LymphomaPhase 2NCT01415752
Rituximab, Bendamustine Hydrochloride, and Bortezomib Followed by Rituximab and Lenalidomide in Treating Older Patients With Previously Untreated Mantle Cell Lymphoma
A Phase 2 study testing rituximab, Bendamustine and bortezomib in people with Lymphoma and Mantle Cell Lymphoma, run by Eastern Cooperative Oncology Group at 418 sites in 2 countries.
Trial summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Lymphoma, Mantle Cell Lymphoma
- What is being tested?
- rituximab, Bendamustine and bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 373 participants
- Where
- 418 sitesin 2 countries
- Study dates
- 9 Aug 2012to Sep 2031
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Step 1 (Induction) Inclusion Criteria:
- Mantle Cell Lymphoma International Prognostic Index (MIPI) score must be calculated and entered in OPEN
- Histologically confirmed untreated mantle cell lymphoma (MCL), with documented cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH)
- Patients must have at least one objective measurable disease parameter
- Negative pregnancy test
- Women of childbearing potential and sexually active males use an accepted and effective method of contraception
- ECOG performance status 0-2
- Absolute neutrophil count (ANC) ≥ 1,500/mcL (1.5 x 10^9/L)
- Platelets ≥ 100,000/mcL (100 x 10^9/L)
- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2 times upper limit of normal (ULN)
- Bilirubin ≤ 2 times ULN
- Calculated creatinine clearance by Cockroft-Gault formula ≥ 30 mL/min
- Patient agrees that if randomized to Arms C or D, and proceeding onto Arms G or H, they must register into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist. Patients must have no medical contra-indications to, and be willing to take, DVT prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have deep vein thrombosis (DVT) prophylaxis. Patients randomized to Arms G or H who have 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. Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis. Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment or another accepted full anticoagulation regimen. Ways to minimize risk of DVT should be discussed with patients, including, but not limited to, avoiding smoking, minimizing prothrombotic hormone replacement, avoiding prolonged periods of inactivity (e.g. uninterrupted long car or plane trips).
- HIV-positive patients are not excluded but, to enroll, must meet all of the below criteria:
- HIV is sensitive to antiretroviral therapy
- Must be willing to take effective antiretroviral therapy, if indicated
- CD4 count at screening >= 300 cells/mm³
- 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 until at least 2 months following the completion of therapy or until the CD4 cells recover to over 250 cells/mm³, whichever occurs later
Step 1 (Induction) Exclusion Criteria:
- Women (sexually mature female) must not be pregnant or breast-feeding
- Evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, low grade prostate carcinoma (Gleason grade ≤ 6) managed with observation that has been stable for at least 6 months, or any malignancy treated with curative intent continuously disease free for >=3 years so as not to interfere with interpretation of radiographic response
- Prior therapy for MCL, except: < 2 weeks of steroid therapy for symptom control or local radiation therapy for symptom control if there is measurable disease outside the radiation portal. Patients may be on chronic steroids for non-malignant disease if on a stable dose equivalent to ≤ 20 mg prednisone per day.
- CNS involvement
- History of AIDS-defining conditions
- Grade 2 or greater peripheral neuropathy.
- NYHA Class III or IV heart failure, uncontrolled angina severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
- Hypersensitivity to bortezomib, boron or mannitol
- A serious medical or psychiatric illness likely to interfere with study participation
- Participating in any other therapeutic clinical trial or taking any other experimental medications within 14 days prior to registration.
Step 2 (Maintenance) Inclusion Criteria:
- ECOG performance status between 0-2
- Complete response, partial response or stable disease after Step 1
- ANC >= 1000 cells/mm3 (1.0 x 10^9/L)
- Platelets >= 75,000 cells/mm3 (75 x 10^9/L)
- AST/ALT <= 2 x upper limit of normal (ULN)
- Total bilirubin <= 2 x upper limit of normal (ULN) or, if total elevated, direct bilirubin <= 2 x upper limit of normal (ULN)
- Calculated creatinine clearance by Cockroft-Gault formula >= 30 ml/min
- Patient agrees that if randomized to Arms C or D, and proceeding onto Arms G or H, they must register into the mandatory REMS program, and be willing and able to comply with the requirements of REMS.
- Pregnancy tests must occur within 10 - 14 days and again within 24 hours prior to initiation of Cycle 1 of lenalidomide.
- Females of childbearing potential (FCBP)* with regular or no menstruation must have a pregnancy test weekly for the first 28 days and then every 28 days while on lenalidomide therapy (including breaks in therapy); at discontinuation of lenalidomide and at Day 28 post the last dose of lenalidomide. Females with irregular menstruation must have a pregnancy test weekly for the first 28 days and then every 14 days while on lenalidomide therapy (including breaks in therapy), at discontinuation of lenalidomide and at Day 14 and Day 28 post the last dose of lenalidomide (see Appendix VI: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods).
- Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- A female of childbearing potential is any sexually mature female, regardless of sexual orientation of whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- 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/lenaliomide: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study including interruptions in therapy; 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.
- Women must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from protocol treatment.
