Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma

Lymphoma Clinical Trial

Official title:

A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01216683
• Other study ID #: E2408
• Secondary ID: E2408NCI-2011-02
• Status: Completed
• Phase: Phase 2
• Start date: February 9, 2011
• Est. completion date: December 2, 2019

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride, 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bendamustine hydrochloride and rituximab together alone is more effective than giving bendamustine hydrochloride and rituximab together with bortezomib or lenalidomide in treating follicular lymphoma.

PURPOSE: This randomized phase II trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage II, stage III, or stage IV follicular lymphoma.

Description:

OBJECTIVES:

Primary

• To compare the complete remission rate in patients with high-risk follicular lymphoma receiving induction therapy comprising bendamustine hydrochloride and rituximab with vs without bortezomib.

• To compare the 1-year post-induction disease-free survival rate in patients receiving continuation therapy comprising rituximab with vs without lenalidomide.

Secondary

• To determine the 3-year progression-free survival and the 5-year overall survival of these patients.

• To evaluate patient-reported outcomes at baseline and during treatment to determine differences in symptom palliation, treatment-related symptoms, and overall health-related quality of life.

• To examine the association between baseline Follicular Lymphoma International Prognostic Index (FLIPI) information and outcome of these patients.

• To examine the association between baseline and end-of-treatment patient comorbidities assessed by the Cumulative Illness Rating Scale (CIRS) and outcome.

• To create an image and tissue bank including serial PET/CT scans, diagnostic paraffin-embedded tissue, germline DNA, and serial blood and bone marrow samples sufficient to support proposed and future studies of tumor and host characteristics that may predict for clinical outcome, including treatment arm effects, and enhance existing prognostic indices. (exploratory)

• To evaluate the rate of peripheral neuropathy associated with subcutaneous and intravenous bortezomib.

OUTLINE: Patients are stratified according to FLIPI-1score (0-2 vs 3 vs 4-5) and Groupe d'Etude des Lymphomes Folliculaires (GELF) tumor burden (low vs high). Patients are randomized to 1 of 3 treatment arms.

• Arm A then Arm D

• Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

• Arm B then Arm E

• Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.

• Arm C then Arm F

• Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Quality of life (including fatigue, neurotoxicity, anxiety, and depression) is assessed by questionnaire at baseline and periodically during study therapy.

Blood, bone marrow, and tissue samples may be collected periodically for correlative studies and for a repository.

After completion of study therapy, patients are followed up periodically for 15 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 289
• Est. completion date: December 2, 2019
• Est. primary completion date: December 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (Induction):

• Histologically confirmed (biopsy-proven) diagnosis of follicular B-cell non-Hodgkin lymphoma with no evidence of transformation to large cell histology

• Patients having both diffuse and follicular architectural elements are eligible if the histology is predominantly follicular (i.e., = 50% of the cross-sectional area) and there is no evidence of transformation to a large cell histology

• Diagnostic confirmation (i.e., core needle or excisional lymph node biopsy) required if the interval since tissue diagnosis of low-grade malignant lymphoma is > 24 months

• Bone marrow biopsy alone not acceptable

• Stage II, III, or IV AND grade 1, 2, or 3a disease

• Must meet criteria for High Tumor Burden (higher risk) as defined by either the Groupe D'Etude des Lymphomes Follicularies (GELF) criteria OR the follicular lymphoma international prognostic index (FLIPI) as defined below:

• Patient must meet = 1 of the following GELF criteria:

• Nodal or extranodal mass = 7 cm

• At least 3 nodal masses > 3.0 cm in diameter

• Systemic symptoms due to lymphoma or B symptoms

• Splenomegaly with spleen > 16 cm by CT scan

• Evidence of compression syndrome (e.g., ureteral, orbital, gastrointestinal) or pleural or peritoneal serous effusion due to lymphoma (irrespective of cell content)

• Leukemic presentation (= 5.0 x 10^9/L malignant circulating follicular cells)

• Cytopenias (polymorphonuclear leukocytes < 1.0 X 10^9/L, hemoglobin < 10 g/dL, and/or platelets < 100 x 10^9/L)

• Patient must have a FLIPI-1 score of 3, 4, or 5 (1 point per criterion below):

• Age = 60 years

• Stage III-IV disease

• Hemoglobin level < 12 g/dL

• > 4 nodal areas

• Serum lactate dehydrogenase (LDH) level above normal

• At least 1 objective measurable disease parameter

• Baseline measurements and evaluations (PET and CT) obtained within 6 weeks of randomization

