AzTrials
AzTrials

Stage I Chronic Lymphocytic LeukemiaPhase 2NCT00602459

Fludarabine and Rituximab With or Without Lenalidomide or Cyclophosphamide in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia

A Phase 2 study testing Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Stage I Chronic Lymphocytic Leukemia and Stage II Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 364 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This randomized phase II trial studies how well fludarabine (fludarabine phosphate) and rituximab with or without lenalidomide or cyclophosphamide work in treating patients with symptomatic chronic lymphocytic leukemia. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
418 participants
Where
364 sitesin 2 countries
Study dates
15 Jan 2008to 15 Apr 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

None listed.

Trial locations and contacts

364 sites in 2 countries.

309 sites in 2 countries

United States300 sites

  • Lovelace Medical Center-Saint Joseph Square

    Albuquerque, New Mexico, 87102

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • Saint Anthony's Health

    Alton, Illinois, 62002

  • McFarland Clinic PC - Ames

    Ames, Iowa, 50010

  • PCR Oncology

    Arroyo Grande, California, 93420

  • Randolph Hospital

    Asheboro, North Carolina, 27203

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • Rush - Copley Medical Center

    Aurora, Illinois, 60504

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Franciscan Saint Francis Health-Beech Grove

    Beech Grove, Indiana, 46107

  • Mary Rutan Hospital

    Bellefontaine, Ohio, 43311

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • MacNeal Hospital and Cancer Center

    Berwyn, Illinois, 60402

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • Saint Vincent Healthcare

    Billings, Montana, 59101

  • Montana Cancer Consortium NCORP

    Billings, Montana, 59102

  • Saint Vincent Frontier Cancer Center

    Billings, Montana, 59102

  • Saint Joseph Medical Center

    Bloomington, Illinois, 61701

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Bozeman Deaconess Hospital

    Bozeman, Montana, 59715

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Providence Saint Joseph Medical Center/Disney Family Cancer Center

    Burbank, California, 91505

  • Lahey Hospital and Medical Center

    Burlington, Massachusetts, 01805

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Saint James Community Hospital and Cancer Treatment Center

    Butte, Montana, 59701

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Graham Hospital Association

    Canton, Illinois, 61520

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Southeast Cancer Center

    Cape Girardeau, Missouri, 63703

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Memorial Hospital

    Carthage, Illinois, 62321

  • Rocky Mountain Oncology

    Casper, Wyoming, 82609

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Hematology and Oncology Associates

    Chicago, Illinois, 60611

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Weiss Memorial Hospital

    Chicago, Illinois, 60640

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Marshfield Clinic-Chippewa Center

    Chippewa Falls, Wisconsin, 54729

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Medical Oncology and Hematology Associates-West Des Moines

    Clive, Iowa, 50325

  • University of Missouri - Ellis Fischel

    Columbia, Missouri, 65212

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Riverside Methodist Hospital

    Columbus, Ohio, 43214

  • Columbus NCI Community Oncology Research Program

    Columbus, Ohio, 43215

  • Grant Medical Center

    Columbus, Ohio, 43215

  • Mount Carmel Health Center West

    Columbus, Ohio, 43222

  • Doctors Hospital

    Columbus, Ohio, 43228

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Danville Regional Medical Center

    Danville, Virginia, 24541

  • Grandview Hospital

    Dayton, Ohio, 45405

  • Good Samaritan Hospital - Dayton

    Dayton, Ohio, 45406

  • Miami Valley Hospital

    Dayton, Ohio, 45409

  • Miami Valley Hospital North

    Dayton, Ohio, 45415

  • Dayton NCI Community Oncology Research Program

    Dayton, Ohio, 45459

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Heartland Cancer Research NCORP

    Decatur, Illinois, 62526

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • Mercy Capitol

    Des Moines, Iowa, 50307

  • Iowa Methodist Medical Center

    Des Moines, Iowa, 50309

  • Iowa-Wide Oncology Research Coalition NCORP

    Des Moines, Iowa, 50309

  • Medical Oncology and Hematology Associates-Des Moines

    Des Moines, Iowa, 50309

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Mission Cancer and Blood - Laurel

    Des Moines, Iowa, 50314

  • Iowa Lutheran Hospital

    Des Moines, Iowa, 50316

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Prisma Health Cancer Institute - Easley

    Easley, South Carolina, 29640

  • Veterans Adminstration New Jersey Health Care System

    East Orange, New Jersey, 07018-1095

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • Easton Hospital

    Easton, Pennsylvania, 18042

  • HSHS Sacred Heart Hospital

    Eau Claire, Wisconsin, 54701

  • Marshfield Clinic Cancer Center at Sacred Heart

    Eau Claire, Wisconsin, 54701

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Ascension Alexian Brothers - Elk Grove Village

    Elk Grove Village, Illinois, 60007

  • Elkhart Clinic

    Elkhart, Indiana, 46514-2098

  • Michiana Hematology Oncology PC-Elkhart

    Elkhart, Indiana, 46514

  • Elkhart General Hospital

    Elkhart, Indiana, 46515

  • Christiana Care - Union Hospital

    Elkton, Maryland, 21921

  • Green Bay Oncology - Escanaba

    Escanaba, Michigan, 49829

  • Eureka Hospital

    Eureka, Illinois, 61530

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Blanchard Valley Hospital

    Findlay, Ohio, 45840

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Atrium Medical Center-Middletown Regional Hospital

    Franklin, Ohio, 45005-1066

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Galesburg Cottage Hospital

    Galesburg, Illinois, 61401

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • CHI Health Saint Francis

    Grand Island, Nebraska, 68803

  • Cancer Research Consortium of West Michigan NCORP

    Grand Rapids, Michigan, 49503

  • Benefis Healthcare- Sletten Cancer Institute

    Great Falls, Montana, 59405

  • Great Falls Clinic

    Great Falls, Montana, 59405

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Green Bay Oncology Limited at Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • Cone Health Cancer Center

    Greensboro, North Carolina, 27403

  • East Carolina University

    Greenville, North Carolina, 27834

  • Wayne Hospital

    Greenville, Ohio, 45331

  • Greenville Health System Cancer Institute-Andrews

    Greenville, South Carolina, 29601

  • Saint Francis Hospital

    Greenville, South Carolina, 29601

  • Prisma Health Cancer Institute - Butternut

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Self Regional Healthcare

    Greenwood, South Carolina, 29646

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Hartford Hospital

    Hartford, Connecticut, 06102

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • Illinois CancerCare-Havana

    Havana, Illinois, 62644

  • Mason District Hospital

    Havana, Illinois, 62644

  • Northern Montana Hospital

    Havre, Montana, 59501

  • HaysMed University of Kansas Health System

    Hays, Kansas, 67601

  • Geisinger Medical Center-Cancer Center Hazleton

    Hazleton, Pennsylvania, 18201

  • Saint Peter's Community Hospital

    Helena, Montana, 59601

  • Margaret R Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • Hematology Oncology Associates of Illinois-Highland Park

    Highland Park, Illinois, 60035

  • Hopedale Medical Complex - Hospital

    Hopedale, Illinois, 61747

  • Hutchinson Regional Medical Center

    Hutchinson, Kansas, 67502

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • Centerpoint Medical Center LLC

    Independence, Missouri, 64057

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Iowa City VA Healthcare System

    Iowa City, Iowa, 52246

  • Green Bay Oncology - Iron Mountain

    Iron Mountain, Michigan, 49801

  • Capital Region Southwest Campus

    Jefferson City, Missouri, 65109

  • UW Cancer Center Johnson Creek

    Johnson Creek, Wisconsin, 53038

  • Midwest Center for Hematology Oncology

    Joliet, Illinois, 60432

  • Duly Health and Care Joliet

    Joliet, Illinois, 60435

  • Jupiter Medical Center

    Jupiter, Florida, 33458

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Borgess Medical Center

    Kalamazoo, Michigan, 49048

  • Glacier Oncology PLLC

    Kalispell, Montana, 59901

  • Kalispell Medical Oncology

    Kalispell, Montana, 59901

  • Kalispell Regional Medical Center

    Kalispell, Montana, 59901

  • Presence Saint Mary's Hospital

    Kankakee, Illinois, 60901

  • Providence Medical Center

    Kansas City, Kansas, 66112

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Truman Medical Centers

    Kansas City, Missouri, 64108

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • Radiation Oncology Practice Corporation South

    Kansas City, Missouri, 64114

  • Saint Joseph Health Center

    Kansas City, Missouri, 64114

  • North Kansas City Hospital

    Kansas City, Missouri, 64116

  • Heartland Hematology and Oncology Associates Incorporated

    Kansas City, Missouri, 64118

  • Research Medical Center

    Kansas City, Missouri, 64132

  • Radiation Oncology Practice Corporation - North

    Kansas City, Missouri, 64154

  • Kettering Medical Center

    Kettering, Ohio, 45429

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • Vidant Oncology-Kinston

    Kinston, North Carolina, 28501

  • Thompson Cancer Survival Center

    Knoxville, Tennessee, 37916

  • Community Howard Regional Health

    Kokomo, Indiana, 46904

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • IU Health La Porte Hospital

    La Porte, Indiana, 46350

  • LRGHealthcare-Lakes Region General Hospital

    Laconia, New Hampshire, 03246

  • Northwell Health NCORP

    Lake Success, New York, 11042

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • Memorial Medical Center - Las Cruces

    Las Cruces, New Mexico, 88011

  • University Medical Center of Southern Nevada

    Las Vegas, Nevada, 89102

  • Nevada Cancer Research Foundation NCORP

    Las Vegas, Nevada, 89169

  • Lawrence Memorial Hospital

    Lawrence, Kansas, 66044

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Saint Luke's East - Lee's Summit

    Lee's Summit, Missouri, 64086

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Lewistown Hospital

    Lewistown, Pennsylvania, 17044

  • Liberty Radiation Oncology Center

    Liberty, Missouri, 64068

  • AMG Libertyville - Oncology

    Libertyville, Illinois, 60048

  • Doctors Carrol, Sheth, Raghavan

    Louisville, Kentucky, 40215

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Mcdonough District Hospital

    Macomb, Illinois, 61455

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Norris Cotton Cancer Center-Manchester

    Manchester, New Hampshire, 03102

  • Solinsky Center for Cancer Care

    Manchester, New Hampshire, 03103

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Holy Family Memorial Hospital

    Manitowoc, Wisconsin, 54221

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Marshfield Medical Center

    Marshfield, Wisconsin, 54449

  • Sovah Health Martinsville

    Martinsville, Virginia, 24115

  • Loyola University Medical Center

    Maywood, Illinois, 60153

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Franciscan Saint Anthony Health-Michigan City

    Michigan City, Indiana, 46360

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Virginia Piper Cancer Institute

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Minneapolis VA Medical Center

    Minneapolis, Minnesota, 55417

  • Marshfield Clinic-Minocqua Center

    Minocqua, Wisconsin, 54548

  • Michiana Hematology Oncology PC-Mishawaka

    Mishawaka, Indiana, 46545

  • Saint Joseph Regional Medical Center-Mishawaka

    Mishawaka, Indiana, 46545

  • Montana Cancer Specialists

    Missoula, Montana, 59802

  • Saint Patrick Hospital - Community Hospital

    Missoula, Montana, 59802

  • Holy Family Medical Center

    Monmouth, Illinois, 61462

  • Illinois CancerCare-Monmouth

    Monmouth, Illinois, 61462

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • Virtua Memorial

    Mount Holly, New Jersey, 08060

  • Good Samaritan Regional Health Center

    Mount Vernon, Illinois, 62864

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • Palo Alto Medical Foundation-Camino Division

    Mountain View, California, 94040

  • DuPage Medical Group-Ogden

    Naperville, Illinois, 60563

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Mount Sinai Hospital

    New York, New York, 10029

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Licking Memorial Hospital

    Newark, Ohio, 43055

  • Illinois Cancer Specialists-Niles

    Niles, Illinois, 60714

  • Lakeland Hospital Niles

    Niles, Michigan, 49120

  • Bromenn Regional Medical Center

    Normal, Illinois, 61761

  • Carle Cancer Institute Normal

    Normal, Illinois, 61761

  • Illinois CancerCare-Community Cancer Center

    Normal, Illinois, 61761

  • Norwalk Hospital

    Norwalk, Connecticut, 06856

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • Saint Vincent Hospital Cancer Center at Oconto Falls

    Oconto Falls, Wisconsin, 54154

  • Olathe Cancer Center

    Olathe, Kansas, 66061

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Orlando Health Cancer Institute

    Orlando, Florida, 32806

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • Ottawa Regional Hospital and Healthcare Center

