Clinical trial NCT01511562: Combination Chemotherapy With or Without Autologous Stem Cell Transplant in Treating Patients With Central Nervous System B-Cell Lymphoma
Official title: A Randomized Phase II Trial of Myeloablative Versus Non-Myeloablative Consolidation Chemotherapy for Newly Diagnosed Primary CNS B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma
Keywords: primary central nervous system non-Hodgkin lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-01-18
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: progression free survival
timeFrame: Up to 10 years
Secondary outcomes:
measure: event free survival
timeFrame: Up to 10 years
measure: number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to 10 years
measure: overall survival
timeFrame: Up to 10 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Anchorage Associates in Radiation Medicine
state: Alaska
city: Anchorage
country: United States
facility: Anchorage Radiation Therapy Center
state: Alaska
city: Anchorage
country: United States
facility: Alaska Breast Care and Surgery LLC
state: Alaska
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology LLC
state: Alaska
city: Anchorage
country: United States
facility: Alaska Women's Cancer Care
state: Alaska
city: Anchorage
country: United States
facility: Anchorage Oncology Centre
state: Alaska
city: Anchorage
country: United States
facility: Katmai Oncology Group
state: Alaska
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center/Disney Family Cancer Center
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Parnassus
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Boise
country: United States
facility: Saint Luke's Mountain States Tumor Institute
state: Idaho
city: Fruitland
country: United States
facility: Saint Luke's Mountain States Tumor Institute - Fruitland
state: Idaho
city: Meridian
country: United States
facility: Saint Luke's Mountain States Tumor Institute - Meridian
state: Idaho
city: Nampa
country: United States
facility: Saint Luke's Mountain States Tumor Institute - Nampa
state: Idaho
city: Twin Falls
country: United States
facility: Saint Luke's Mountain States Tumor Institute-Twin Falls
state: Idaho
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Richmond
country: United States
facility: Reid Health
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Crestview Hills
country: United States
facility: Oncology Hematology Care Inc-Crestview
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Battle Creek
country: United States
facility: Bronson Battle Creek
state: Michigan
city: Grand Rapids
country: United States
facility: Mercy Health Saint Mary's
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Muskegon
country: United States
facility: Mercy Health Mercy Campus
state: Michigan
city: Niles
country: United States
facility: Lakeland Community Hospital
state: Michigan
city: Reed City
country: United States
facility: Spectrum Health Reed City Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Marie Yeager Cancer Center
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Centerville
country: United States
facility: Dayton Physicians LLC-Miami Valley South
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc-Eden Park
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc-Mercy West
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc - Anderson
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc-Kenwood
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc-Blue Ash
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital - Dayton
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Physicians LLC-Samaritan North
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Health Center
state: Ohio
city: Dayton
country: United States
facility: Dayton NCI Community Oncology Research Program
state: Ohio
city: Fairfield
country: United States
facility: Oncology Hematology Care Inc-Healthplex
state: Ohio
city: Findlay
country: United States
facility: Armes Family Cancer Center
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Hospital
state: Ohio
city: Findlay
country: United States
facility: Orion Cancer Care
state: Ohio
city: Franklin
country: United States
facility: Atrium Medical Center-Middletown Regional Hospital
state: Ohio
city: Franklin
country: United States
facility: Dayton Physicians LLC-Atrium
state: Ohio
city: Greenville
country: United States
facility: Dayton Physicians LLC-Wayne
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Middletown
country: United States
facility: Dayton Physicians LLC-Signal Point
state: Ohio
city: Sidney
country: United States
facility: Dayton Physicians LLC-Wilson
state: Ohio
city: Springfield
country: United States
facility: Springfield Regional Cancer Center
state: Ohio
city: Springfield
country: United States
facility: Springfield Regional Medical Center
state: Ohio
city: Troy
country: United States
facility: Dayton Physicians LLC-Upper Valley
state: Ohio
city: Troy
country: United States
facility: Upper Valley Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Surgical Associates Inc
state: Oklahoma
city: Tulsa
country: United States
facility: Warren Clinic Oncology-Tulsa
state: Oklahoma
city: Bend
country: United States
facility: Saint Charles Health System
state: Oregon
city: Clackamas
country: United States
facility: Clackamas Radiation Oncology Center
state: Oregon
city: Clackamas
country: United States
facility: Providence Oncology and Hematology Care Southeast
state: Oregon
city: Coos Bay
country: United States
facility: Bay Area Hospital
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Newberg
country: United States
facility: Providence Newberg Medical Center
state: Oregon
city: Oregon City
country: United States
facility: Providence Willamette Falls Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Lewistown
country: United States
facility: Lewistown Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute (UPCI)
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute/University of Utah
state: Utah
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Aberdeen
country: United States
facility: Providence Regional Cancer System-Aberdeen
state: Washington
city: Anacortes
country: United States
facility: Cancer Care Center at Island Hospital
state: Washington
city: Bellevue
country: United States
facility: Swedish Cancer Institute-Eastside Oncology Hematology
state: Washington
city: Bellingham
country: United States
facility: PeaceHealth Saint Joseph Medical Center
state: Washington
city: Centralia
country: United States
facility: Providence Regional Cancer System-Centralia
state: Washington
city: Edmonds
country: United States
facility: Swedish Medical Center-Edmonds
state: Washington
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute-Issaquah
state: Washington
city: Lacey
country: United States
facility: Providence Regional Cancer System-Lacey
state: Washington
city: Longview
country: United States
facility: PeaceHealth Saint John Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical PLLC
state: Washington
city: Seattle
country: United States
facility: Pacific Gynecology Specialists
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-Ballard Campus
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: Group Health Cooperative-Seattle
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center-First Hill
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Shelton
country: United States
facility: Providence Regional Cancer System-Shelton
state: Washington
city: Spokane Valley
country: United States
facility: Rockwood Clinic Cancer Treatment Center-Valley
state: Washington
city: Spokane
country: United States
facility: Rockwood Cancer Treatment Center-DHEC-Downtown
state: Washington
city: Vancouver
country: United States
facility: PeaceHealth Southwest Medical Center
state: Washington
city: Vancouver
country: United States
facility: Compass Oncology Vancouver
state: Washington
city: Walla Walla
country: United States
facility: Providence Saint Mary Regional Cancer Center
state: Washington
city: Yakima
country: United States
facility: North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
state: Washington
city: Yelm
country: United States
facility: Providence Regional Cancer System-Yelm
state: Washington
city: La Crosse
country: United States
facility: Mayo Clinic Health System-Franciscan Healthcare
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: Massachusetts General Hospital
name: Tracy Batchelor, MD, MPH
role: STUDY_CHAIR
References: