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ACTIVE NOT RECRUITING

NCT01886872

PHASE3

Rituximab and Bendamustine Hydrochloride, Rituximab and Ibrutinib, or Ibrutinib Alone in Treating Older Patients With Previously Untreated Chronic Lymphocytic Leukemia

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Chemotherapy drugs, such as bendamustine hydrochloride, 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. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether rituximab with bendamustine hydrochloride may work better than rituximab and ibrutinib or ibrutinib alone in treating chronic lymphocytic leukemia.

Official title: A Randomized Phase III Study of Bendamustine Plus Rituximab Versus Ibrutinib Plus Rituximab Versus Ibrutinib Alone in Untreated Older Patients (≥ 65 Years of Age) With Chronic Lymphocytic Leukemia (CLL)

Key Details

Gender

All

Age Range

65 Years - Any

Study Type

INTERVENTIONAL

Enrollment

547

Start Date

2014-01-15

Completion Date

2027-06-24

Last Updated

2026-10-22

Healthy Volunteers

Conditions

Stage I Chronic Lymphocytic Leukemia Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage IV Chronic Lymphocytic Leukemia

Interventions

DRUG

Bendamustine Hydrochloride

Given IV

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration and biopsy

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow aspiration and biopsy

PROCEDURE

Computed Tomography

Undergo CT

DRUG

Ibrutinib

Given PO

OTHER

Laboratory Biomarker Analysis

Correlative studies

OTHER

Quality-of-Life Assessment

Ancillary studies

BIOLOGICAL

Rituximab

Given IV

Inclusion Criteria: * PRE-REGISTRATION (STEP 0) * All patients are REQUIRED to be pre-registered to A041202 in order to submit peripheral blood to the Alliance Hematologic Malignancy Biorepository (HEME) for central Zap-70 methylation. This specimen submission is mandatory prior to registration as results will be used for stratification * REGISTRATION (STEP 1) * Patients must be diagnosed with CLL in accordance with International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria that includes all of the following: * \>= 5 x 10\^9 B lymphocytes (5000/uL) in the peripheral blood * On morphologic review, the leukemic cells must be small mature lymphocytes, and prolymphocytes must not exceed 55% of the blood lymphocytes * CLL cells on immunophenotype (performed locally) must reveal a clonal B-cell population, which express the B cell surface markers of CD19 and CD20, as well as the T-cell antigen CD5; patients with bright surface immunoglobulin expression or lack of CD23 expression in \> 10% of cells must lack t(11;14) translocation by interphase cytogenetics * Patients must be intermediate or high-risk Rai stage CLL * Intermediate risk (formerly Rai stage I/II) is defined by lymphocytosis plus enlarged lymph nodes at any site, with or without hepatomegaly or splenomegaly * High risk (formerly Rai stage III/IV) is defined by lymphocytosis with or without enlarged nodes and spleen plus disease-related anemia (hemoglobin \< 11 g/dL) or thrombocytopenia (platelet count \< 100 x 10\^9/L) that is not attributable to autoimmune hemolytic anemia or thrombocytopenia * Patients must meet criteria for treatment as defined by IWCLL 2008 guidelines which includes at least one of the following criteria: * Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia (not attributable to autoimmune hemolytic anemia or thrombocytopenia) * Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly * Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy * Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy * Constitutional symptoms, which include any of the following: * Unintentional weight loss of 10% or more within 6 months * Significant fatigue * Fevers \> 100.5 degrees F for 2 weeks or more without evidence of infection * Night sweats \> 1 month without evidence of infection * Prior treatment * Patients must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids) * Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment; palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration * Age \>= 65 years * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Patients with active hepatitis B defined by hepatitis B surface antigen positivity or core antibody positivity in the presence of hepatitis B DNA are not eligible for this study; patients with a positive hepatitis B core antibody but with negative hepatitis B DNA may participate, but must have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician * Intravenous immunoglobulin (IVIG) can cause a false positive hepatitis B serology; if patients receiving routine IVIG have core antibody or surface antigen positivity without evidence of active viremia (negative hepatitis B DNA) they may still participate in the study, but should have hepatitis serologies and hepatitis B DNA monitored periodically by the treating physician * Patients must not be receiving active systemic anticoagulation with heparin or warfarin; patients must be off warfarin therapy for at least 30 days prior to enrollment * Patients with class III or class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible * Patients who have had a myocardial infarction, intracranial bleed, or stroke within the past 6 months are not eligible * Patients with known human immunodeficiency virus (HIV) are eligible if their CD4 count is \>= 350 cells/mm\^3 and if they are not taking prohibited CYP-interacting medications * Patients must not have any history of Richter's transformation or prolymphocytic leukemia (prolymphocytes in blood \> 55%) * Patients must not require more than 20 mg prednisone or equivalent corticosteroid daily * Patients must not have uncontrolled active systemic infection requiring intravenous antibiotics * Patients must not have continued requirement for therapy with a strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitor or inducer * Patients must not have a known allergy to mannitol * Patients must not have prior significant hypersensitivity to rituximab (not including infusion reactions) * Patients may not have had major surgery within 10 days of enrollment, or minor surgery within 7 days of enrollment; examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint; the decision about whether a surgery is major or minor can be made at the discretion of the treating physician * Absolute neutrophil count (ANC) \>= 1,000/uL unless due to bone marrow involvement * Aspartate aminotransferase (AST) or alanine aminotransferase (AST) =\< 2.5 x upper limits of normal except if due to disease infiltration of the liver * Bilirubin =\< 1.5 x upper limits of normal (unless due to liver involvement, hemolysis, or Gilbert's disease) * Creatinine clearance \>= 40 mL/min * To be calculated by modified Cockcroft-Gault formula * Platelet count (untransfused) \>= 30,000/uL