- Males must agree to abstain from donating blood, semen, or sperm 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 all cycles of study treatment and for at least 28 days following discontinuation of protocol treatment
- Patients must have no medical contra-indications to, and be willing to take, DVT prophylaxis as all patients registering to the lenalidomide/rituximab Arms G and H will be required to have deep vein thrombosis (DVT) prophylaxis. Patients randomized to Arms G or H who have full anticoagulation, a history of a thrombotic vascular event will be required to have 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. Patients on Arms G and H without a history of a thromboembolic event are required to take a daily aspirin (81 mg or 325 mg) for DVT prophylaxis. Patients who are unable to tolerate aspirin should receive low molecular weight heparin therapy or warfarin treatment or another accepted full anticoagulation regimen. Ways to minimize risk of DVT should be discussed with patients, including, but not limited to, avoiding smoking, minimizing pro-thrombotic hormone replacement, avoiding prolonged periods of inactivity (e.g. uninterrupted long car or plane trips).
Trial locations and contacts
418 sites in 2 countries.
302 sites in 2 countries
United States300 sites
Oncare Hawaii Inc-Pali Momi
‘Aiea, Hawaii, 96701
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
Summa Akron City Hospital/Cooper Cancer Center
Akron, Ohio, 44304
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic PC-William R Bliss Cancer Center
Ames, Iowa, 50010
Alaska Breast Care and Surgery LLC
Anchorage, Alaska, 99508
Alaska Women's Cancer Care
Anchorage, Alaska, 99508
Anchorage Oncology Centre
Anchorage, Alaska, 99508
Katmai Oncology Group
Anchorage, Alaska, 99508
Providence Alaska Medical Center
Anchorage, Alaska, 99508
AnMed Health Cancer Center
Anderson, South Carolina, 29621
Saint Joseph Mercy Hospital
Ann Arbor, Michigan, 48106-0995
Michigan Cancer Research Consortium Community Clinical Oncology Program
Ann Arbor, Michigan, 48106
Langlade Hospital and Cancer Center
Antigo, Wisconsin, 54409
Kaiser Permanente-Deer Valley Medical Center
Antioch, California, 94531
Hematology Oncology Associates of Central New York-Auburn
Auburn, New York, 13021
Harold Alfond Center for Cancer Care
Augusta, Maine, 04330
Rocky Mountain Cancer Centers-Aurora
Aurora, Colorado, 80012
The Medical Center of Aurora
Aurora, Colorado, 80012
Franklin Square Hospital Center
Baltimore, Maryland, 21237
Eastern Maine Medical Center
Bangor, Maine, 04401
Summa Barberton Hospital
Barberton, Ohio, 44203
Ochsner Health Center-Summa
Baton Rouge, Louisiana, 70809
Bronson Battle Creek
Battle Creek, Michigan, 49017
Cleveland Clinic Cancer Center Beachwood
Beachwood, Ohio, 44122
Sanford Clinic North-Bemidgi
Bemidji, Minnesota, 56601
Hematology Oncology Associates-Quad Cities
Bettendorf, Iowa, 52722
Spectrum Health Big Rapids Hospital
Big Rapids, Michigan, 49307
Montana Cancer Consortium CCOP
Billings, Montana, 59101
Saint Vincent Healthcare
Billings, Montana, 59101
Frontier Cancer Center and Blood Institute-Billings
Billings, Montana, 59102
Billings Clinic Cancer Center
Billings, Montana, 59107
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Parkland Health Center-Bonne Terre
Bonne Terre, Missouri, 63628
McFarland Clinic PC-Boone
Boone, Iowa, 50036
Tufts Medical Center
Boston, Massachusetts, 02111
Boulder Community Hospital
Boulder, Colorado, 80301
Rocky Mountain Cancer Centers-Boulder
Boulder, Colorado, 80304
Bozeman Deaconess Hospital
Bozeman, Montana, 59715
Wellmont Bristol Regional Medical Center
Bristol, Tennessee, 37620
Wellmont Medical Associates Oncology and Hematology-Bristol
Bristol, Tennessee, 37620
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, 59701
Cooper Hospital University Medical Center
Camden, New Jersey, 08103
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Southeast Cancer Center
Cape Girardeau, Missouri, 63703
Memorial Hospital of Carbondale
Carbondale, Illinois, 62902
Rocky Mountain Oncology
Casper, Wyoming, 82609
Cedar Rapids Oncology Association
Cedar Rapids, Iowa, 52403
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Centralia Oncology Clinic
Centralia, Illinois, 62801
University of Virginia
Charlottesville, Virginia, 22908
Mount Sinai Hospital Medical Center
Chicago, Illinois, 60608
Hematology and Oncology Associates
Chicago, Illinois, 60611
Northwestern University
Chicago, Illinois, 60611
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612-3785
Oncology Hematology Care Inc-Mercy West
Cincinnati, Ohio, 45211
Oncology and Hematology Care Inc-Taft
Cincinnati, Ohio, 45219
Oncology Hematology Care Inc - Anderson
Cincinnati, Ohio, 45230
Oncology Hematology Care Inc - Kenwood
Cincinnati, Ohio, 45236
Oncology Hematology Care Inc-Blue Ash
Cincinnati, Ohio, 45242
University of Cincinnati
Cincinnati, Ohio, 45267
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Case Western Reserve University
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio, 44111
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328
Big Horn Basin Cancer Center
Cody, Wyoming, 82414
Billings Clinic-Cody
Cody, Wyoming, 82414
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, 80907
