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

A Phase II Trial of Bortezomib (NSC #681239) + Lenalidomide (Revlimid™, CC-5013) (NSC #703813) for Relapsed/Refractory Mantle Cell Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Mantle Cell Lymphoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Drug: Bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92806
      • Kaiser Permanente-Anaheim
    • Baldwin Park, California, United States, 91706
      • Kaiser Permanente-Baldwin Park
    • Bellflower, California, United States, 90706
      • Kaiser Permanente-Bellflower
    • Fontana, California, United States, 92335
      • Kaiser Permanente-Fontana
    • Harbor City, California, United States, 90710
      • Kaiser Permanente - Harbor City
    • Irvine, California, United States, 92618
      • Kaiser Permanente-Irvine
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90034
      • Kaiser Permanente-Cadillac
    • Panorama City, California, United States, 91402
      • Kaiser Permanente - Panorama City
    • Riverside, California, United States, 92505
      • Kaiser Permanente-Riverside
    • San Diego, California, United States, 92120
      • Kaiser Permanente-San Diego Zion
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
    • San Marcos, California, United States, 92078
      • Kaiser Permanente-San Marcos
    • Woodland Hills, California, United States, 91367
      • Kaiser Permanente-Woodland Hills
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Illinois
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Decatur, Illinois, United States, 62526
      • Heartland Cancer Research NCORP
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex - Hospital
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Pekin, Illinois, United States, 61554
      • Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • Saint Margaret's Hospital
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
  • Iowa
    • Bettendorf, Iowa, United States, 52722
      • University of Iowa Healthcare Cancer Services Quad Cities
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
  • Maryland
    • Elkton, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Newton, Massachusetts, United States, 02462
      • Newton-Wellesley Hospital
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Big Rapids, Michigan, United States, 49307
      • Spectrum Health Big Rapids Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Grand Rapids, Michigan, United States, 49503
      • Cancer Research Consortium of West Michigan NCORP
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota/Masonic Cancer Center
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis Veterans Medical Center
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri - Ellis Fischel
    • Columbia, Missouri, United States, 65201
      • Veterans Administration
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • East Syracuse, New York, United States, 13057
      • Hematology Oncology Associates of Central New York-East Syracuse
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital Inc-Memorial Campus
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Novant Health Presbyterian Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Kinston, North Carolina, United States, 28501
      • Vidant Oncology-Kinston
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
  • South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05405
      • University of Vermont College of Medicine
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Martinsville, Virginia, United States, 24115
      • Sovah Health Martinsville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013; Revlimid; CC5013; CDC 501; Drug: Bortezomib; Given IV; Other Names: Velcade; MLN341; PS-341; LDP 341; [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid; PS341

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With an Overall Response Defined as Complete Response and Partial Response	Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease.	Duration of treatment (assessed up to 6 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Number of participants who experienced a maximum grade 3, 4 or 5 adverse event. The grading scales found in the revised NCI CTCAE version 4.0 was utilized for adverse event reporting	Duration of Treatment (up to 6 years)
Time to Progression	Time to progression (TTP) is defined as the time from study entry until progression or death due to any cause. The median TTP with 95% CI was estimated using the Kaplan-Meier method.	Assessed up to 6 years
Overall Survival	Overall survival (OS) is defined as the time from study entry until death. The median OS with 95% CI was estimated using the Kaplan-Meier method..	Assessed up to 6 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Vicki Morrison, Alliance for Clinical Trials in Oncology

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2007
• Primary Completion (Actual): December 31, 2012
• Study Completion (Actual): January 21, 2014

Study Registration Dates

• First Submitted: November 2, 2007
• First Submitted That Met QC Criteria: November 2, 2007
• First Posted (Estimate): November 4, 2007

Study Record Updates

• Last Update Posted (Actual): October 30, 2018
• Last Update Submitted That Met QC Criteria: October 2, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Bortezomib
• Other Study ID Numbers: NCI-2009-00483 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000573827; CALGB 50501 (Other Identifier: Alliance for Clinical Trials in Oncology); CALGB-50501 (Other Identifier: CTEP)