Clinical trial NCT00553644: Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
Official title: A Phase II Trial of Bortezomib (NSC #681239) + Lenalidomide (Revlimid™, CC-5013) (NSC #703813) for Relapsed/Refractory Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Mantle Cell Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-11-04
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With an Overall Response Defined as Complete Response and Partial Response
timeFrame: Duration of treatment (assessed up to 6 years)
Secondary outcomes:
measure: Incidence of Adverse Events
timeFrame: Duration of Treatment (up to 6 years)
measure: Time to Progression
timeFrame: Assessed up to 6 years
measure: Overall Survival
timeFrame: Assessed up to 6 years
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Kaiser Permanente-Anaheim
state: California
city: Baldwin Park
country: United States
facility: Kaiser Permanente-Baldwin Park
state: California
city: Bellflower
country: United States
facility: Kaiser Permanente-Bellflower
state: California
city: Fontana
country: United States
facility: Kaiser Permanente-Fontana
state: California
city: Harbor City
country: United States
facility: Kaiser Permanente - Harbor City
state: California
city: Irvine
country: United States
facility: Kaiser Permanente-Irvine
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente-Cadillac
state: California
city: Panorama City
country: United States
facility: Kaiser Permanente - Panorama City
state: California
city: Riverside
country: United States
facility: Kaiser Permanente-Riverside
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-San Diego Mission
state: California
city: San Diego
country: United States
facility: Kaiser Permanente-San Diego Zion
state: California
city: San Marcos
country: United States
facility: Kaiser Permanente-San Marcos
state: California
city: Woodland Hills
country: United States
facility: Kaiser Permanente-Woodland Hills
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Heartland Cancer Research NCORP
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Galesburg
country: United States
facility: Illinois CancerCare-Galesburg
state: Illinois
city: Galesburg
country: United States
facility: Western Illinois Cancer Treatment Center
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex - Hospital
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center Foundation
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Peru
country: United States
facility: Valley Radiation Oncology
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Saint Margaret's Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: Bettendorf
country: United States
facility: University of Iowa Healthcare Cancer Services Quad Cities
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Augusta
country: United States
facility: Harold Alfond Center for Cancer Care
state: Maine
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: Newton-Wellesley Hospital
state: Massachusetts
city: Battle Creek
country: United States
facility: Bronson Battle Creek
state: Michigan
city: Big Rapids
country: United States
facility: Spectrum Health Big Rapids Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer Research Consortium of West Michigan NCORP
state: Michigan
city: Grand Rapids
country: United States
facility: Mercy Health Saint Mary's
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health at Butterworth Campus
state: Michigan
city: Muskegon
country: United States
facility: Mercy Health Mercy Campus
state: Michigan
city: Traverse City
country: United States
facility: Munson Medical Center
state: Michigan
city: Wyoming
country: United States
facility: Metro Health Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Veterans Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Columbia
country: United States
facility: Veterans Administration
state: Missouri
city: Columbia
country: United States
facility: University of Missouri - Ellis Fischel
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York-East Syracuse
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Asheville
country: United States
facility: Mission Hospital Inc-Memorial Campus
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Kinston
country: United States
facility: Vidant Oncology-Kinston
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Martinsville
country: United States
facility: Sovah Health Martinsville
state: Virginia
Study officials:
affiliation: Alliance for Clinical Trials in Oncology
name: Vicki Morrison
role: PRINCIPAL_INVESTIGATOR
References: