Fludarabine and Rituximab With or Without Lenalidomide or Cyclophosphamide in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia
About this trial
This is an interventional treatment trial for Stage I Chronic Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
Specific diagnosis of B-cell CLL:
An absolute lymphocytosis of > 5,000/uL
- Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes
- Bone marrow examination must include at least a unilateral aspirate and biopsy; the aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL; overall cellularity must be normocellular or hypercellular
- Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (cluster of differentiation [CD]19, 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 kappa or lambda and have surface immunoglobulin expression of low density; patients with bright surface immunoglobulin levels must have CD23 co-expression
Patients must have symptomatic and active intermediate or high-risk categories of the modified three-stage Rai staging system:
- Not eligible: low risk, Rai stage 0, lymphocytes (L) in blood (> 5000/uL) and marrow (> 30%) only
- Intermediate risk, Rai stage I, L + enlarged lymph nodes (LN)
- Intermediate risk, Rai stage II, L + spleen and/or liver (LN + or -)
- High risk, Rai stage III, L + anemia (hemoglobin < 11 gm/dL)
- High risk, Rai stage IV, L + thrombocytopenia (platelets < 100,000/uL)
Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:
- Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy
- Presence of weight loss > 10% over the preceding 6 month period
- Grade 2 or 3 fatigue
- Fevers > 100.5 degrees Fahrenheit (°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
- No prior therapy for CLL, including no corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
- No medical condition requiring chronic use of oral corticosteroids
- Performance status 0 - 2
- Patients with human immunodeficiency virus (HIV) infection may be eligible provided they meet the following criteria: no evidence of infection with hepatitis B or C; CD4+ cell count > 350/mm^3; no evidence of resistant strains of HIV; if not on anti-HIV therapy, an HIV viral load < 10,000 copies HIV ribonucleic acid (RNA)/mL; if on HIV therapy, HIV viral load < 50 copies HIV RNA/mL; and no history of acquired immune deficiency syndrome (AIDS)-defining condition; patients receiving concurrent zidovudine or stavudine may not be enrolled
- Non-pregnant and non-nursing
- In females of child-bearing potential randomized to Arm B or assigned to Arm D, a negative urine or serum pregnancy test with a sensitivity of at least 25 mIU/mL will be required: 1) 10-14 days prior to beginning lenalidomide consolidation therapy; and 2) within 24 hours prior to the first dose of lenalidomide consolidation therapy; in addition, females of childbearing potential in Arm B and Arm D with regular menses must have a pregnancy test performed weekly during the first 28 days of treatment, and then every 28 days while taking lenalidomide (including breaks in lenalidomide), at discontinuation of lenalidomide, and then 28 days following discontinuation of lenalidomide; if menses are irregular, a pregnancy test must be performed weekly during the first 28 days of treatment, and then every 14 days while taking lenalidomide, at discontinuation of lenalidomide, and at 14 and 28 days after discontinuation of lenalidomide; additionally, females of childbearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO reliable methods of birth control - one highly effective method (intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, or partner's vasectomy), and one additional effective method (latex condom, diaphragm, or cervical cap) - AT THE SAME TIME, at least 4 weeks before she begins lenalidomide therapy, while participating in the study, and for at least 4 weeks after completing lenalidomide therapy; "females of childbearing potential" is defined as a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy, or who has had menses at any time in the preceding 24 consecutive months (not been naturally postmenopausal for at least 24 consecutive months)
- Male patients randomized to Arm B or reassigned to Arm D must agree not to father a child and to use a latex condom during any sexual contact with females of childbearing potential while taking lenalidomide and for at least 4 weeks following completion of lenalidomide therapy, even if the patient have undergone a successful vasectomy
- All patients randomized to Arm B or reassigned to Arm D must be counseled by a trained counselor every 28 days during consolidation therapy about pregnancy precautions and risks of fetal exposure
- Creatinine =< 1.5 x upper limit of normal
Sites / Locations
- Mayo Clinic in Arizona
- PCR Oncology
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Palo Alto Medical Foundation-Camino Division
- Palo Alto Medical Foundation Health Care
- UCSF Medical Center-Mount Zion
- Hartford Hospital
- Smilow Cancer Hospital Care Center at Saint Francis
- Norwalk Hospital
- Smilow Cancer Hospital-Torrington Care Center
- Beebe Medical Center
- Christiana Care Health System-Christiana Hospital
- MedStar Georgetown University Hospital
- Sibley Memorial Hospital
- Jupiter Medical Center
- Mount Sinai Medical Center
- Orlando Health Cancer Institute
- Saint Anthony's Health
- Rush - Copley Medical Center
- MacNeal Hospital and Cancer Center
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Graham Hospital Association
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Memorial Hospital
- Hematology and Oncology Associates
- Northwestern University
- University of Chicago Comprehensive Cancer Center
- Weiss Memorial Hospital
- Decatur Memorial Hospital
- Heartland Cancer Research NCORP
- Ascension Alexian Brothers - Elk Grove Village
- Eureka Hospital
- Illinois CancerCare-Eureka
- NorthShore University HealthSystem-Evanston Hospital
- Galesburg Cottage Hospital
- Illinois CancerCare-Galesburg
- Illinois CancerCare-Havana
- Mason District Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- Hopedale Medical Complex - Hospital
- Midwest Center for Hematology Oncology
- Duly Health and Care Joliet
- Presence Saint Mary's Hospital
- Illinois CancerCare-Kewanee Clinic
- AMG Libertyville - Oncology
- Illinois CancerCare-Macomb
- Mcdonough District Hospital
- Loyola University Medical Center
- Holy Family Medical Center
- Illinois CancerCare-Monmouth
- Good Samaritan Regional Health Center
- DuPage Medical Group-Ogden
- Illinois Cancer Specialists-Niles
- Bromenn Regional Medical Center
- Carle Cancer Institute Normal
- Illinois CancerCare-Community Cancer Center
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Pekin Hospital
- Proctor Hospital
- Illinois CancerCare-Peoria
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Illinois Valley Hospital
- Illinois CancerCare-Princeton
- Perry Memorial Hospital
- Swedish American Hospital
- OSF Saint Anthony Medical Center
- Hematology Oncology Associates of Illinois - Skokie
- Illinois CancerCare-Spring Valley
- Saint Margaret's Hospital
- Memorial Medical Center
- Carle Cancer Center
- Northwestern Medicine Cancer Center Warrenville
- Franciscan Saint Francis Health-Beech Grove
- Elkhart Clinic
- Michiana Hematology Oncology PC-Elkhart
- Elkhart General Hospital
- Fort Wayne Medical Oncology and Hematology Inc-Parkview
- Community Howard Regional Health
- IU Health La Porte Hospital
- Franciscan Saint Anthony Health-Michigan City
- Michiana Hematology Oncology PC-Mishawaka
- Saint Joseph Regional Medical Center-Mishawaka
- Michiana Hematology Oncology PC-Plymouth
- Reid Health
- Memorial Hospital of South Bend
- Michiana Hematology Oncology PC-South Bend
- South Bend Clinic
- Northern Indiana Cancer Research Consortium
- Michiana Hematology Oncology PC-Westville
- McFarland Clinic PC - Ames
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Capitol
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Mercy Medical Center - Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- Iowa City VA Healthcare System
- Ottumwa Regional Health Center
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- HaysMed University of Kansas Health System
- Hutchinson Regional Medical Center
- Providence Medical Center
- University of Kansas Cancer Center
- Lawrence Memorial Hospital
- Olathe Cancer Center
- Menorah Medical Center
- Radiation Oncology Practice Corporation Southwest
- Saint Luke's South Hospital
- Ascension Via Christi - Pittsburg
- Kansas City NCI Community Oncology Research Program
- Salina Regional Health Center
- Advent Health - Shawnee Mission Medical Center
- Cotton O'Neil Cancer Center / Stormont Vail Health
- University of Kansas Health System Saint Francis Campus
- Wesley Medical Center
- Doctors Carrol, Sheth, Raghavan
- Harold Alfond Center for Cancer Care
- Eastern Maine Medical Center
- University of Maryland/Greenebaum Cancer Center
- Walter Reed National Military Medical Center
- Christiana Care - Union Hospital
- Unspecified Site
- Lahey Hospital and Medical Center
- Henry Ford Hospital
