Early or Delayed Fludarabine and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia
Leukemia
About this trial
This is an interventional treatment trial for Leukemia focused on measuring B-cell chronic lymphocytic leukemia, stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia
Eligibility Criteria
Eligibility Criteria for Pre-Registration:
- Patients must be within 6 months of the initial flow cytometric confirmation of B-cell chronic lymphocytic leukemia (CLL). This interval begins with the initial flow cytometric confirmation of disease.
Clinical and immunophenotypic evidence of CLL including:
2.1 An absolute lymphocytosis of > 5,000/μL
- Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes.
- Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers.
- Additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density.
- Patients with bright surface immunoglobulin levels must have CD23 coexpression and absence of t(11;14) on interphase cytogenetics or have negative tumor protein staining for cyclin D1.
2.2 Staging - Patients must be in the low category (i.e., only stages 0 or I) of the modified three-stage Rai staging system as described in the protocol.
Patients should not have evidence of active disease as demonstrated by any of the following criteria:
- Splenomegaly and/or massive/progressive lymphadenopathy that would require therapy
- Presence of weight loss > 10% over the preceding 6 month period
- Grade 2 or 3 fatigue
- Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of infection
- Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.
- Prior Treatment: No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL.
- Age ≥ 18 years
- Performance Status 0 - 1.
- No HIV disease. Due to alterations in host immunity, patients known to have HIV infection may not be enrolled.
- Non-pregnant and non-nursing. Due to the unknown teratogenic potential of chemotherapy, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.
Required Initial Laboratory Values:
- Creatinine ≤ 1.5 x upper limit of normal
Eligibility Criteria for Registration (to Low-Risk Cohort or High-Risk Cohort Randomization between Early Intervention Versus Observation with Later Treatment)
- Successful determination of IgVH mutational status by reference laboratory.
Absence of progression of CLL, i.e., absence of the following:
- Progressive splenomegaly and/or lymphadenopathy on two independent measures spaced two weeks apart. If one assessment notes progression, this should be repeated prior to re-registration.
- Development of anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/μL).
- Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.
- Symptoms referable to CLL, including weight loss > 10% over the preceding 6 month period; grade 2 or 3 fatigue; or fevers > 100.5°F and/or night sweats for greater than 2 weeks without evidence of infection.
Required Laboratory Value:
- Creatinine ≤ 1.5 x upper limit of normal
Sites / Locations
- Regional Medical Center
- Clearview Cancer Institute
- Sparks Regional Medical Center
- Providence Saint Joseph Medical Center - Burbank
- Virginia K. Crosson Cancer Center at St. Jude Medical Center
- Memorial Medical Center
- Camino Medical Group - Treatment Center
- Palo Alto Medical Foundation
- University of California Davis Cancer Center
- Kaiser Permanente Medical Office -Vandever Medical Office
- Aurora Presbyterian Hospital
- Boulder Community Hospital
- Penrose Cancer Center at Penrose Hospital
- St. Anthony Central Hospital
- Porter Adventist Hospital
- Presbyterian - St. Luke's Medical Center
- St. Joseph Hospital
- Rose Medical Center
- CCOP - Colorado Cancer Research Program
- Swedish Medical Center
- St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
- North Colorado Medical Center
- Sky Ridge Medical Center
- Hope Cancer Care Center at Longmont United Hospital
- McKee Medical Center
- St. Mary - Corwin Regional Medical Center
- North Suburban Medical Center
- Exempla Lutheran Medical Center
- Manchester Memorial Hospital
- Tunnell Cancer Center at Beebe Medical Center
- CCOP - Christiana Care Health Services
- Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
- Walter Reed Army Medical Center
- Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
- Memorial Cancer Institute at Memorial Regional Hospital
- Ella Milbank Foshay Cancer Center at Jupiter Medical Center
- CCOP - Mount Sinai Medical Center
- Florida Hospital Cancer Institute at Florida Hospital Orlando
- M.D. Anderson Cancer Center at Orlando
- Sacred Heart Cancer Center at Sacred Heart Hospital
- West Florida Cancer Institute at West Florida Hospital - Pensacola
- Phoebe Cancer Center at Phoebe Putney Memorial Hospital
- John B. Amos Cancer Center
- Mountain States Tumor Institute at St. Luke's Regional Medical Center
- Saint Anthony's Hospital at Saint Anthony's Health Center
- Hematology Oncology Associates of Illinois - Berwyn
- Illinois CancerCare - Bloomington
- St. Joseph Medical Center
- Illinois CancerCare - Canton
- Illinois CancerCare - Carthage
- Memorial Hospital
- Robert H. Lurie Comprehensive Cancer Center at Northwestern University
- Hematology and Oncology Associates
- Rush University Medical Center
- University of Chicago Cancer Research Center
- Elmhurst Memorial Hospital
- Eureka Community Hospital
- Illinois CancerCare - Eureka
- Galesburg Clinic, PC
- Galesburg Cottage Hospital
- Illinois CancerCare - Galesburg
- Illinois CancerCare - Havana
- Mason District Hospital
- Kellogg Cancer Care Center
- Midwest Center for Hematology/Oncology
- Illinois CancerCare - Kewanee Clinic
- North Shore Oncology and Hematology Associates, Limited - Libertyville
- Illinois CancerCare - Macomb
- McDonough District Hospital
- Cardinal Bernardin Cancer Center at Loyola University Medical Center
- Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
- Illinois CancerCare - Monmouth
- OSF Holy Family Medical Center
- Good Samaritan Regional Health Center
- Edward Hospital Cancer Center
- La Grange Oncology Associates - Geneva
- Cancer Care and Hematology Specialists of Chicagoland - Niles
- BroMenn Regional Medical Center
- Community Cancer Center
- Illinois CancerCare - Community Cancer Center
- Community Hospital of Ottawa
- Oncology Hematology Associates of Central Illinois, PC - Ottawa
- Cancer Treatment Center at Pekin Hospital
- Illinois CancerCare - Pekin
- Proctor Hospital
- CCOP - Illinois Oncology Research Association
- Oncology Hematology Associates of Central Illinois, PC - Peoria
- Methodist Medical Center of Illinois
- OSF St. Francis Medical Center
- Illinois CancerCare - Peru
- Illinois Valley Community Hospital
- Illinois CancerCare - Princeton
- Perry Memorial Hospital
- Swedish-American Regional Cancer Center
- Hematology Oncology Associates - Skokie
- Illinois CancerCare - Spring Valley
- St. Margaret's Hospital
- Central Dupage Cancer Center
- St. Francis Hospital and Health Centers - Beech Grove Campus
- Community Hospital
- Reid Hospital & Health Care Services
- McFarland Clinic, PC
- Hematology Oncology Associates of the Quad Cities
- Medical Oncology and Hematology Associates - West Des Moines
- Genesis Regional Cancer Center at Genesis Medical Center
- Genesis Medical Center - West Campus
- Mercy Capitol Hospital
- CCOP - Iowa Oncology Research Association
- John Stoddard Cancer Center at Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates at John Stoddard Cancer Center
- Medical Oncology and Hematology Associates at Mercy Cancer Center
