Early or Delayed Fludarabine and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

Leukemia Clinical Trial

Official title:

A Phase III Intergroup CLL Study of Asymptomatic Patients With Untreated Chronic Lymphocytic Leukemia Randomized to Early Intervention Versus Observation With Later Treatment in the High Risk Genetic Subset With IGVH Unmutated Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00513747
• Other study ID #: CALGB-10501
• Secondary ID: U10CA031946CDR00
• Status: Terminated
• Phase: Phase 3
• Start date: January 2008
• Est. completion date: June 2016

Study information

• Verified date: April 2020
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fludarabine together with rituximab may kill more cancer cells. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving fludarabine together with rituximab early is more effective than giving fludarabine and rituximab after observation in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying fludarabine and rituximab to compare how well they work when given early or after observation in treating patients with previously untreated chronic lymphocytic leukemia.

Description:

OBJECTIVES:

Primary

• To determine if early treatment with chemoimmunotherapy comprising fludarabine phosphate and rituximab extends the time to second treatment in patients with genetically high-risk (unmutated IgV_H), asymptomatic, previously untreated chronic lymphocytic leukemia (CLL).

• To determine the time to disease progression that would warrant second treatment.

• To determine overall survival.

Secondary

• To measure the proportion of patients with asymptomatic, previously untreated CLL who have mutated and unmutated IgV_H genes.

• To determine the differences in acute and chronic toxicity of administering chemoimmunotherapy early to patients with genetically high-risk CLL compared to waiting until symptoms develop.

• To determine the effect of select pretreatment clinical and biological characteristics (such as interphase cytogenetic abnormalities, ZAP-70 expression, and p53 dysfunction [primary and secondary]) on response, time to second treatment, and overall survival of patients with genetically high-risk CLL randomized to early treatment.

• To determine the effect of select pretreatment clinical and biological characteristics (such as interphase cytogenetic abnormalities, ZAP-70 expression, and p53 dysfunction) on response, time to first and second treatments, and overall survival of patients with genetically high-risk CLL randomized to standard treatment (observation until symptoms occur).

• To describe the natural history of patients with genetically low-risk (mutated IgV_H genes), asymptomatic, previously untreated CLL, in terms of time to initial treatment, response, progression, and survival.

• To determine the effect of select pretreatment characteristics on time to first treatment, response, progression, and survival of patients with genetically low-risk CLL.

• To correlate patterns of resistance that emerge in patients with unmutated IgV_H genes who have relapsing or refractory CLL following receipt of chemoimmunotherapy with clonal evolution, including acquisition of high-risk karyotype abnormalities, p53 mutations, p53 dysfunction (primary and secondary), altered mRNA and protein expression related to treatment resistance, DNA mutations, microRNA gene expression, and methylation changes.

• To determine whether highly sensitive flow cytometry negativity at completion of therapy in patients randomized to early treatment is an effective surrogate marker for prolonged time to second treatment, overall survival, and other clinical benefits.

• To collect demographic data on familial CLL in newly diagnosed patients participating on this study.

OUTLINE: This is a multicenter study.

• Genetically high-risk disease: Patients are stratified according to age (< 50 years vs 50 to 70 years vs > 70 years) and presence of the high-risk genetic feature [del(11)(q22.3) or del(17)(p13.1)] by FISH (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive rituximab IV over 4 hours on days 1, 3, and 5 of week 1 and then on day 1 of weeks 5, 9, 13, 17, and 21. Patients also receive fludarabine phosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.

• Arm II: Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in arm I. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.

• Genetically low-risk disease: Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in arm I. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.

Patients undergo blood sample collection periodically for correlative studies.

After finishing treatment, patients are followed periodically.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 84
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Eligibility Criteria for Pre-Registration:

1. Patients must be within 6 months of the initial flow cytometric confirmation of B-cell chronic lymphocytic leukemia (CLL). This interval begins with the initial flow cytometric confirmation of disease.

2. Clinical and immunophenotypic evidence of CLL including:

2.1 An absolute lymphocytosis of > 5,000/µL

• Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes.

• Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers.

• Additionally, the B-cells must be monoclonal with regard to expression of either ? or ? and have surface immunoglobulin expression of low density.

• Patients with bright surface immunoglobulin levels must have CD23 coexpression and absence of t(11;14) on interphase cytogenetics or have negative tumor protein staining for cyclin D1.

2.2 Staging - Patients must be in the low category (i.e., only stages 0 or I) of the modified three-stage Rai staging system as described in the protocol.

3. Patients should not have evidence of active disease as demonstrated by any of the following criteria:

• Splenomegaly and/or massive/progressive lymphadenopathy that would require therapy

• Presence of weight loss > 10% over the preceding 6 month period

• Grade 2 or 3 fatigue

• Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of infection

• Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.