- Green Bay Oncology - Escanaba
- Cancer Research Consortium of West Michigan NCORP
- Green Bay Oncology - Iron Mountain
- Bronson Methodist Hospital
- West Michigan Cancer Center
- Borgess Medical Center
- Lakeland Hospital Niles
- Lakeland Medical Center Saint Joseph
- Marie Yeager Cancer Center
- Munson Medical Center
- Fairview Ridges Hospital
- Mercy Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Hutchinson Area Health Care
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Virginia Piper Cancer Institute
- Hennepin County Medical Center
- Minneapolis VA Medical Center
- North Memorial Medical Health Center
- Mayo Clinic in Rochester
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Saint Francis Medical Center
- Southeast Cancer Center
- University of Missouri - Ellis Fischel
- Centerpoint Medical Center LLC
- Capital Region Southwest Campus
- Truman Medical Centers
- Saint Luke's Hospital of Kansas City
- Radiation Oncology Practice Corporation South
- Saint Joseph Health Center
- North Kansas City Hospital
- Heartland Hematology and Oncology Associates Incorporated
- Research Medical Center
- Radiation Oncology Practice Corporation - North
- Saint Luke's East - Lee's Summit
- Liberty Radiation Oncology Center
- Heartland Regional Medical Center
- Saint Joseph Oncology Inc
- SSM Health Saint Louis University Hospital
- Saint Louis Cancer and Breast Institute-South City
- Washington University School of Medicine
- Missouri Baptist Medical Center
- Center for Cancer Care and Research
- Comprehensive Cancer Care PC
- Mercy Hospital Saint Louis
- Saint Louis-Cape Girardeau CCOP
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Billings Clinic Cancer Center
- Saint Vincent Healthcare
- Montana Cancer Consortium NCORP
- Saint Vincent Frontier Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Northern Montana Hospital
- Saint Peter's Community Hospital
- Glacier Oncology PLLC
- Kalispell Medical Oncology
- Kalispell Regional Medical Center
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- CHI Health Saint Francis
- Nebraska Methodist Hospital
- University of Nebraska Medical Center
- University Medical Center of Southern Nevada
- Nevada Cancer Research Foundation NCORP
- New Hampshire Oncology Hematology PA-Concord
- LRGHealthcare-Lakes Region General Hospital
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
- Norris Cotton Cancer Center-Manchester
- Solinsky Center for Cancer Care
- Cooper Hospital University Medical Center
- Veterans Adminstration New Jersey Health Care System
- Virtua Memorial
- Rutgers Cancer Institute of New Jersey
- Saint Joseph's Regional Medical Center
- Virtua Voorhees
- Lovelace Medical Center-Saint Joseph Square
- University of New Mexico Cancer Center
- Memorial Medical Center - Las Cruces
- Montefiore Medical Center-Weiler Hospital
- Montefiore Medical Center - Moses Campus
- Hematology Oncology Associates of Central New York-East Syracuse
- Northwell Health NCORP
- Northwell Health/Center for Advanced Medicine
- North Shore University Hospital
- Long Island Jewish Medical Center
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- Mount Sinai Hospital
- NYP/Weill Cornell Medical Center
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical University
- Randolph Hospital
- Mission Hospital
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Wayne Memorial Hospital
- Cone Health Cancer Center
- East Carolina University
- Margaret R Pardee Memorial Hospital
- Vidant Oncology-Kinston
- Annie Penn Memorial Hospital
- Iredell Memorial Hospital
- Wake Forest University Health Sciences
- Mary Rutan Hospital
- Aultman Health Foundation
- Adena Regional Medical Center
- Case Western Reserve University
- MetroHealth Medical Center
- Cleveland Clinic Foundation
- Ohio State University Comprehensive Cancer Center
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- Grant Medical Center
- Mount Carmel Health Center West
- Doctors Hospital
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Miami Valley Hospital North
- Dayton NCI Community Oncology Research Program
- Grady Memorial Hospital
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Fairfield Medical Center
- Marietta Memorial Hospital
- Knox Community Hospital
- Licking Memorial Hospital
- Springfield Regional Medical Center
- Upper Valley Medical Center
- Saint Ann's Hospital
- Clinton Memorial Hospital
- Greene Memorial Hospital
- Genesis Healthcare System Cancer Care Center
- Bryn Mawr Hospital
- Geisinger Medical Center
- Easton Hospital
