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

Stage IV Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00602459
• Other study ID #: NCI-2009-00441
• Secondary ID: NCI-2009-00441CD
• Status: Completed
• Phase: Phase 2
• Start date: January 15, 2008
• Est. completion date: April 15, 2023

Study information

• Verified date: April 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Description:

PRIMARY OBJECTIVES: I. 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. V. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 418
• Est. completion date: April 15, 2023
• Est. primary completion date: December 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Stage I Chronic Lymphocytic Leukemia
• Stage II Chronic Lymphocytic Leukemia
• Stage III Chronic Lymphocytic Leukemia
• Stage IV Chronic Lymphocytic Leukemia

Intervention

Drug:
• Cyclophosphamide
Given IV
• Fludarabine Phosphate
Given IV or PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lenalidomide
Given PO

Biological:
• Rituximab
Given IV

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	CSSS Champlain-Charles Le Moyne	Greenfield Park	Quebec
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	McGill University Health Centre at Royal Victoria Hospital	Montreal	Quebec
Canada	CHU de Quebec-Hopital du Saint-Sacrement (HSS)	Quebec City	Quebec
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Lovelace Medical Center-Saint Joseph Square	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Anthony's Health	Alton	Illinois
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	PCR Oncology	Arroyo Grande	California
United States	Randolph Hospital	Asheboro	North Carolina
United States	Mission Hospital	Asheville	North Carolina
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	MacNeal Hospital and Cancer Center	Berwyn	Illinois
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Weiss Memorial Hospital	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Baylor University Medical Center	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Easton Hospital	Easton	Pennsylvania
United States	HSHS Sacred Heart Hospital	Eau Claire	Wisconsin
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Ascension Alexian Brothers - Elk Grove Village	Elk Grove Village	Illinois
United States	Elkhart Clinic	Elkhart	Indiana
United States	Elkhart General Hospital	Elkhart	Indiana
United States	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Self Regional Healthcare	Greenwood	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Hutchinson Regional Medical Center	Hutchinson	Kansas
United States	Centerpoint Medical Center LLC	Independence	Missouri
United States	Iowa City VA Healthcare System	Iowa City	Iowa
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	Midwest Center for Hematology Oncology	Joliet	Illinois
United States	Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Presence Saint Mary's Hospital	Kankakee	Illinois
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Providence Medical Center	Kansas City	Kansas
United States	Radiation Oncology Practice Corporation - North	Kansas City	Missouri
United States	Radiation Oncology Practice Corporation South	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Community Howard Regional Health	Kokomo	Indiana
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	IU Health La Porte Hospital	La Porte	Indiana
United States	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire
United States	Northwell Health NCORP	Lake Success	New York
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Beebe Medical Center	Lewes	Delaware
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	AMG Libertyville - Oncology	Libertyville	Illinois
United States	Doctors Carrol, Sheth, Raghavan	Louisville	Kentucky
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Norris Cotton Cancer Center-Manchester	Manchester	New Hampshire
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	North Shore University Hospital	Manhasset	New York
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Medical Center	Marinette	Wisconsin
United States	Marshfield Medical Center	Marshfield	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Loyola University Medical Center	Maywood	Illinois
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana
United States	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	DuPage Medical Group-Ogden	Naperville	Illinois
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Lakeland Hospital Niles	Niles	Michigan
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Norwalk Hospital	Norwalk	Connecticut
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	Olathe Cancer Center	Olathe	Kansas
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Ottumwa Regional Health Center	Ottumwa	Iowa
United States	Menorah Medical Center	Overland Park	Kansas
United States	Radiation Oncology Practice Corporation Southwest	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana
United States	Pottstown Hospital	Pottstown	Pennsylvania
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Ascension Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	OSF Saint Anthony Medical Center	Rockford	Illinois
United States	Swedish American Hospital	Rockford	Illinois
United States	Unspecified Site	Rockville	Maryland
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Lakeland Medical Center Saint Joseph	Saint Joseph	Michigan
United States	Marie Yeager Cancer Center	Saint Joseph	Michigan
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Comprehensive Cancer Care PC	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	SSM Health Saint Louis University Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Salina Regional Health Center	Salina	Kansas
United States	UCSF Medical Center-Mount Zion	San Francisco	California
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	South Bend Clinic	South Bend	Indiana
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Ascension Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Carle Cancer Center	Urbana	Illinois
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Michiana Hematology Oncology PC-Westville	Westville	Indiana
United States	Wheeling Hospital/Schiffler Cancer Center	Wheeling	West Virginia
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger South Wilkes-Barre	Wilkes-Barre	Pennsylvania
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Eastern Cooperative Oncology Group, NCIC Clinical Trials Group, SWOG Cancer Research Network

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2-Year Progression Free Survival (PFS) Rate	Proportion of participants who were alive and progression free at 2 years.	2 years
Secondary	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.	Up to 15 years
Secondary	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.	Up to 15 years
Secondary	PFS Rate of Patients With Del(11q22.3)	Proportion of del (11q22.3) participants who were alive and progression free at 2 years.	2 years
Secondary	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.	Up to 15 years
Secondary	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.	Up to 15 years