Rocky Mountain Cancer Centers-Penrose
Colorado Springs, Colorado, 80907
University of Missouri - Ellis Fischel
Columbia, Missouri, 65212
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210
Mercy Hospital
Coon Rapids, Minnesota, 55433
Oncology Hematology Care Inc-Crestview
Crestview Hills, Kentucky, 41017
Parkland Memorial Hospital
Dallas, Texas, 75235
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Carle on Vermilion
Danville, Illinois, 61832
Geisinger Medical Center
Danville, Pennsylvania, 17822
Grandview Hospital
Dayton, Ohio, 45405
Good Samaritan Hospital - Dayton
Dayton, Ohio, 45406
Miami Valley Hospital
Dayton, Ohio, 45409
Samaritan North Health Center
Dayton, Ohio, 45415
Dayton CCOP
Dayton, Ohio, 45420
Oakwood Hospital and Medical Center
Dearborn, Michigan, 48124
Cancer Care Center of Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Kaiser Permanente-Franklin
Denver, Colorado, 80205
Porter Adventist Hospital
Denver, Colorado, 80210
Exempla Saint Joseph Hospital
Denver, Colorado, 80218
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, 80218
Rocky Mountain Cancer Centers-Midtown
Denver, Colorado, 80218
Rocky Mountain Cancer Centers-Rose
Denver, Colorado, 80220
Rose Medical Center
Denver, Colorado, 80220
Colorado Cancer Research Program CCOP
Denver, Colorado, 80224-2522
Colorado Blood Cancer Institute
Denver, Colorado, 80907
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Saint John Hospital and Medical Center
Detroit, Michigan, 48236
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Essentia Health Saint Mary's Medical Center
Duluth, Minnesota, 55805
Miller-Dwan Hospital
Duluth, Minnesota, 55805
Mercy Medical Center
Durango, Colorado, 81301
Southwest Oncology PC
Durango, Colorado, 81301
Veterans Adminstration New Jersey Health Care System
East Orange, New Jersey, 07018-1095
Hematology Oncology Associates of Central New York-East Syracuse
East Syracuse, New York, 13057
Marshfield Clinic Cancer Center at Sacred Heart
Eau Claire, Wisconsin, 54701
Sacred Heart Hospital
Eau Claire, Wisconsin, 54701
Fairview-Southdale Hospital
Edina, Minnesota, 55435
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Union Hospital of Cecil County
Elkton, Maryland, 21921
Mercy Cancer Center-Elyria
Elyria, Ohio, 44035
Comprehensive Cancer Care and Research Institute of Colorado LLC
Englewood, Colorado, 80113
Swedish Medical Center
Englewood, Colorado, 80113
Green Bay Oncology - Escanaba
Escanaba, Michigan, 49431
Oncology Hematology Care Inc-Healthplex
Fairfield, Ohio, 45014
Roger Maris Cancer Center
Fargo, North Dakota, 58122
Sanford Clinic North-Fargo
Fargo, North Dakota, 58122
Sanford Medical Center-Fargo
Fargo, North Dakota, 58122
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Blanchard Valley Hospital
Findlay, Ohio, 45840
Simonds-Sinon Regional Cancer Center
Fitchburg, Massachusetts, 01420
Hurley Medical Center
Flint, Michigan, 48502
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Agnesian Cancer Center
Fond du Lac, Wisconsin, 54935
Poudre Valley Hospital
Fort Collins, Colorado, 80524
McFarland Clinic PC-Trinity Cancer Center
Fort Dodge, Iowa, 50501
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Kaiser Permanente, Fremont
Fremont, California, 94538
Kaiser Permanente
Fresno, California, 93720
Unity Hospital
Fridley, Minnesota, 55432
Glens Falls Hospital
Glens Falls, New York, 12801
Mountain Blue Cancer Care Center
Golden, Colorado, 80401
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534
Wayne Memorial Hospital
Goldsboro, North Carolina, 27534
Genesys Regional Medical Center
Grand Blanc, Michigan, 48439
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, 49503
Mercy Health Saint Mary's
Grand Rapids, Michigan, 49503
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, 49503
Benefis Healthcare- Sletten Cancer Institute
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
North Colorado Medical Center
Greeley, Colorado, 80631
Green Bay Oncology at Saint Vincent Hospital
Green Bay, Wisconsin, 54301-3526
Saint Vincent Hospital
Green Bay, Wisconsin, 54301
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, 54303
Saint Mary's Hospital
Green Bay, Wisconsin, 54303
Wayne Hospital
Greenville, Ohio, 45331
Saint Francis Hospital
Greenville, South Carolina, 29601
Rocky Mountain Cancer Centers-Greenwood Village
Greenwood Village, Colorado, 80111
Gibbs Cancer Center-Pelham
Greer, South Carolina, 29651
Saint Francis Hospital and Medical Center
Hartford, Connecticut, 06105
Northern Montana Hospital
Havre, Montana, 59501
Geisinger Medical Center-Cancer Center Hazleton
Hazleton, Pennsylvania, 18201
Saint Peter's Community Hospital
Helena, Montana, 59601
Hendersonville Hematology and Oncology at Pardee
Hendersonville, North Carolina, 28739
Margaret R Pardee Memorial Hospital
Hendersonville, North Carolina, 28791
Park Ridge Hospital Breast Health Center
Hendersonville, North Carolina, 28792
Hematology Oncology Associates of Illinois-Highland Park
Highland Park, Illinois, 60035
Oncare Hawaii Inc-POB II
Honolulu, Hawaii, 96813
Queen's Medical Center
Honolulu, Hawaii, 96813
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
OnCare Hawaii-Liliha
Honolulu, Hawaii, 96817-3169
Oncare Hawaii Inc-Kuakini
Honolulu, Hawaii, 96817