- Geisinger Medical Center-Cancer Center Hazleton
- Penn State Milton S Hershey Medical Center
- Lewistown Hospital
- Paoli Memorial Hospital
- University of Pennsylvania/Abramson Cancer Center
- Fox Chase Cancer Center
- Pottstown Hospital
- Geisinger Medical Group
- Mount Nittany Medical Center
- Geisinger Wyoming Valley/Henry Cancer Center
- Geisinger South Wilkes-Barre
- Lankenau Medical Center
- Main Line Health NCORP
- Prisma Health Cancer Institute - Spartanburg
- Medical University of South Carolina
- Prisma Health Cancer Institute - Easley
- McLeod Regional Medical Center
- Greenville Health System Cancer Institute-Andrews
- Saint Francis Hospital
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Greenville Memorial Hospital
- Prisma Health Cancer Institute - Eastside
- Self Regional Healthcare
- Prisma Health Cancer Institute - Greer
- Prisma Health Cancer Institute - Seneca
- Thompson Cancer Survival Center
- Vanderbilt University/Ingram Cancer Center
- Baylor University Medical Center
- Central Vermont Medical Center/National Life Cancer Treatment
- University of Vermont and State Agricultural College
- Norris Cotton Cancer Center-North
- Danville Regional Medical Center
- Sovah Health Martinsville
- Virginia Commonwealth University/Massey Cancer Center
- West Virginia University Healthcare
- Wheeling Hospital/Schiffler Cancer Center
- Marshfield Clinic-Chippewa Center
- HSHS Sacred Heart Hospital
- Marshfield Clinic Cancer Center at Sacred Heart
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- UW Cancer Center Johnson Creek
- Gundersen Lutheran Medical Center
- University of Wisconsin Carbone Cancer Center
- Holy Family Memorial Hospital
- Bay Area Medical Center
- Marshfield Medical Center-Marshfield
- Marshfield Medical Center
- Marshfield Clinic-Minocqua Center
- ProHealth Oconomowoc Memorial Hospital
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Ascension Saint Mary's Hospital
- Saint Mary's Hospital
- Marshfield Medical Center-Rice Lake
- HSHS Saint Nicholas Hospital
- Ascension Saint Michael's Hospital
- Green Bay Oncology - Sturgeon Bay
- ProHealth Waukesha Memorial Hospital
- Diagnostic and Treatment Center
- Marshfield Medical Center - Weston
- Marshfield Clinic - Wisconsin Rapids Center
- Rocky Mountain Oncology
- Welch Cancer Center
- Tom Baker Cancer Centre
- Cross Cancer Institute
- CancerCare Manitoba
- QEII Health Sciences Centre/Nova Scotia Health Authority
- Juravinski Cancer Centre at Hamilton Health Sciences
- University Health Network-Princess Margaret Hospital
- CSSS Champlain-Charles Le Moyne
- McGill University Health Centre at Royal Victoria Hospital
- CHU de Quebec-Hopital du Saint-Sacrement (HSS)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Experimental
Experimental
Arm A (rituximab, fludarabine phosphate)
Arm B (rituximab, fludarabine phosphate, lenalidomide)
Arm C (rituximab, fludarabine phosphate, cyclophosphamide)
Arm D (rituximab, fludarabine, cyclophosphamide, lenalidomide)
Participants receive induction therapy (every 28 days for up to 6 cycles) of: Patients receive rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5.
Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 1-4 hours on days 1 (50 mg/m^2), 3 (325 mg/m^2), and 5 (375 mg/m^2) of course 1 and on day 1 (375 mg/m^2) of all subsequent courses. Patients also receive fludarabine phosphate 25 mg/m^2/day IV over 30 minutes or PO on days 1-5. Participants without progression receive consolidation therapy lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6 PO QD on days 1-21 of 28 day cycle.
Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab IV over 4 hours on days 1 (50mg/m^2) and 3 (325 mg/m^2) of course 1 and on day 1 (500 mg/m^2) of all subsequent courses. Patients then receive fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) followed by cyclophosphamide (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) IV piggyback over 30 minutes on days 1-3.
Patients receive the first course of induction therapy as in Arm A or B before being re-assigned to Arm D. Beginning in course 2, patients receive rituximab IV (500 mg/m^2) on day 1 and fludarabine phosphate (age < 70: 25 mg/m^2/day; age >= 70: 20 mg/m^2/day) IV piggyback over 30 minutes or PO (32 mg/m^2/day) and cyclophosphamide IV (age < 70: 250 mg/m^2/day; age >= 70: 150 mg/m^2/day) piggyback over 30 minutes on days 1-3. Participants without progression receive consolidation therapy: lenalidomide 5mg/day cycle 1, 10 mg/day cycles 2-6PO QD on days 1-21 of 28 day cycle.