4. Prior Treatment: No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL.

5. Age = 18 years

6. Performance Status 0 - 1.

7. No HIV disease. Due to alterations in host immunity, patients known to have HIV infection may not be enrolled.

8. Non-pregnant and non-nursing. Due to the unknown teratogenic potential of chemotherapy, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.

9. Required Initial Laboratory Values:

• Creatinine = 1.5 x upper limit of normal

Eligibility Criteria for Registration (to Low-Risk Cohort or High-Risk Cohort Randomization between Early Intervention Versus Observation with Later Treatment)

1. Successful determination of IgVH mutational status by reference laboratory.

2. Absence of progression of CLL, i.e., absence of the following:

• Progressive splenomegaly and/or lymphadenopathy on two independent measures spaced two weeks apart. If one assessment notes progression, this should be repeated prior to re-registration.

• Development of anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/µL).

• Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.

• Symptoms referable to CLL, including weight loss > 10% over the preceding 6 month period; grade 2 or 3 fatigue; or fevers > 100.5°F and/or night sweats for greater than 2 weeks without evidence of infection.

3. Required Laboratory Value:

• Creatinine = 1.5 x upper limit of normal

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• rituximab
Given IV over 4 hours

Drug:
• fludarabine phosphate
Given IV over 30 minutes

Locations

Country	Name	City	State
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	Moncton Hospital	Moncton	New Brunswick
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Northeastern Ontario Regional Cancer Centre	Sudbury	Ontario
Canada	Edmond Odette Cancer Centre at Sunnybrook	Toronto	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Phoebe Cancer Center at Phoebe Putney Memorial Hospital	Albany	Georgia
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	McFarland Clinic, PC	Ames	Iowa
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Regional Medical Center	Anniston	Alabama
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medical Center	Bangor	Maine
United States	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Mountainview Medical	Berlin	Vermont
United States	Hematology Oncology Associates of Illinois - Berwyn	Berwyn	Illinois
United States	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Bismarck Cancer Center	Bismarck	North Dakota
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Mid Dakota Clinic, PC	Bismarck	North Dakota
United States	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota
United States	Illinois CancerCare - Bloomington	Bloomington	Illinois
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber/Brigham and Women's Cancer Center	Boston	Massachusetts
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Wood County Oncology Center	Bowling Green	Ohio
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Lahey Clinic Medical Center - Burlington	Burlington	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Illinois CancerCare - Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare - Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa
United States	North Coast Cancer Care - Clyde	Clyde	Ohio
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Medical Center Cancer Care	Columbus	Ohio
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Mount Carmel Health - West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Batte Cancer Center at Northeast Medical Center	Concord	North Carolina
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Grady Memorial Hospital	Delaware	Ohio
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mercy Capitol Hospital	Des Moines	Iowa
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Union Hospital Cancer Program at Union Hospital	Elkton	Maryland
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Hematology Oncology Center	Elyria	Ohio
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan
United States	Eureka Community Hospital	Eureka	Illinois
United States	Illinois CancerCare - Eureka	Eureka	Illinois
United States	Blanchard Valley Medical Associates	Findlay	Ohio
United States	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Central Wisconsin Cancer Program at Agnesian HealthCare	Fond Du Lac	Wisconsin
United States	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Sparks Regional Medical Center	Fort Smith	Arkansas
United States	Middletown Regional Hospital	Franklin	Ohio
United States	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Virginia K. Crosson Cancer Center at St. Jude Medical Center	Fullerton	California
United States	Galesburg Clinic, PC	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare - Galesburg	Galesburg	Illinois
United States	Oncology Alliance, SC - Milwaukee - East	Glendale	Wisconsin
United States	Adirondack Cancer Care - Glens Falls	Glens Falls	New York
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin
United States	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	CCOP - Greenville	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Illinois CancerCare - Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Northern Montana Hospital	Havre	Montana
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	St. Peter's Hospital	Helena	Montana
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Kellogg Cancer Care Center	Highland Park	Illinois
United States	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Veterans Affairs Medical Center - Iowa City	Iowa City	Iowa
United States	Dickinson County Healthcare System	Iron Mountain	Michigan
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Midwest Center for Hematology/Oncology	Joliet	Illinois
United States	Ella Milbank Foshay Cancer Center at 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 at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CCOP - Kansas City	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Parvin Radiation Oncology	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	St. Joseph Medical Center	Kansas City	Missouri
United States	Truman Medical Center - Hospital Hill	Kansas City	Missouri
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Monter Cancer Center of the North Shore-LIJ Health System	Lake Success	New York
United States	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware
United States	Southwest Medical Center	Liberal	Kansas
United States	Liberty Hospital	Liberty	Missouri