Kaiser Permanente Moanalua Medical Center
Honolulu, Hawaii, 96819
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350
Centerpoint Medical Center LLC
Independence, Missouri, 64057
Cleveland Clinic Cancer Center Independence
Independence, Ohio, 44131
Green Bay Oncology - Iron Mountain
Iron Mountain, Michigan, 49801
Allegiance Health
Jackson, Michigan, 49201
Baptist Cancer Institute
Jacksonville, Florida, 32207
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546
McFarland Clinic PC-Jefferson
Jefferson, Iowa, 50129
Capital Region Medical Center-Goldschmidt Cancer Center
Jefferson City, Missouri, 65109
UW Cancer Center Johnson Creek
Johnson Creek, Wisconsin, 53038
Freeman Health System
Joplin, Missouri, 64804
Castle Medical Center
Kailua, Hawaii, 96734
Borgess Medical Center
Kalamazoo, Michigan, 49001
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Glacier Oncology PLLC
Kalispell, Montana, 59901
Kalispell Medical Oncology
Kalispell, Montana, 59901
Kalispell Regional Medical Center
Kalispell, Montana, 59901
Presence Saint Mary's Hospital
Kankakee, Illinois, 60901
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
Heartland Hematology and Oncology Associates Incorporated
Kansas City, Missouri, 64118
Research Medical Center
Kansas City, Missouri, 64132
Kadlec Clinic Hematology and Oncology
Kennewick, Washington, 99336
Kettering Medical Center
Kettering, Ohio, 45429
Wellmont Holston Valley Hospital and Medical Center
Kingsport, Tennessee, 37660
Wellmont Medical Associates Oncology and Hematology-Kingsport
Kingsport, Tennessee, 37660
Kinston Medical Specialists PA
Kinston, North Carolina, 28501
EvergreenHealth Medical Center
Kirkland, Washington, 98033
Seattle Cancer Care Alliance at EvergreenHealth
Kirkland, Washington, 98034
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Kaiser Permanente-Rock Creek
Lafayette, Colorado, 80026
IU Health Arnett Cancer Care
Lafayette, Indiana, 47904
Rocky Mountain Cancer Centers-Lakewood
Lakewood, Colorado, 80228
Saint Anthony Hospital
Lakewood, Colorado, 80228
Sparrow Hospital
Lansing, Michigan, 48912
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Saint Luke's East - Lee's Summit
Lee's Summit, Missouri, 64086
Beebe Medical Center
Lewes, Delaware, 19958
Geisinger Medical Oncology at Evangelical Community Hospital
Lewisburg, Pennsylvania, 17837
Lewistown Hospital
Lewistown, Pennsylvania, 17044
Liberty Radiation Oncology Center
Liberty, Missouri, 64068
North Shore Hematology Oncology
Libertyville, Illinois, 60048
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue, Hawaii, 96766
Rocky Mountain Cancer Centers-Littleton
Littleton, Colorado, 80120
Littleton Adventist Hospital
Littleton, Colorado, 80122
Hematology Oncology Associates of Central New York-Liverpool
Liverpool, New York, 13088
Saint Mary Mercy Hospital
Livonia, Michigan, 48154
Kaiser Permanente-Lone Tree
Lone Tree, Colorado, 80124
Rocky Mountain Cancer Centers-Sky Ridge
Lone Tree, Colorado, 80124
Sky Ridge Medical Center
Lone Tree, Colorado, 80124
Longmont United Hospital
Longmont, Colorado, 80501
Rocky Mountain Cancer Centers-Longmont
Longmont, Colorado, 80501
Saint John Medical Center
Longview, Washington, 98632
Los Angeles County-USC Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
McKee Medical Center
Loveland, Colorado, 80539
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Holy Family Memorial Hospital
Manitowoc, Wisconsin, 54221
Cleveland Clinic Cancer Center Mansfield
Mansfield, Ohio, 44906
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Bay Area Medical Center
Marinette, Wisconsin, 54143
McFarland Clinic PC-Marshalltown
Marshalltown, Iowa, 50158
Marshfield Clinic
Marshfield, Wisconsin, 54449
Saint Joseph's Hospital
Marshfield, Wisconsin, 54449
Memorial Hospital Of Martinsville
Martinsville, Virginia, 24115
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio, 44124
Lake University Ireland Cancer Center
Mentor, Ohio, 44060
Idaho Urologic Institute-Meridian
Meridian, Idaho, 83642
Franciscan Saint Anthony Health-Michigan City
Michigan City, Indiana, 46360
Woodland Cancer Care Center
Michigan City, Indiana, 46360
Orange Regional Medical Center
Middletown, New York, 10940
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Providence Milwaukie Hospital
Milwaukie, Oregon, 97222
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Health Partners Inc
Minneapolis, Minnesota, 55454
Marshfield Clinic-Minocqua Center
Minocqua, Wisconsin, 54548
Community Medical Hospital
Missoula, Montana, 59801
Montana Cancer Specialists
Missoula, Montana, 59802
Saint Patrick Hospital - Community Hospital
Missoula, Montana, 59802
Kaiser Permanente-Modesto
Modesto, California, 95356
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Good Samaritan Regional Health Center
Mount Vernon, Illinois, 62864
Skagit Valley Hospital Regional Cancer Care Center
Mount Vernon, Washington, 98273
Skagit Valley Hospital
Mount Vernon, Washington, 98274
D N Greenwald Center
Mukwonago, Wisconsin, 53149
Mercy Health Mercy Campus
Muskegon, Michigan, 49444
Norris Cotton Cancer Center Nashua
Nashua, New Hampshire, 03063
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
Ochsner Baptist Medical Center
New Orleans, Louisiana, 70115
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017