• Measurable disease in the liver is required if the liver is the only site of lymphoma

• HIV-positive patients must meet all of the following criteria:

• HIV is sensitive to antiretroviral therapy

• Must be willing to take effective antiretroviral therapy if indicated

• No history of CD4 < 300 cells/mm³ prior to or at the time of lymphoma diagnosis

• No history of AIDS-defining conditions

• If on antiretroviral therapy, must not be taking zidovudine or stavudine

• Must be willing to take prophylaxis for Pneumocystis jiroveci pneumonia (PCP) during therapy and = 2 months following completion of study therapy or until the CD4 cells recover to over 250 cells/mm³

• ECOG performance status 0-2

• Absolute neutrophil count (ANC) = 1,500/mm³ (includes neutrophils and bands)

• Platelet count = 100,000/mm³

• Creatinine = 2.0 mg/dL

• Aspartate aminotransferase (AST) and alanine transaminase (ALT) = 5 x upper limit of normal (ULN)

• Alkaline phosphatase = 5 x ULN

• Total bilirubin = 1.5 x ULN (patients with known Gilbert disease should contact the study PI)

• Negative pregnancy test

• Fertile patients must use 2 effective methods (1 highly effective and 1 additional effective method) of contraception = 28 days before, during, and for = 28 days after completing study treatment

• Must register into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist® (for patients randomized to arm C and proceed onto arm F)

Exclusion Criteria (Induction):

• Prior chemotherapy, radiotherapy, or immunotherapy for lymphoma

• Prednisone or other corticosteroids used for non-lymphomatous conditions will not be considered as prior chemotherapy

• A prior/recent short course (< 2 weeks) of steroids for symptom relief of lymphoma-related symptoms is allowed

• Recent history of malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for = 2 years

• Pregnant or nursing

• Active, uncontrolled infections (afebrile for > 48 hours off antibiotics)

• = grade 2 neuropathy

• Myocardial infarction within the past 6 months

• NYHA class III-IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study

• Known hypersensitivity to boron or mannitol

• Chronic carriers of hepatitis B virus (HBV) with positive hepatitis surface antigen (HBsAg +)

Inclusion Criteria (Continuation):

• Patient must have improved their response or have had no interval change in their tumor measurements with restaging from Induction cycle 3 to 6 as determined at Cycle 6 restaging.

• Adequate organ function

• ECOG performance status 0-2

• Patients with a prior history of HBV infection, but immune, with only IgG hepatitis core antibody positive (HBcAb+), must receive antiviral prophylaxis (e.g., lamivudine 100 mg po daily) for = 1 week prior to course 1 and throughout induction and continuation therapy and for = 12 months after the last rituximab dose

• Additional requirements for Arm C induction patients registering to arm F:

• Patients must be willing to take deep vein thrombosis (DVT) prophylaxis. Subjects with a history of a thrombotic vascular event will be required to have full anticoagulation, therapeutic doses of low molecular weight heparin or warfarin to maintain an INR between 2.0 - 3.0, or any other accepted full anticoagulation regimen (e.g. direct thrombin inhibitors or Factor Xa inhibitors) with appropriate monitoring for that agent. Subjects without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis. Subjects who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment or another accepted full anticoagulation regimen.

• Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study/lenalidomide: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study; and 3) for at least 28 days after discontinuation/stopping lenalidomide. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.

• Patient must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment.

• All males, regardless of whether they have undergone a successful vasectomy, must agree to use a latex condom during sexual contact with a female of childbearing potential, or to practice complete abstinence from heterosexual intercourse with any female of childbearing potential during the cycles of continuation therapy of which lenalidomide are taken and for at least 28 days after discontinuation/stopping lenalidomide. Patient must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from protocol treatment.

• Must register into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist®

Exclusion Criteria (Continuation):

• Active, uncontrolled infections (afebrile for > 48 hours off antibiotics)

• = grade 2 neuropathy

• Additional requirements for Arm C induction patients registering to arm F:

