patients ages 60-70).
6. 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)
7. HIV - Patients must have negative HIV serology.
8. 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.
9. Organ Transplant or Immunosuppressant Therapy - Patient must have no history of organ transplantation or ongoing immunosuppressant therapy.
10. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Arm I; Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.	Drug: carmustine; Given IV; Drug: thiotepa; Given IV; Drug: G-CSF; Procedure: stem cell transplant
Other: Arm II; Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy.	Drug: etoposide; Given IV; Drug: cytarabine; Given IV; Drug: G-CSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival	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	Number of patients reporting at least one adverse event at least possibly related to treatment.	7 years
Overall Survival	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

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Tracy Batchelor, MD, MPH, Massachusetts General Hospital

Publications and helpful links

General Publications

• Batchelor TT, Giri S, Ruppert AS, Geyer SM, Smith SE, Mohile N, Swinnen LJ, Friedberg JW, Kahl BS, Bartlett NL, Hsi ED, Cheson BD, Wagner-Johnston N, Nayak L, Leonard JP, Rubenstein JL. Myeloablative vs nonmyeloablative consolidation for primary central nervous system lymphoma: results of Alliance 51101. Blood Adv. 2024 Jun 25;8(12):3189-3199. doi: 10.1182/bloodadvances.2023011657.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): December 10, 2020
• Study Completion (Estimated): May 2, 2027

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 13, 2012
• First Posted (Estimated): January 18, 2012

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; primary central nervous system non-Hodgkin lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Hemic and Lymphatic Diseases; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Surgical Procedures, Operative; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Biological Factors; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Transplantation; Amides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Phosphoramides; Organophosphorus Compounds; Nucleosides; Intercellular Signaling Peptides and Proteins; Arabinonucleosides; Glycoproteins; Glycoconjugates; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Triethylenephosphoramide; Aziridines; Azirines; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Nitrosourea Compounds; Urea; Nitroso Compounds; Cytarabine; Carmustine; Etoposide; Thiotepa; Stem Cell Transplantation; Granulocyte Colony-Stimulating Factor
• Other Study ID Numbers: CALGB-51101; CDR0000721927 (Registry Identifier: NCI Physician Data Query); NCI-2012-00110 (Registry Identifier: NCI Clinical Trial Reporting Program)