New Ulm Medical Center
New Ulm, Minnesota, 56073
Mount Sinai Medical Center
New York, New York, 10029
Weill Medical College of Cornell University
New York, New York, 10065
Christiana Gynecologic Oncology LLC
Newark, Delaware, 19713
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware, 19713
Helen F Graham Cancer Center
Newark, Delaware, 19713
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Regional Hematology and Oncology PA
Newark, Delaware, 19713
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
Providence Newberg Medical Center
Newberg, Oregon, 97132
Illinois Cancer Specialists-Niles
Niles, Illinois, 60714
Lakeland Community Hospital
Niles, Michigan, 49120
Southwest VA Regional Cancer Center
Norton, Virginia, 24273
Kaiser Permanente-Oakland
Oakland, California, 94611
Oconomowoc Memorial Hospital-ProHealth Care Inc
Oconomowoc, Wisconsin, 53066-3896
Green Bay Oncology - Oconto Falls
Oconto Falls, Wisconsin, 54154
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045
UF Cancer Center at Orlando Health
Orlando, Florida, 32806
Menorah Medical Center
Overland Park, Kansas, 66209
Saint Luke's South Hospital
Overland Park, Kansas, 66213
Parker Adventist Hospital
Parker, Colorado, 80138
Rocky Mountain Cancer Centers-Parker
Parker, Colorado, 80138
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Saint Joseph Mercy Oakland
Pontiac, Michigan, 48341
Olympic Medical Center
Port Angeles, Washington, 98362
Saint Joseph Mercy Port Huron
Port Huron, Michigan, 48060
Providence Portland Medical Center
Portland, Oregon, 97213
Western Oncology Research Consortium
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Kootenai Cancer Center
Post Falls, Idaho, 83854
Pottstown Memorial Medical Center
Pottstown, Pennsylvania, 19464
Geisinger Medical Oncology-Pottsville
Pottsville, Pennsylvania, 17901
Kansas City CCOP
Prairie Village, Kansas, 66208
Saint Mary Corwin Medical Center
Pueblo, Colorado, 81004
Rocky Mountain Cancer Centers - Pueblo
Pueblo, Colorado, 81008
Kaiser Permanente-Redwood City
Redwood City, California, 94063
Canada2 sites
The Moncton Hospital
Moncton, New Brunswick, E1C 6Z8
Allan Blair Cancer Centre
Regina, Saskatchewan, S4T 7T1
About this study
Official title: Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.
PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- To determine whether the addition of bortezomib (RBV) to an induction regimen of rituximab-bendamustine (RB) improves progression-free survival (PFS) compared to RB alone in patients with previously untreated mantle cell lymphoma.
- To determine whether the addition of lenalidomide to a consolidation regimen of rituximab following an induction regimen of RB or RBV improves PFS compared to consolidation rituximab alone in this patient population.
Secondary
- To determine whether the addition of bortezomib to induction therapy improves the positron emission tomography (PET)-documented complete response (CR) rate compared to RB alone.
- To determine the objective response rate (ORR) for RB and RBV.
- Among patients who do not have PET-documented CR at the end of induction, to determine whether the addition of lenalidomide to consolidation therapy improves CR and ORR compared with rituximab alone.
- To determine overall survival (OS) in the treatment arms.
- To determine safety, with attention to the addition of bortezomib in the induction regimen and lenalidomide-rituximab (LR) as consolidation therapy.
Laboratory
- To collect paraffin-embedded tissue for creation of tissue microarray.
- To collect and bank serum and blood mononuclear cells for future studies.
- To collect formalin-fixed paraffin-embedded (FFPE) tissue to analyze potential prognostic factors (Ki-67 proliferation index by immunohistochemistry and correlation with proposed 5-gene set of proliferation markers analyzed by RNA PCR; SOX 11 expression by immunohistochemistry; and Micro-RNA levels by microarray).
Quality of Life
- Using patient-reported outcomes data, to determine the extent and severity of neuropathy associated with the addition of bortezomib to induction treatment.
- Using patient-reported outcomes data, to determine the extent and severity of fatigue associated with the addition of lenalidomide to consolidation treatment.
- To evaluate the effects of the addition of bortezomib and lenalidomide on patient-reported health-related quality of life.
- To evaluate the effects of bortezomib-related neuropathy on patient-reported health-related quality of life.
- To evaluate the response of lymphoma-specific symptoms to treatment.
- Using longitudinal patient-reported outcomes data, to describe the trajectory of lymphoma symptoms, neuropathy, fatigue, and overall health-related quality of life prior to, during, and following treatment among older adults with MCL.
Imaging
- To assess the proportion of patients up and down staging when fludeoxyglucose F 18- (FDG) PET/CT is added to standard Ann Arbor staging.
- To assess the ability of pre-treatment FDG-PET/CT (SUVmax) to predict response rate and PFS.
- Among patients with interim (post-cycle 3) FDG-PET/CT imaging, to assess the correlation of interim FDG-PET/CT imaging with response rate and PFS both during induction and consolidation therapy.