    Ottawa, Illinois, 61350

  • Ottumwa Regional Health Center

    Ottumwa, Iowa, 52501

  • Menorah Medical Center

    Overland Park, Kansas, 66209

  • Radiation Oncology Practice Corporation Southwest

    Overland Park, Kansas, 66210

  • Saint Luke's South Hospital

    Overland Park, Kansas, 66213

  • Palo Alto Medical Foundation Health Care

    Palo Alto, California, 94301

  • Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301

  • Saint Joseph's Regional Medical Center

    Paterson, New Jersey, 07503

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center

    Pekin, Illinois, 61554

  • Pekin Hospital

    Pekin, Illinois, 61554

  • Proctor Hospital

    Peoria, Illinois, 61614

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • Illinois Valley Hospital

    Peru, Illinois, 61354

  • University of Pennsylvania/Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Ascension Via Christi - Pittsburg

    Pittsburg, Kansas, 66762

  • Michiana Hematology Oncology PC-Plymouth

    Plymouth, Indiana, 46563

  • Pottstown Hospital

    Pottstown, Pennsylvania, 19464

  • Kansas City NCI Community Oncology Research Program

    Prairie Village, Kansas, 66208

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Perry Memorial Hospital

    Princeton, Illinois, 61356

  • Annie Penn Memorial Hospital

    Reidsville, North Carolina, 27320

  • Ascension Saint Mary's Hospital

    Rhinelander, Wisconsin, 54501

  • Saint Mary's Hospital

    Rhinelander, Wisconsin, 54501

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • Reid Health

    Richmond, Indiana, 47374

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Swedish American Hospital

    Rockford, Illinois, 61104

  • OSF Saint Anthony Medical Center

    Rockford, Illinois, 61108

  • Unspecified Site

    Rockville, Maryland, 20852

  • Norris Cotton Cancer Center-North

    Saint Johnsbury, Vermont, 05819

  • Lakeland Medical Center Saint Joseph

    Saint Joseph, Michigan, 49085

  • Marie Yeager Cancer Center

    Saint Joseph, Michigan, 49085

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Saint Joseph Oncology Inc

    Saint Joseph, Missouri, 64507

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Salina Regional Health Center

    Salina, Kansas, 67401

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Prisma Health Cancer Institute - Seneca

    Seneca, South Carolina, 29672

  • Saint Francis Regional Medical Center

    Shakopee, Minnesota, 55379

  • Advent Health - Shawnee Mission Medical Center

    Shawnee Mission, Kansas, 66204

  • HSHS Saint Nicholas Hospital

    Sheboygan, Wisconsin, 53081

  • Welch Cancer Center

    Sheridan, Wyoming, 82801

  • Siouxland Regional Cancer Center

    Sioux City, Iowa, 51101

  • Mercy Medical Center-Sioux City

    Sioux City, Iowa, 51102

  • Saint Luke's Regional Medical Center

    Sioux City, Iowa, 51104

  • Hematology Oncology Associates of Illinois - Skokie

    Skokie, Illinois, 60076

  • Memorial Hospital of South Bend

    South Bend, Indiana, 46601

  • Michiana Hematology Oncology PC-South Bend

    South Bend, Indiana, 46601

Other trials in United States

Canada9 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • CSSS Champlain-Charles Le Moyne

    Greenfield Park, Quebec, J4V 2H1

  • QEII Health Sciences Centre/Nova Scotia Health Authority

    Halifax, Nova Scotia, B3H 2Y9

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • McGill University Health Centre at Royal Victoria Hospital

    Montreal, Quebec, H3A 1A1

  • CHU de Quebec-Hopital du Saint-Sacrement (HSS)

    Québec, Quebec, G1S 4L8

  • University Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Genetic Risk-Stratified, Randomized Phase II Study of Four Fludarabine/Antibody Combinations for Patients With Symptomatic, Previously Untreated Chronic Lymphocytic Leukemia

This randomized phase II trial studies how well fludarabine (fludarabine phosphate) and rituximab with or without lenalidomide or cyclophosphamide work in treating patients with symptomatic chronic lymphocytic leukemia. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Giving fludarabine phosphate and rituximab together with lenalidomide or cyclophosphamide may be an effective treatment for chronic lymphocytic leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the two-year progression-free survival (PFS) after remission induction with four different chemo-immunotherapy combinations for patients with untreated, symptomatic, lower-risk and high-risk chronic lymphocytic leukemia (CLL) to decide which of the four arms, if any, to take forward into a randomized phase III trial.

II. To determine the induction response to fludarabine phosphate and rituximab (FR) and fludarabine phosphate, cyclophosphamide, and rituximab (FCR) in each of these arms, along with the consolidation response to lenalidomide in patients with CLL.

III. To determine the toxicity from these four chemoimmunotherapy combinations and that of consolidation therapy with lenalidomide.