- Mercy Cancer Center at Mercy Medical Center - Des Moines
- John Stoddard Cancer Center at Iowa Lutheran Hospital
- Holden Comprehensive Cancer Center at University of Iowa
- Veterans Affairs Medical Center - Iowa City
- Siouxland Hematology-Oncology Associates, LLP
- Mercy Medical Center - Sioux City
- St. Luke's Regional Medical Center
- Cedar Valley Medical Specialists, PC - West Ridgeway Avenue
- Covenant Cancer Treatment Center
- Cancer Center of Kansas, PA - Chanute
- Cancer Center of Kansas, PA - Dodge City
- Cancer Center of Kansas, PA - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas, PA - Kingman
- Lawrence Memorial Hospital
- Southwest Medical Center
- Cancer Center of Kansas, PA - Newton
- Menorah Medical Center
- Saint Luke's Hospital - South
- Cancer Center of Kansas, PA - Parsons
- Cancer Center of Kansas, PA - Pratt
- Cancer Center of Kansas, PA - Salina
- Shawnee Mission Medical Center
- Cotton-O'Neil Cancer Center
- Cancer Center of Kansas, PA - Wellington
- Associates in Womens Health, PA - North Review
- Cancer Center of Kansas, PA - Medical Arts Tower
- Cancer Center of Kansas, PA - Wichita
- CCOP - Wichita
- Via Christi Cancer Center at Via Christi Regional Medical Center
- Wesley Medical Center
- Cancer Center of Kansas, PA - Winfield
- CancerCare of Maine at Eastern Maine Medical Center
- MaineGeneral Medical Center - Waterville
- Greenebaum Cancer Center at University of Maryland Medical Center
- Union Hospital Cancer Program at Union Hospital
- Massachusetts General Hospital
- Dana-Farber/Brigham and Women's Cancer Center
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
- Beth Israel Deaconess Medical Center
- Lahey Clinic Medical Center - Burlington
- Hickman Cancer Center at Bixby Medical Center
- Saint Joseph Mercy Cancer Center
- CCOP - Michigan Cancer Research Consortium
- Oakwood Cancer Center at Oakwood Hospital and Medical Center
- Green Bay Oncology, Limited - Escanaba
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Van Elslander Cancer Center at St. John Hospital and Medical Center
- Dickinson County Healthcare System
- Foote Memorial Hospital
- Borgess Medical Center
- West Michigan Cancer Center
- Bronson Methodist Hospital
- Haematology-Oncology Associates of Ohio and Michigan, PC
- Sparrow Regional Cancer Center
- St. Mary Mercy Hospital
- Community Cancer Center of Monroe
- Mercy Memorial Hospital - Monroe
- St. Joseph Mercy Oakland
- Mercy Regional Cancer Center at Mercy Hospital
- Seton Cancer Institute at Saint Mary's - Saginaw
- Oncology Care Associates, PLLC
- Providence Cancer Institute at Providence Hospital - Southfield Campus
- St. John Macomb Hospital
- Fairview Ridges Hospital
- Mercy and Unity Cancer Center at Mercy Hospital
- Fairview Southdale Hospital
- Mercy and Unity Cancer Center at Unity Hospital
- Hutchinson Area Health Care
- HealthEast Cancer Care at St. John's Hospital
- Minnesota Oncology Hematology, PA - Maplewood
- Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
- Hennepin County Medical Center - Minneapolis
- Veterans Affairs Medical Center - Minneapolis
- Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
- Mayo Clinic Cancer Center
- CentraCare Clinic - River Campus
- Coborn Cancer Center
- CCOP - Metro-Minnesota
- Park Nicollet Cancer Center
- Regions Hospital Cancer Care Center
- United Hospital
- St. Francis Cancer Center at St. Francis Medical Center
- Ridgeview Medical Center
- Minnesota Oncology Hematology, PA - Woodbury
- Saint Francis Medical Center
- Truman Medical Center - Hospital Hill
- Saint Luke's Cancer Institute at Saint Luke's Hospital
- St. Joseph Medical Center
- North Kansas City Hospital
- Parvin Radiation Oncology
- CCOP - Kansas City
- Research Medical Center
- Saint Luke's East - Lee's Summit