- To assess standard FDG-PET/CT metrics including SUVmax, tumor metabolic burden, total tumor burden, and association with pathology features (blastoid variant vs other, and Ki67) in the setting of MCL.
- To assess differences in overall and CR rates when using Deauville vs International Harmonization Project FDG-PET/CT interpretation criteria.
- To determine whether there is a correlation between FDG-PET/CT response and residual disease assessment by molecular and/or flow cytometric techniques.
Residual Disease Assessment by Molecular and Flow Cytometric Techniques
- To determine whether the number of malignant cells in circulation predict the number of cells in marrow.
- To determine whether the number of malignant cells in circulation/in marrow at the end of induction correlate with CR and 2-year PFS.
- To determine whether there is a higher rate of minimal residual disease (MRD) negativity among patients randomized to RBV as compared with RB, and among patients treated with LR maintenance compared with rituximab.
- To compare the two methods of MRD detection - molecular techniques and flow cytometry - as prognostic markers for outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to mantle cell lymphoma International Prognostic Index risk score (low vs intermediate vs high). Patients are randomized to 1 of 4 treatment arms.
- Arm A: Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm E: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
- Arm B: Patients receive induction therapy comprising bortezomib IV or subcutaneously (SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm F: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
- Arm C: Patients receive induction therapy comprising rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm G: Patients receive consolidation therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
- Arm D: Patients receive bortezomib, rituximab, and bendamustine hydrochloride as patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm H: Patients receive consolidation therapy comprising lenalidomide PO daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood and bone marrow sample collection at baseline and during treatment for correlative studies.
Patients complete the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym), the FACT/GOG-Neurotoxicity scale (FACT/GOG-Ntx), FACT-Fatigue, and FACT-General questionnaires at baseline and periodically during study and follow up.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 10 years.
- Conditions
- Lymphoma, Mantle Cell Lymphoma
- Being tested
- rituximab, Bendamustine, bortezomib, lenalidomide
- Keywords
- Lymphoma, Mantle Cell Lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
Also called IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan
Given IV
BendamustineDrug
Also called bendamustine hydrochloride, CEP-18083, TREANDA, BENDEKA
Given IV
bortezomibDrug
Also called MLN341, LDP-341, Velcade®
Given IV or SC
lenalidomideDrug
Also called IMiDTM compound CC-5013, Revlimid®
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab | Experimental | Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment.
Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Drug: Bendamustine |
| Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab | Experimental | Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment.
Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Drug: Bendamustine; Drug: bortezomib |
| Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab | Experimental | Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients then proceed to maintenance treatment.
Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Drug: Bendamustine; Drug: lenalidomide |
| Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab | Experimental | Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment.
Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Drug: Bendamustine; Drug: bortezomib; Drug: lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) for Induction Phase
PFS is defined as time from randomization to lymphoma progression or death. Progression is defined as:
- Appearance of any new lesion >1.5 cm in any axis during or at the end of therapy
- >=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions.
- >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.
- Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systems
Measured: Assessed at baseline, every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months
Progression-free Survival (PFS) for Maintenance Phase (Step 2)
PFS is defined as time from Step 2 registration to lymphoma progression or death. Progression is defined as:
- Appearance of any new lesion >1.5 cm in any axis during or at the end of therapy
- >=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions.
- >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.
- Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systems
Measured: Assessed at registration to step 2, cycles 6, 12, 18, treatment completion, then every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months
Secondary outcomes (4)
Objective Response for Induction Phase (Step 1)
Objective response is defined as either complete response (CR) or partial response (PR).
CR is defined as disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.
PR is defined as:
- ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses
- No increase in the size of other nodes, liver or spleen.
- Bone marrow assessment is irrelevant for determination of a PR if the sample was positive prior to treatment. However, if positive, the cell type should be specified, e.g. large-cell lymphoma or small cleaved cell lymphoma.
- No new sites of disease.
- Patients who achieve a CR but have persistent morphologic bone marrow involvement will be considered partial responders.
- When the bone marrow was involved before therapy and a clinical CR was achieved, but with no bone marrow assessment after treatment, patients are considered partial responders.
Measured: Assessed at baseline and 24 weeks (end of cycle 6)
PET-documented Complete Response for Induction Phase (Step 1)
Complete response is defined as disappearance of all detectable clinical evidence of disease.
Measured: Assessed at baseline and 24 weeks (end of cycle 6)
Overall Survival (OS) Rate at 5 Years Since Maintenance (Step 2)
OS is defined as the time from registration of Step 2 (maintenance) until death from any cause or last know alive. The Kaplan-Meier estimate of 5-year OS rate is reported.
Measured: Assessed every 3 months for 2.5 years, every 6 months for years 2.5-5
Objective Response for Maintenance (Step 2) Among Patients Without PET-documented CR at the End of Induction
Objective response is defined as either complete response (CR) or partial response (PR).
CR is defined as disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.
PR is defined as:
- ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses
- No increase in the size of other nodes, liver or spleen.
- Bone marrow assessment is irrelevant for determination of a PR if the sample was positive prior to treatment. However, if positive, the cell type should be specified, e.g. large-cell lymphoma or small cleaved cell lymphoma.
- No new sites of disease.
- Patients who achieve a CR but have persistent morphologic bone marrow involvement will be considered partial responders.
