Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

NCT ID: NCT00553644

Last Updated: 2018-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-15
• Study Completion Date: 2014-01-21

Brief Summary

This phase II trial studies how well bortezomib and lenalidomide work in treating patients with mantle cell lymphoma that has come back after a period of improvement (refractory) or is not responding to treatment (refractory). Bortezomib may also stop the growth of cancer cells by blocking some proteins needed for cell growth. Lenalidomide may stimulate the immune system to kill cancer cells and may also block the growth of new blood vessels necessary for cell growth. Giving bortezomib with lenalidomide may be an effective treatment for relapsed or refractory mantle cell lymphoma.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the overall response (complete response [CR] and partial response [PR]) rate and the complete response (CR) rate to bortezomib + lenalidomide therapy in patients with relapsed or refractory mantle cell lymphoma.

SECONDARY OBJECTIVES:

I. To determine the time to progression after therapy with bortezomib + lenalidomide in patients with relapsed or refractory mantle cell lymphoma.

II. To determine the disease-free survival and overall survival after therapy with bortezomib + lenalidomide in patients with relapsed or refractory mantle cell lymphoma.

OUTLINE:

Patients receive induction therapy comprising bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11 and lenalidomide orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response as best response after completion of induction therapy receive maintenance therapy comprising bortezomib IV on days 1 and 8 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 6 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually for 2 years.

Conditions

Recurrent Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (bortezomib, lenalidomide)

Patients receive induction therapy comprising bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response as best response after completion of induction therapy receive maintenance therapy comprising bortezomib IV on days 1 and 8 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 6 years in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Lenalidomide

Intervention Type: DRUG

Given PO

Interventions

Bortezomib

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Lenalidomide

Given PO

Intervention Type: DRUG

Other Intervention Names

[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid; LDP 341; MLN341; PS-341; PS341; Velcade; CC-5013; CC5013; CDC 501; Revlimid

Eligibility Criteria

Inclusion Criteria

• Histologically documented mantle cell lymphoma, with the following immunophenotypic characteristics: cluster of differentiation (CD)5+, CD23-, cyclin D1+; this may be from an initial diagnostic biopsy, or one obtained at time of relapse

• Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable
• Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation
• Institutional flow cytometry or immunohistochemistry must confirm CD5 antigen expression, lack of CD23 antigen expression, and expression of cyclin D1
• Prior therapy with at least one regimen, which may have been single agent or multi-agent, and consisted of traditional cytotoxic agents and/or biologic agents; patient may not have received prior bortezomib or lenalidomide therapy; patient must have progressive disease or refractory disease following that initial regimen(s); refractory disease will be defined as stable disease (SD) or progressive disease (PD) as best response to prior therapy, or CR or PR as initial response followed by disease progression within 6 months
• Prior autologous, but not allogeneic, stem cell transplant is allowed
• No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent
• No prior radioimmunotherapy within 12 months of study entry
• No >= grade 3 peripheral neuropathy within a month prior to study entry
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm by physical exam, computed tomography (CT), magnetic resonance imaging (MRI), or conventional radiograph is acceptable; lesions that are considered non-measurable include the following:

• Bone lesions (lesions, if present, should be noted)
• Ascites
• Pleural/pericardial effusion
• Lymphangitis cutis or pulmonis
• Bone marrow (involvement by non-Hodgkin lymphoma should be noted)
• No known central nervous system (CNS) involvement by lymphoma
• Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following: CD4+ cell count > 350/mm^3; treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3; no history of acquired immunodeficiency syndrome (AIDS)-defining conditions or other HIV-related illnesses; no concurrent zidovudine or stavudine
• Non-pregnant and non-nursing; 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 prior to registration; further, they 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 starting 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; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure; documentation of counseling is required on Cancer and Leukemia Group B (CALGB) form S-041
• Patients with a recent history (within 3 months of study entry) of deep vein thrombosis (DVT)/pulmonary embolism (PE) are not eligible; patients with a distant history (greater than 3 months before study entry) of DVT/PE are eligible, but must receive either prophylactic aspirin or low molecular weight heparin, unless contraindicated
• Left ventricular ejection fraction (LVEF) >= 45% by multigated acquisition (MUGA) scan or echocardiogram
• No New York Heart Association class III or class IV congestive heart failure at study entry
• No myocardial infarction within the past 6 months of study entry
• No known positivity for hepatitis A, B, or C
• Absolute neutrophil count (ANC) >= 1,000/uL (>= 500/uL if marrow involvement)
• Platelets >= 75,000/uL
• Creatinine =< 1.5 x upper limit of normal (ULN) (unless attributable to non-Hodgkin's lymphoma) and estimated creatinine clearance >= 30 mL/min (patients on dialysis are not eligible)
• Total bilirubin =< 2 x ULN (unless attributable to non-Hodgkin's lymphoma and Gilbert's disease)
• Urine (U)-human chorionic gonadotropin (HCG) or serum HCG negative