- Liberty Hospital
- Heartland Regional Medical Center
- Midwest Hematology Oncology Group, Incorporated
- Saint Louis University Cancer Center
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
- CCOP - St. Louis-Cape Girardeau
- David C. Pratt Cancer Center at St. John's Mercy
- CCOP - Cancer Research for the Ozarks
- St. John's Regional Health Center
- Hulston Cancer Center at Cox Medical Center South
- CCOP - Montana Cancer Consortium
- Hematology-Oncology Centers of the Northern Rockies - Billings
- Northern Rockies Radiation Oncology Center
- St. Vincent Healthcare Cancer Care Services
- Billings Clinic - Downtown
- Bozeman Deaconess Cancer Center
- St. James Healthcare Cancer Care
- Big Sky Oncology
- Great Falls Clinic - Main Facility
- Sletten Cancer Institute at Benefis Healthcare
- Northern Montana Hospital
- St. Peter's Hospital
- Glacier Oncology, PLLC
- Kalispell Medical Oncology at KRMC
- Kalispell Regional Medical Center
- Community Medical Center
- Guardian Oncology and Center for Wellness
- Montana Cancer Specialists at Montana Cancer Center
- Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
- CCOP - Missouri Valley Cancer Consortium
- Methodist Estabrook Cancer Center
- Immanuel Medical Center
- Alegant Health Cancer Center at Bergan Mercy Medical Center
- Creighton University Medical Center
- Veterans Affairs Medical Center - East Orange
- Hunterdon Regional Cancer Center at Hunterdon Medical Center
- Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
- Cancer Institute of New Jersey at Cooper - Voorhees
- Fox Chase Virtua Health Cancer Program at Virtua West Jersey
- University of New Mexico Cancer Center
- New Mexico Cancer Care Associates
- CCOP - Hematology-Oncology Associates of Central New York
- Adirondack Cancer Care - Glens Falls
- Monter Cancer Center of the North Shore-LIJ Health System
- CCOP - North Shore University Hospital
- Don Monti Comprehensive Cancer Center at North Shore University Hospital
- Long Island Jewish Medical Center
- New York Weill Cornell Cancer Center at Cornell University
- James P. Wilmot Cancer Center at University of Rochester Medical Center
- Stony Brook University Cancer Center
- SUNY Upstate Medical University Hospital
- Veterans Affairs Medical Center - Syracuse
- Mission Hospitals - Memorial Campus
- Batte Cancer Center at Northeast Medical Center
- Wayne Memorial Hospital, Incorporated
- Pardee Memorial Hospital
- Kinston Medical Specialists
- Wake Forest University Comprehensive Cancer Center
- Bismarck Cancer Center
- Medcenter One Hospital Cancer Care Center
- Mid Dakota Clinic, PC
- St. Alexius Medical Center Cancer Center
- Summa Center for Cancer Care at Akron City Hospital
- Mary Rutan Hospital
- Wood County Oncology Center
- Adena Regional Medical Center
- MetroHealth Cancer Care Center at MetroHealth Medical Center
- North Coast Cancer Care - Clyde
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
- Riverside Methodist Hospital Cancer Care
- CCOP - Columbus
- Grant Medical Center Cancer Care
- Mount Carmel Health - West Hospital
- Doctors Hospital at Ohio Health
- Grandview Hospital
- Good Samaritan Hospital
- David L. Rike Cancer Center at Miami Valley Hospital
- Samaritan North Cancer Care Center
- CCOP - Dayton
- Grady Memorial Hospital
- Hematology Oncology Center
- Blanchard Valley Medical Associates
- Middletown Regional Hospital
- Wayne Hospital
- Charles F. Kettering Memorial Hospital
- Fairfield Medical Center
- St. Rita's Medical Center
- Lima Memorial Hospital
- Strecker Cancer Center at Marietta Memorial Hospital
- Northwest Ohio Oncology Center
- St. Luke's Hospital
- Licking Memorial Cancer Care Program at Licking Memorial Hospital
- St. Charles Mercy Hospital
- Toledo Clinic - Oregon