- When the bone marrow was involved before therapy and a clinical CR was achieved, but with no bone marrow assessment after treatment, patients are considered partial responders.
Measured: Assessed at baseline and every 4 months for 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2011 (estimated)
- Study start9 Aug 2012
- Primary completion25 Feb 2023
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 373 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eastern Cooperative Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mitchell R. Smith, MD, PhD, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01415752
- Sponsor's protocol ID
- E1411
- Other IDs
- NCI-2011-02980, CDR0000707057
- Status last verified
- May 2026
- First submitted
- 11 Aug 2011
- Last updated
- 3 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Publications
Smith MR, Jegede OA, Martin P, Till BG, Parekh SS, Yang DT, Hsi ED, Witzig T, Dave S, Scott D, Hanson C, Kostakoglu Shields L, Abdel-Samad N, Casulo C, Bartlett NL, Caimi PF, Al Baghdadi T, Blum KA, Romer MD, Inwards DJ, Lerner RE, Wagner LI, Little RF, Friedberg JW, Leonard JP, Kahl BS. Randomized study of induction with bendamustine-rituximab +/- bortezomib and maintenance with rituximab +/- lenalidomide for MCL. Blood. 2024 Sep 5;144(10):1083-1092. doi: 10.1182/blood.2024023962.
PubMed 38820500
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intergroup Randomized Phase 2 Four Arm Study In Patients ≥ 60 With Previously Untreated Mantle Cell Lymphoma Of Therapy With: Arm A = Rituximab+ Bendamustine Followed By Rituximab Consolidation (RB → R); Arm B = Rituximab + Bendamustine + Bortezomib Followed By Rituximab Consolidation (RBV→ R), Arm C = Rituximab + Bendamustine Followed By Lenalidomide + Rituximab Consolidation (RB → LR) or Arm D = Rituximab + Bendamustine + Bortezomib Followed By Lenalidomide + Rituximab Consolidation (RBV → LR)
- ClinicalTrials.gov ID
- NCT01415752
- Acronym / sponsor ID
- E1411
- Conditions
- Lymphoma, Mantle Cell Lymphoma
- Keywords
- Lymphoma, Mantle Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 373 participants (actual)
- Lead sponsor
- Eastern Cooperative Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 9 Aug 2012 (actual)
- Primary completion
- 25 Feb 2023 (actual)
- Study completion
- Sep 2031 (estimated)
- First posted
- 12 Aug 2011 (estimated)
- Results
- Posted 8 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma.
PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.
Detailed description
OBJECTIVES:
Primary
- To determine whether the addition of bortezomib (RBV) to an induction regimen of rituximab-bendamustine (RB) improves progression-free survival (PFS) compared to RB alone in patients with previously untreated mantle cell lymphoma.
- To determine whether the addition of lenalidomide to a consolidation regimen of rituximab following an induction regimen of RB or RBV improves PFS compared to consolidation rituximab alone in this patient population.
Secondary
- To determine whether the addition of bortezomib to induction therapy improves the positron emission tomography (PET)-documented complete response (CR) rate compared to RB alone.
- To determine the objective response rate (ORR) for RB and RBV.
- Among patients who do not have PET-documented CR at the end of induction, to determine whether the addition of lenalidomide to consolidation therapy improves CR and ORR compared with rituximab alone.
- To determine overall survival (OS) in the treatment arms.
- To determine safety, with attention to the addition of bortezomib in the induction regimen and lenalidomide-rituximab (LR) as consolidation therapy.
Laboratory
- To collect paraffin-embedded tissue for creation of tissue microarray.
- To collect and bank serum and blood mononuclear cells for future studies.
- To collect formalin-fixed paraffin-embedded (FFPE) tissue to analyze potential prognostic factors (Ki-67 proliferation index by immunohistochemistry and correlation with proposed 5-gene set of proliferation markers analyzed by RNA PCR; SOX 11 expression by immunohistochemistry; and Micro-RNA levels by microarray).
Quality of Life
- Using patient-reported outcomes data, to determine the extent and severity of neuropathy associated with the addition of bortezomib to induction treatment.
- Using patient-reported outcomes data, to determine the extent and severity of fatigue associated with the addition of lenalidomide to consolidation treatment.
- To evaluate the effects of the addition of bortezomib and lenalidomide on patient-reported health-related quality of life.
- To evaluate the effects of bortezomib-related neuropathy on patient-reported health-related quality of life.
- To evaluate the response of lymphoma-specific symptoms to treatment.
- Using longitudinal patient-reported outcomes data, to describe the trajectory of lymphoma symptoms, neuropathy, fatigue, and overall health-related quality of life prior to, during, and following treatment among older adults with MCL.
Imaging
- To assess the proportion of patients up and down staging when fludeoxyglucose F 18- (FDG) PET/CT is added to standard Ann Arbor staging.
- To assess the ability of pre-treatment FDG-PET/CT (SUVmax) to predict response rate and PFS.
- Among patients with interim (post-cycle 3) FDG-PET/CT imaging, to assess the correlation of interim FDG-PET/CT imaging with response rate and PFS both during induction and consolidation therapy.
- To assess standard FDG-PET/CT metrics including SUVmax, tumor metabolic burden, total tumor burden, and association with pathology features (blastoid variant vs other, and Ki67) in the setting of MCL.
- To assess differences in overall and CR rates when using Deauville vs International Harmonization Project FDG-PET/CT interpretation criteria.
