Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
- Conditions
- Recurrent Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT00553644
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
-
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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (bortezomib, lenalidomide) Laboratory Biomarker Analysis 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. Treatment (bortezomib, lenalidomide) Bortezomib 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. Treatment (bortezomib, lenalidomide) 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.
- Primary Outcome Measures
Name Time Method Number of Participants With an Overall Response Defined as Complete Response and Partial Response Duration of treatment (assessed up to 6 years) 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.
- Secondary Outcome Measures
Name Time Method Incidence of Adverse Events Duration of Treatment (up to 6 years) 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
Time to Progression Assessed up to 6 years 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.
Overall Survival Assessed up to 6 years 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..
Trial Locations
- Locations (82)
Kaiser Permanente-Irvine
🇺🇸Irvine, California, United States
Kaiser Permanente-Riverside
🇺🇸Riverside, California, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Galesburg Cottage Hospital
🇺🇸Galesburg, Illinois, United States
Fort Wayne Medical Oncology and Hematology Inc-Parkview
🇺🇸Fort Wayne, Indiana, United States
Mission Hospital Inc-Memorial Campus
🇺🇸Asheville, North Carolina, United States
Vidant Oncology-Kinston
🇺🇸Kinston, North Carolina, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Vermont College of Medicine
🇺🇸Burlington, Vermont, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Kaiser Permanente-San Diego Mission
🇺🇸San Diego, California, United States
Kaiser Permanente-San Diego Zion
🇺🇸San Diego, California, United States
Minneapolis Veterans Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
Kaiser Permanente Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Baldwin Park
🇺🇸Baldwin Park, California, United States
Kaiser Permanente-Fontana
🇺🇸Fontana, California, United States
Graham Hospital Association
🇺🇸Canton, Illinois, United States
Heartland Cancer Research NCORP
🇺🇸Decatur, Illinois, United States
Eureka Hospital
🇺🇸Eureka, Illinois, United States
Harold Alfond Center for Cancer Care
🇺🇸Augusta, Maine, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
🇺🇸Pekin, Illinois, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
Cancer Research Consortium of West Michigan NCORP
🇺🇸Grand Rapids, Michigan, United States
Veterans Administration
🇺🇸Columbia, Missouri, United States
Danville Regional Medical Center
🇺🇸Danville, Virginia, 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
Metro Health Hospital
🇺🇸Wyoming, Michigan, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Kaiser Permanente-Cadillac
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Anaheim
🇺🇸Anaheim, California, United States
Kaiser Permanente-Bellflower
🇺🇸Bellflower, California, United States
Kaiser Permanente - Harbor City
🇺🇸Harbor City, California, United States
Kaiser Permanente - Panorama City
🇺🇸Panorama City, California, United States
Kaiser Permanente-San Marcos
🇺🇸San Marcos, California, United States
Kaiser Permanente-Woodland Hills
🇺🇸Woodland Hills, California, United States
Beebe Medical Center
🇺🇸Lewes, Delaware, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Christiana Care Health System-Christiana Hospital
🇺🇸Newark, Delaware, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Hopedale Medical Complex - Hospital
🇺🇸Hopedale, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Bromenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Mcdonough District Hospital
🇺🇸Macomb, Illinois, United States
Community Cancer Center Foundation
🇺🇸Normal, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Pekin Hospital
🇺🇸Pekin, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
Illinois Valley Hospital
🇺🇸Peru, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Saint Margaret's Hospital
🇺🇸Spring Valley, Illinois, United States
Newton-Wellesley Hospital
🇺🇸Newton, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Bronson Battle Creek
🇺🇸Battle Creek, Michigan, United States
Mercy Health Saint Mary's
🇺🇸Grand Rapids, Michigan, United States
Mercy Health Mercy Campus
🇺🇸Muskegon, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, 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
Wayne Memorial Hospital
🇺🇸Goldsboro, North Carolina, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Novant Health Presbyterian Medical Center
🇺🇸Charlotte, North Carolina, United States
McLeod Regional Medical Center
🇺🇸Florence, South Carolina, United States
Central Vermont Medical Center/National Life Cancer Treatment
🇺🇸Berlin, Vermont, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Spectrum Health Big Rapids Hospital
🇺🇸Big Rapids, Michigan, United States
Sovah Health Martinsville
🇺🇸Martinsville, Virginia, United States