IV. To determine the induction response and toxicity of FCR in patients with deletion (del) (11q22.3) along with consolidation response, 2-year PFS and toxicity of lenalidomide in this specific genetic group.

  1. To determine the effect of pretreatment biologic characteristics on clinical outcomes, such as attaining a complete response to induction therapy and progression-free survival.

VI. To collect relapse samples to determine the frequency of clonal evolution among patients with immunoglobulin heavy chain variable region (IgVH) mutated and unmutated disease and to study mechanisms of resistance to chemoimmunotherapy.

VII. To determine if flow cytometry-negative status immediately post-therapy and at 24 months after study entry is an effective surrogate marker for prolonged progression-free survival and overall survival.

OUTLINE: Patients are randomized to 1 of 3 treatment arms (Arms A, B, or C). Patients on Arm A or B who are found to be del (11q22.3) positive are assigned to Arm D beginning with course 2 of induction therapy.

ARM A (remission-induction [RI] therapy with fludarabine phosphate and rituximab): Participants receive induction therapy (every 28 days for up to 6 cycles) of: rituximab intravenously (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 orally (PO) on days 1-5.

ARM B (RI therapy with fludarabine phosphate and rituximab followed by remission-consolidation [RC] therapy with lenalidomide): 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 once daily (QD) on days 1-21 of 28 day cycle.

ARM C (RI therapy with fludarabine phosphate, rituximab, and cyclophosphamide): 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.

ARM D (RI therapy with fludarabine phosphate, rituximab, and cyclophosphamide followed by RC therapy with lenalidomide): 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 2-6 PO QD on days 1-21 of 28 day cycle.

After completion of study therapy, patients are followed up every 3 months for 1 year and then every 6 months for up to 15 years.

Being tested
Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Lenalidomide, Rituximab
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV or PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT00602459
Study groupRoleWhat they receive
Arm A (rituximab, fludarabine phosphate)Active comparatorParticipants 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.
Receives: Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Rituximab
Arm B (rituximab, fludarabine phosphate, lenalidomide)ExperimentalParticipants 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.
Receives: Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Rituximab
Arm C (rituximab, fludarabine phosphate, cyclophosphamide)ExperimentalParticipants 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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Rituximab
Arm D (rituximab, fludarabine, cyclophosphamide, lenalidomide)ExperimentalPatients 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.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 2-Year Progression Free Survival (PFS) Rate

    Proportion of participants who were alive and progression free at 2 years.

    Measured: 2 years

Secondary outcomes (5)

  1. Overall Response Rate in Patients Without Del(11q22.3)

    Percentage of non-del(11q22.3) participants with a complete response (CR) or partial response (PR). CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus >= 1 of the following: >= 1500/uL polymorphonuclear leukocytes, > 100,000/uL platelets, > 11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions.

    Measured: Up to 15 years

  2. Overall Response Rates in Patients With Del(11q22.3)

    Percentage of del(11q22.3) participants with a complete response (CR) or partial response (PR). CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus >= 1 of the following: >= 1500/uL polymorphonuclear leukocytes, > 100,000/uL platelets, > 11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions.

    Measured: Up to 15 years

  3. PFS Rate of Patients With Del(11q22.3)

    Proportion of del (11q22.3) participants who were alive and progression free at 2 years.

    Measured: 2 years

  4. Time-to-progression in Patients Without Del(11q22.3)

    Time to progression (TTP) was defined as the registration date to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method. Progressive disease (PD) required at least one of the following: >= 50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes, >= 50% increase in the product of at least two lymphnodes, >= 50% increase in the enlargement of the liver and/or spleen.

    Measured: Up to 15 years

  5. Time-to-progression in Patients With Del(11q22.3)

    Time to progression (TTP) in del(11q22.3) participants was defined as the registration date to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method.

    Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2008 (estimated)
  2. Study start15 Jan 2008
  3. Primary completion1 Dec 2014
  4. Study completion15 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
418 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00602459
Sponsor's protocol ID
NCI-2009-00441
Other IDs
NCI-2009-00441, CDR0000584205, ECOG-10404, SWOG-C10404, 11-00126, SWOG C10404, ECOG 10404, CAN-NCIC-CL3
Status last verified
Apr 2023
First submitted
23 Jan 2008
Last updated
22 May 2023

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Stage I Chronic Lymphocytic Leukemia and Stage II Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 364 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 364 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

2-Year Progression Free Survival (PFS) Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00602459.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2023.

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