- To determine whether there is a correlation between FDG-PET/CT response and residual disease assessment by molecular and/or flow cytometric techniques.
Residual Disease Assessment by Molecular and Flow Cytometric Techniques
- To determine whether the number of malignant cells in circulation predict the number of cells in marrow.
- To determine whether the number of malignant cells in circulation/in marrow at the end of induction correlate with CR and 2-year PFS.
- To determine whether there is a higher rate of minimal residual disease (MRD) negativity among patients randomized to RBV as compared with RB, and among patients treated with LR maintenance compared with rituximab.
- To compare the two methods of MRD detection - molecular techniques and flow cytometry - as prognostic markers for outcome.
OUTLINE: This is a multicenter study. Patients are stratified according to mantle cell lymphoma International Prognostic Index risk score (low vs intermediate vs high). Patients are randomized to 1 of 4 treatment arms.
- Arm A: Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm E: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
- Arm B: Patients receive induction therapy comprising bortezomib IV or subcutaneously (SC) on days 1, 4, 8, and 11 and rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm F: Patients receive consolidation therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
- Arm C: Patients receive induction therapy comprising rituximab and bendamustine hydrochloride as patients in arm A. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm G: Patients receive consolidation therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
- Arm D: Patients receive bortezomib, rituximab, and bendamustine hydrochloride as patients in arm B. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm H: Patients receive consolidation therapy comprising lenalidomide PO daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Patients may undergo blood and bone marrow sample collection at baseline and during treatment for correlative studies.
Patients complete the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym), the FACT/GOG-Neurotoxicity scale (FACT/GOG-Ntx), FACT-Fatigue, and FACT-General questionnaires at baseline and periodically during study and follow up.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually for 10 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab | Experimental | Biological: rituximab, Drug: BendamustinePatients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. |
| Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab | Experimental | Biological: rituximab, Drug: Bendamustine, Drug: bortezomibPatients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. |
| Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab | Experimental | Biological: rituximab, Drug: Bendamustine, Drug: lenalidomidePatients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. |
| Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab | Experimental | Biological: rituximab, Drug: Bendamustine, Drug: bortezomib, Drug: lenalidomidePatients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximabAlso: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, RituxanGiven IV | Biological | Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab, Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab, Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab, Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab |
| BendamustineAlso: bendamustine hydrochloride, CEP-18083, TREANDA, BENDEKAGiven IV | Drug | Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab, Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab, Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab, Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab |
| bortezomibAlso: MLN341, LDP-341, Velcade®Given IV or SC | Drug | Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab, Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab |
| lenalidomideAlso: IMiDTM compound CC-5013, Revlimid®Given PO | Drug | Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab, Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab |
Primary outcome
Progression-free Survival (PFS) for Induction Phase
Time frame: Assessed at baseline, every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months
PFS is defined as time from randomization to lymphoma progression or death. Progression is defined as: * Appearance of any new lesion >1.5 cm in any axis during or at the end of therapy * >=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions. * >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis. * Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systems
Progression-free Survival (PFS) for Maintenance Phase (Step 2)
Time frame: Assessed at registration to step 2, cycles 6, 12, 18, treatment completion, then every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months
PFS is defined as time from Step 2 registration to lymphoma progression or death. Progression is defined as: * Appearance of any new lesion >1.5 cm in any axis during or at the end of therapy * >=50% increase from nadir in the sum of products of the diameters (SPD) of any previously involved nodes or extranodal masses, or in a single involved node or extranodal mass, or the size of other lesions. * >=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis. * Lesions should be PET positive if observed in a typical FDG-avid lymphoma or the lesion was PET positive before therapy unless the lesion is too small to be detected with current PET systems
4 secondary outcomes
Objective Response for Induction Phase (Step 1)
Time frame: Assessed at baseline and 24 weeks (end of cycle 6)
PET-documented Complete Response for Induction Phase (Step 1)
Time frame: Assessed at baseline and 24 weeks (end of cycle 6)
Overall Survival (OS) Rate at 5 Years Since Maintenance (Step 2)
Time frame: Assessed every 3 months for 2.5 years, every 6 months for years 2.5-5
Objective Response for Maintenance (Step 2) Among Patients Without PET-documented CR at the End of Induction
Time frame: Assessed at baseline and every 4 months for 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 38820500Smith MR, Jegede OA, Martin P, Till BG, Parekh SS, Yang DT, Hsi ED, Witzig T, Dave S, Scott D, Hanson C, Kostakoglu Shields L, Abdel-Samad N, Casulo C, Bartlett NL, Caimi PF, Al Baghdadi T, Blum KA, Romer MD, Inwards DJ, Lerner RE, Wagner LI, Little RF, Friedberg JW, Leonard JP, Kahl BS. Randomized study of induction with bendamustine-rituximab +/- bortezomib and maintenance with rituximab +/- lenalidomide for MCL. Blood. 2024 Sep 5;144(10):1083-1092. doi: 10.1182/blood.2024023962.
- Individual participant dataSharing planned: Yes. Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitchell R. Smith, MD, PhD principal investigator
Fox Chase Cancer Center
418 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rituximab, Bendamustine and bortezomib in people with Lymphoma and Mantle Cell Lymphoma, run by Eastern Cooperative Oncology Group at 418 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 418 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) for Induction Phase (time frame: Assessed at baseline, every 3 months for 2.5 years, every 6 months up to 10 years from end of treatment, and then annually up to 10 years and 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01415752, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.