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	Lima Memorial Hospital	Lima	Ohio
United States	St. Rita's Medical Center	Lima	Ohio
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Illinois CancerCare - Macomb	Macomb	Illinois
United States	McDonough District Hospital	Macomb	Illinois
United States	Manchester Memorial Hospital	Manchester	Connecticut
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York
United States	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Northwest Ohio Oncology Center	Maumee	Ohio
United States	St. Luke's Hospital	Maumee	Ohio
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois
United States	Illinois CancerCare - Monmouth	Monmouth	Illinois
United States	OSF Holy Family Medical Center	Monmouth	Illinois
United States	Community Cancer Center of Monroe	Monroe	Michigan
United States	Mercy Memorial Hospital - Monroe	Monroe	Michigan
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Camino Medical Group - Treatment Center	Mountain View	California
United States	Community Hospital	Munster	Indiana
United States	Edward Hospital Cancer Center	Naperville	Illinois
United States	La Grange Oncology Associates - Geneva	Naperville	Illinois
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Illinois CancerCare - Community Cancer Center	Normal	Illinois
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin
United States	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Immanuel Medical Center	Omaha	Nebraska
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Toledo Clinic - Oregon	Oregon	Ohio
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's Hospital - South	Overland Park	Kansas
United States	Palo Alto Medical Foundation	Palo Alto	California
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Memorial Hospital of Rhode Island	Pawtucket	Rhode Island
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare - Pekin	Pekin	Illinois
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	West Florida Cancer Institute at West Florida Hospital - Pensacola	Pensacola	Florida
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare - Peru	Peru	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Joan Karnell Cancer Center at Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Cancer Center at Phoenixville Hospital	Phoenixville	Pennsylvania
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Kaiser Permanente Health Care - Portland	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Illinois CancerCare - Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Reid Hospital & Health Care Services	Richmond	Indiana
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Coborn Cancer Center	Saint Cloud	Minnesota
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Oncology Care Associates, PLLC	Saint Joseph	Michigan
United States	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	New Mexico Cancer Care Associates	Santa Fe	New Mexico
United States	Group Health Central Hospital	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	Illinois CancerCare - Spring Valley	Spring Valley	Illinois
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Mercy Medical Center	Springfield	Ohio
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Geisinger Medical Group - Scenery Park	State College	Pennsylvania
United States	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	North Suburban Medical Center	Thornton	Colorado
United States	Mercy Hospital of Tiffin	Tiffin	Ohio
United States	CCOP - Toledo Community Hospital	Toledo	Ohio
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	St. Vincent Mercy Medical Center	Toledo	Ohio
United States	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Fox Chase Virtua Health Cancer Program at Virtua West Jersey	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	St. John Macomb Hospital	Warren	Michigan
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Cedar Valley Medical Specialists, PC - West Ridgeway Avenue	Waterloo	Iowa
United States	Covenant Cancer Treatment Center	Waterloo	Iowa
United States	MaineGeneral Medical Center - Waterville	Waterville	Maine
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	Fulton County Health Center	Wauseon	Ohio
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Clinton Memorial Hospital	Wilmington	Ohio
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Central Dupage Cancer Center	Winfield	Illinois
United States	Wake Forest University Comprehensive Cancer Center	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	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Second Treatment in High Risk Patients	Kaplan-Meier analysis was conducted to estimate the distribution of time from randomization to second treatment or death whichever comes first. Events were defined as the start of second treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.	Up to 72 months
Primary	Disease-Free Survival in High Risk Patients	Kaplan-Meier analysis was conducted to estimate disease free survival defined as:>; Arm A: Time from randomization until Second Treatment (first relapse) or death whichever comes first. Events were defined as the start of second treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.>; Arm B: Time from randomization until First Treatment (first relapse) or death whichever comes first. Events were defined as the start of first treatment or death. Patients who had not experienced one of these defined events of interest were censored at their last known follow-up.	Up to 72 months
Primary	Overall Survival (OS) for High Risk Patients	Kaplan-Meier analysis was conducted to estimate the distribution of time from randomization to death from any cause. Estimates were not stratified. Patients who did not experience this primary outcome had their survival times censored at their last follow-up.	Up to 72 months
Secondary	Number of Patients With Mutated and Unmutated IgVH Genes	Number of patients with mutated and unmutated IgVH genes are reported below.	Once at baseline
Secondary	Overall Survival in Low Risk Patients	Overall survival in low risk patients (registration to first treatment or death)>; • Events were defined as death from any cause. Low risk Patients who were alive were censored at their last known follow-up.	Up to 72 months
Secondary	Time to First Treatment Survival in Low Risk Patients	Time to First Treatment Survival in low risk patients (registration to first treatment or death)>; • Events were defined as the start of first treatment or death from any cause. Patients who didn't receive their first treatment were censored at their last known follow-up.	Up to 72 months