Locations (937)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Anchorage Radiation Therapy Center

Anchorage, Alaska, United States

Alaska Breast Care and Surgery LLC

Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC

Anchorage, Alaska, United States

Alaska Regional Hospital

Anchorage, Alaska, United States

Alaska Women's Cancer Care

Anchorage, Alaska, United States

Anchorage Oncology Centre

Anchorage, Alaska, United States

Katmai Oncology Group

Anchorage, Alaska, United States

Providence Alaska Medical Center

Anchorage, Alaska, United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States

Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Banner University Medical Center - Tucson

Tucson, Arizona, United States

University of Arizona Cancer Center-North Campus

Tucson, Arizona, United States

Onvida Health Yuma Medical Center

Yuma, Arizona, United States

CHI Saint Vincent Cancer Center Hot Springs

Hot Springs, Arkansas, United States

NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro

Jonesboro, Arkansas, United States

Kaiser Permanente-Anaheim

Anaheim, California, United States

Kaiser Permanente-Deer Valley Medical Center

Antioch, California, United States

PCR Oncology

Arroyo Grande, California, United States

Sutter Auburn Faith Hospital

Auburn, California, United States

Sutter Cancer Centers Radiation Oncology Services-Auburn

Auburn, California, United States

Kaiser Permanente-Baldwin Park

Baldwin Park, California, United States

Kaiser Permanente-Bellflower

Bellflower, California, United States

Alta Bates Summit Medical Center-Herrick Campus

Berkeley, California, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Mills-Peninsula Medical Center

Burlingame, California, United States

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

Cameron Park, California, United States

John Muir Medical Center-Concord

Concord, California, United States

Sutter Davis Hospital

Davis, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Kaiser Permanente-Fontana

Fontana, California, United States

Kaiser Permanente-Fremont

Fremont, California, United States

Kaiser Permanente-Fresno

Fresno, California, United States

Marin Cancer Care Inc

Greenbrae, California, United States

Marin General Hospital

Greenbrae, California, United States

Kaiser Permanente South Bay

Harbor City, California, United States

Kaiser Permanente-Irvine

Irvine, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Kaiser Permanente West Los Angeles

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Memorial Medical Center

Modesto, California, United States

Kaiser Permanente-Modesto

Modesto, California, United States

Palo Alto Medical Foundation-Camino Division

Mountain View, California, United States

Palo Alto Medical Foundation-Gynecologic Oncology

Mountain View, California, United States

Sutter Cancer Research Consortium

Novato, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Palo Alto Medical Foundation Health Care

Palo Alto, California, United States

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Kaiser Permanente - Panorama City

Panorama City, California, United States

Kaiser Permanente-Redwood City

Redwood City, California, United States

Kaiser Permanente-Richmond

Richmond, California, United States

Kaiser Permanente-Riverside

Riverside, California, United States

Kaiser Permanente-Roseville

Roseville, California, United States

Sutter Cancer Centers Radiation Oncology Services-Roseville

Roseville, California, United States

Sutter Roseville Medical Center

Roseville, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

Kaiser Permanente Sacramento Medical Center

Sacramento, California, United States

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Naval Medical Center -San Diego

San Diego, California, United States

California Pacific Medical Center-Pacific Campus

San Francisco, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, United States

Stanford Cancer Center South Bay

San Jose, California, United States

Kaiser Permanente San Leandro

San Leandro, California, United States

Kaiser Permanente-San Marcos

San Marcos, California, United States

Kaiser Permanente-San Rafael

San Rafael, California, United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, United States

Palo Alto Medical Foundation-Santa Cruz

Santa Cruz, California, United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California, United States

Sutter Pacific Medical Foundation

Santa Rosa, California, United States

Kaiser Permanente-South San Francisco

South San Francisco, California, United States

Saint Helena Hospital

St. Helena, California, United States

Kaiser Permanente-Stockton

Stockton, California, United States

Palo Alto Medical Foundation-Sunnyvale

Sunnyvale, California, United States

Northbay Cancer Center

Vacaville, California, United States

Kaiser Permanente Medical Center-Vacaville

Vacaville, California, United States

Kaiser Permanente-Vallejo

Vallejo, California, United States

Sutter Solano Medical Center/Cancer Center

Vallejo, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States

Presbyterian Intercommunity Hospital

Whittier, California, United States

Kaiser Permanente-Woodland Hills

Woodland Hills, California, United States

Rocky Mountain Cancer Centers-Aurora

Aurora, Colorado, United States

The Medical Center of Aurora

Aurora, Colorado, United States

Boulder Community Foothills Hospital

Boulder, Colorado, United States

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

Denver Health Medical Center