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vicki Morrison

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

Kaiser Permanente-Anaheim

Anaheim, California, United States

Kaiser Permanente-Baldwin Park

Baldwin Park, California, United States

Kaiser Permanente-Bellflower

Bellflower, California, United States

Kaiser Permanente-Fontana

Fontana, California, United States

Kaiser Permanente - Harbor City

Harbor City, California, United States

Kaiser Permanente-Irvine

Irvine, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Kaiser Permanente-Cadillac

Los Angeles, California, United States

Kaiser Permanente - Panorama City

Panorama City, California, United States

Kaiser Permanente-Riverside

Riverside, California, United States

Kaiser Permanente-San Diego Mission

San Diego, California, United States

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Kaiser Permanente-San Marcos

San Marcos, California, United States

Kaiser Permanente-Woodland Hills

Woodland Hills, California, United States

Hartford Hospital

Hartford, Connecticut, United States

Beebe Medical Center

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Graham Hospital Association

Canton, Illinois, United States

Memorial Hospital

Carthage, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Heartland Cancer Research NCORP

Decatur, Illinois, United States

Eureka Hospital

Eureka, Illinois, United States

Galesburg Cottage Hospital

Galesburg, Illinois, United States

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Western Illinois Cancer Treatment Center

Galesburg, Illinois, United States

Mason District Hospital

Havana, Illinois, United States

Hopedale Medical Complex - Hospital

Hopedale, Illinois, United States

Mcdonough District Hospital

Macomb, Illinois, United States

Bromenn Regional Medical Center

Normal, Illinois, United States

Community Cancer Center Foundation

Normal, Illinois, United States

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Ottawa Regional Hospital and Healthcare Center

Ottawa, Illinois, United States

OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center

Pekin, Illinois, United States

Pekin Hospital

Pekin, Illinois, United States

Proctor Hospital

Peoria, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Illinois Valley Hospital

Peru, Illinois, United States

Valley Radiation Oncology

Peru, Illinois, United States

Perry Memorial Hospital

Princeton, Illinois, United States

Saint Margaret's Hospital

Spring Valley, Illinois, United States

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

University of Iowa Healthcare Cancer Services Quad Cities

Bettendorf, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Harold Alfond Center for Cancer Care

Augusta, Maine, United States

Eastern Maine Medical Center

Bangor, Maine, United States

Union Hospital of Cecil County

Elkton, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Newton-Wellesley Hospital

Newton, Massachusetts, United States

Bronson Battle Creek

Battle Creek, Michigan, United States

Spectrum Health Big Rapids Hospital

Big Rapids, Michigan, United States

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Mercy Health Mercy Campus

Muskegon, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

Metro Health Hospital

Wyoming, Michigan, United States

Minneapolis Veterans Medical Center

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Veterans Administration

Columbia, Missouri, United States

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Hematology Oncology Associates of Central New York-East Syracuse

East Syracuse, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Mission Hospital Inc-Memorial Campus

Asheville, North Carolina, United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Vidant Oncology-Kinston

Kinston, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

McLeod Regional Medical Center

Florence, South Carolina, United States

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

University of Vermont College of Medicine

Burlington, Vermont, United States

Danville Regional Medical Center

Danville, Virginia, United States

Sovah Health Martinsville

Martinsville, Virginia, United States

Countries

United States

Other Identifiers

NCI-2009-00483

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000573827

Identifier Type: -

Identifier Source: secondary_id

CALGB 50501

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-50501

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00483

Identifier Type: -

Identifier Source: org_study_id