- North Coast Cancer Care, Incorporated
- Mercy Medical Center
- Community Hospital of Springfield and Clark County
- Flower Hospital Cancer Center
- Mercy Hospital of Tiffin
- Toledo Hospital
- St. Vincent Mercy Medical Center
- Medical University of Ohio Cancer Center
- CCOP - Toledo Community Hospital
- St. Anne Mercy Hospital
- Toledo Clinic, Incorporated - Main Clinic
- UVMC Cancer Care Center at Upper Valley Medical Center
- Fulton County Health Center
- Mount Carmel St. Ann's Cancer Center
- Clinton Memorial Hospital
- Ruth G. McMillan Cancer Center at Greene Memorial Hospital
- Genesis - Good Samaritan Hospital
- Providence Milwaukie Hospital
- Providence Cancer Center at Providence Portland Medical Center
- CCOP - Columbia River Oncology Program
- Providence St. Vincent Medical Center
- Kaiser Permanente Health Care - Portland
- Legacy Meridian Park Hospital
- Geisinger Cancer Institute at Geisinger Health
- Geisinger Hazleton Cancer Center
- Riddle Memorial Hospital Cancer Center
- Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
- Joan Karnell Cancer Center at Pennsylvania Hospital
- Cancer Center at Phoenixville Hospital
- Geisinger Medical Group - Scenery Park
- Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
- Memorial Hospital of Rhode Island
- Hollings Cancer Center at Medical University of South Carolina
- McLeod Regional Medical Center
- CCOP - Greenville
- Mountainview Medical
- Fletcher Allen Health Care - University Health Center Campus
- Fredericksburg Oncology, Incorporated
- St. Joseph Cancer Center
- Olympic Hematology and Oncology
- Columbia Basin Hematology
- Harrison Poulsbo Hematology and Onocology
- Minor and James Medical, PLLC
- Group Health Central Hospital
- Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
- Polyclinic First Hill
- University Cancer Center at University of Washington Medical Center
- Cancer Care Northwest - Spokane South
- Evergreen Hematology and Oncology, PS
- Southwest Washington Medical Center Cancer Center
- Marshfield Clinic - Chippewa Center
- Marshfield Clinic Cancer Care at Regional Cancer Center
- Central Wisconsin Cancer Program at Agnesian HealthCare
- Oncology Alliance, SC - Milwaukee - East
- Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
- Green Bay Oncology, Limited at St. Mary's Hospital
- St. Mary's Hospital Medical Center - Green Bay
- St. Vincent Hospital Regional Cancer Center
- Holy Family Memorial Medical Center Cancer Care Center
- Bay Area Cancer Care Center at Bay Area Medical Center
- Marshfield Clinic - Marshfield Center
- Saint Joseph's Hospital
- Marshfield Clinic - Lakeland Center
- Regional Cancer Center at Oconomowoc Memorial Hospital
- Green Bay Oncology, Limited - Oconto Falls
- Ministry Medical Group at Saint Mary's Hospital
- Marshfield Clinic - Indianhead Center
- Vince Lombardi Cancer Clinic - Sheboygan
- Saint Michael's Hospital Cancer Center
- Green Bay Oncology, Limited - Sturgeon Bay
- Waukesha Memorial Hospital Regional Cancer Center
- Marshfield Clinic - Weston Center
- Marshfield Clinic - Wisconsin Rapids Center
- Welch Cancer Center at Sheridan Memorial Hospital
- CancerCare Manitoba
- Moncton Hospital
- Nova Scotia Cancer Centre
- Margaret and Charles Juravinski Cancer Centre
- Northeastern Ontario Regional Cancer Centre
- Edmond Odette Cancer Centre at Sunnybrook
- Maisonneuve-Rosemont Hospital
- Allan Blair Cancer Centre at Pasqua Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I
Arm II
Patients receive rituximab IV over 4 hours on days 1, 3, and 5 of week 1 and then on day 1 of weeks 5, 9, 13, 17, and 21. Patients also receive fludarabine phosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in arm I. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.