• Not pregnant or breast-feeding

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• rituximab
Given IV

Drug:
• Bendamustin
Given IV
• bortezomib
Given IV
• lenalidomide
Given orally

Locations

Country	Name	City	State
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio
United States	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	Fox Valley Hematology and Oncology	Appleton	Wisconsin
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia
United States	Georgia Regents University Medical Center	Augusta	Georgia
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	The Medical Center of Aurora	Aurora	Colorado
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Ochsner Health Center-Summa	Baton Rouge	Louisiana
United States	Sanford Clinic North-Bemidgi	Bemidji	Minnesota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Dana-Farber Harvard Cancer Center	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Boulder Community Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio
United States	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Mercy Medical Center	Canton	Ohio
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Geaugra Hospital	Chardon	Ohio
United States	West Virginia University Charleston	Charleston	West Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
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	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Parkland Memorial Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Carle on Vermilion	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Colorado Cancer Research Program CCOP	Denver	Colorado
United States	Exempla Saint Joseph Hospital	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota
United States	Miller-Dwan Hospital	Duluth	Minnesota
United States	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey
United States	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin
United States	Fairview-Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Comprehensive Cancer Care and Research Institute of Colorado LLC	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	Green Bay Oncology - Escanaba	Escanaba	Michigan
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota
United States	Roger Maris Cancer Center	Fargo	North Dakota
United States	Sanford Clinic North-Fargo	Fargo	North Dakota
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Vanderbilt-Ingram Cancer Center Cool Springs	Franklin	Tennessee
United States	Unity Hospital	Fridley	Minnesota
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Bellin Memorial Hospital	Green Bay	Wisconsin
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 Mary's Hospital	Green Bay	Wisconsin
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	Marin Cancer Care Inc	Greenbrae	California
United States	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado
United States	Cancer Institute of New Jersey At Hamilton	Hamilton	New Jersey
United States	Mason District Hospital	Havana	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan
United States	Allegiance Health	Jackson	Michigan
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	IU Health Arnett Cancer Care	Lafayette	Indiana
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Geisinger Medical Oncology at Evangelical Community Hospital	Lewisburg	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	North Shore Hematology Oncology	Libertyville	Illinois
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	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	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Vince Lombardi Cancer Clinic-Marinette	Marinette	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Ireland Cancer Center Landerbrook Health Center	Mayfield Heights	Ohio
United States	Lake University Ireland Cancer Center	Mentor	Ohio
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Ochsner Baptist Medical Center	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	New York University Langone Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	UMDNJ - New Jersey Medical School	Newark	New Jersey
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center Foundation	Normal	Illinois
United States	Oconomowoc Memorial Hospital-ProHealth Care Inc	Oconomowoc	Wisconsin
United States	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin
United States	UHHS-Chagrin Highlands Medical Center	Orange Village	Ohio
United States	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
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	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	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	Aria Health-Torresdale Campus	Philadelphia	Pennsylvania
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Saint Joseph Mercy Oakland	Pontiac	Michigan
United States	Geisinger Medical Oncology-Pottsville	Pottsville	Pennsylvania
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin
United States	Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic	Rochester	Minnesota
United States	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois
United States	Saint Mary's of Michigan	Saginaw	Michigan
United States	Metro-Minnesota CCOP	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	Salinas Valley Memorial	Salinas	California
United States	Ireland Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Hematology Oncology Associates	Sioux City	Iowa
United States	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Memorial Medical Center	Springfield	Illinois
United States	Stanford University Hospitals and Clinics	Stanford	California
United States	Geisinger Medical Group	State College	Pennsylvania
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Flower Hospital	Sylvania	Ohio
United States	North Suburban Medical Center	Thornton	Colorado
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio
United States	Vince Lombardi Cancer Clinic	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Waukesha Memorial Hospital - ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Reading Hospital	West Reading	Pennsylvania
United States	UH-Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Diagnostic and Treatment Center	Weston	Wisconsin
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Wesley Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Evens AM, Hong F, Habermann TM, Advani RH, Gascoyne RD, Witzig TE, Quon A, Ranheim EA, Ansell SM, Cheema PS, Dy PA, O'Brien TE, Winter JN, Cescon TP, Chang JE, Kahl BS. A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induct — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Remission (CR) Rate	Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.; This analysis was conducted among 222 evaluable patients for the primary analysis. The purpose of this analysis is to compare the complete remission rate of rituximab + bendamustine vs. bortezomib + rituximab + bendamustine as induction therapy, therefore, the proportion of patients with complete remission was compared between Arm B (bortezomib + rituximab + bendamustine) and Arms A and C combined (rituximab + bendamustine).	Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years
Primary	1-year Post-induction Disease-free Survival (DFS) Rate	1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.; The purpose of this analysis is to compare the 1-year post-induction disease-free survival (DFS) rate with rituximab plus lenalidomide to rituximab alone as continuation therapy following induction treatment of bendamustine+rituximab, therefore, patients with induction treatment of bendamustine + rituximab + bortezomib were not included in this analysis.	Assessed at 1 year post-induction, approximately 1.5 years
Secondary	3-year Progression-free Survival Rate	Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. 3-year progression-free survival rate is the proportion of patients who were progression-free and alive at 3 years estimated using the method of Kaplan-Meier.; Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, >=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.	Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
Secondary	5-year Overall Survival Rate	Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.	Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
Secondary	Complete Remission (CR) Rate	Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.; This analysis was conducted among 222 evaluable patients. The proportion of patients with complete remission was compared between patients with Follicular Lymphoma International Prognostic Index (FLIPI) of 3-5 and patients with FLIPI of 0-2/unknown.; The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.	Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years
Secondary	1-year Disease-free Survival (DFS) Rate	1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.; This analysis was conducted among 203 evaluable patients in the continuation treatment portion of the study. The 1-year post induction disease-free survival rate was compared between patients with FLIPI of 3-5 and patients with FLIPI of 0-2/unknown.; The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.	Assessed at 1 year post-induction, approximately 1.5 years
Secondary	Progression-free Survival	Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, >=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.; The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.	Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
Secondary	5-year Overall Survival Rate	Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.; The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age > 60 years, Ann Arbor stage III-IV, hemoglobin level < 12 gm/dL, >4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.	Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
Secondary	Complete Remission (CR) Rate	Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.; This analysis was conducted among 250 evaluable patients with Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients with complete remission was compared between patients with CIRS <10 and patients with CIRS >=10. Higher CIRS scores indicate higher severity with max score of 56 points.	Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years
Secondary	1-year Disease-free Survival (DFS) Rate	1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.; This analysis was conducted among 250 evaluable patients with Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients disease-free and alive at 1 year post induction treatment was compared between patients with CIRS <10 and patients with CIRS >=10. Higher CIRS scores indicate higher severity with max score of 56 points.	Assessed at 1 year post-induction, approximately 1.5 years
Secondary	3-year Progression-free Survival Rate	Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. 3-year progression-free survival rate is the proportion of patients who were progression-free and alive at 3 years estimated using the method of Kaplan-Meier.; Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, >=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.; The 3-year progression-free survival rate is reported by Cumulative Illness Rating Scale (CIRS) score (<10 vs. >=10). Higher CIRS scores indicate higher severity with max score of 56 points.	Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
Secondary	5-year Overall Survival Rate	Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.; The 5-year overall survival rate is reported by Cumulative Illness Rating Scale (CIRS) score (<10 vs. >=10). Higher CIRS scores indicate higher severity with max score of 56 points.	Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry
Secondary	Proportion of Patients With Grade 3 or Higher Peripheral Neuropathy	Peripheral neuropathy was assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Proportion of patients with grade 3 or higher peripheral neuropathy was compared between patients with subcutaneous bortezomib and patients with intravenous bortezomib.	Assessed every cycle during treatment and for 30 days after discontinuation of treatment, up to 15 years
Secondary	Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Baseline	The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life.	Assessed at baseline
Secondary	Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Mid-treatment	The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life.; FACT-G total score at cycle 3 is considered as mid-treatment score. If FACT-G total score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.	Assessed at cycle 3 or cycle 4, approximately 3 or 4 months
Secondary	Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at End of Induction Treatment	The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life.	Assessed at cycle 6, approximately 6 months
Secondary	Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Baseline	The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life.	Assessed at baseline
Secondary	Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Mid-induction Treatment	The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life.; FACT-Lym subscale score at cycle 3 is considered as mid-treatment score. If FACT-Lym subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.	Assessed at cycle 3 or cycle 4, approximately 3 or 4 months
Secondary	Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at End of Induction Treatment	The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life.	Assessed at cycle 6, approximately 6 months
Secondary	Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Baseline	The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life.	Assessed at baseline
Secondary	Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Mid-induction Treatment	The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life.; FACIT-Fatigue subscale score at cycle 3 is considered as mid-treatment score. If FACIT-Fatigue subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.	Assessed at cycle 3 or cycle 4, approximately 3 or 4 months
Secondary	Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at End of Induction Treatment	The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life.	Assessed at cycle 6, approximately 6 months
Secondary	Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Baseline	The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life.	Assessed at baseline
Secondary	Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Mid-induction Treatment	The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life.	Assessed at cycle 3, approximately 3 months
Secondary	Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at the End of Induction Treatment	The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life.	Assessed at end of induction treatment (cycle 6), approximately 6 months