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

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00553644
• Other study ID #: NCI-2009-00483
• Secondary ID: NCI-2009-00483CD
• Status: Completed
• Phase: Phase 2
• Start date: November 15, 2007
• Est. completion date: January 21, 2014

Study information

• Verified date: October 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: January 21, 2014
• Est. primary completion date: December 31, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Recurrent Mantle Cell Lymphoma

Intervention

Drug:
• Bortezomib
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lenalidomide
Given PO

Locations

Country	Name	City	State
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Mission Hospital Inc-Memorial Campus	Asheville	North Carolina
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Graham Hospital Association	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Veterans Administration	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	Eureka Hospital	Eureka	Illinois
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
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	Wayne Memorial Hospital	Goldsboro	North Carolina
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	Kaiser Permanente - Harbor City	Harbor City	California
United States	Hartford Hospital	Hartford	Connecticut
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente-Cadillac	Los Angeles	California
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Minneapolis Veterans Medical Center	Minneapolis	Minnesota
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Mercy Health Mercy Campus	Muskegon	Michigan
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Newton-Wellesley Hospital	Newton	Massachusetts
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	Kaiser Permanente - Panorama City	Panorama City	California
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Proctor Hospital	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	Kaiser Permanente-Riverside	Riverside	California
United States	Washington University School of Medicine	Saint Louis	Missouri
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	Saint Margaret's Hospital	Spring Valley	Illinois
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Munson Medical Center	Traverse City	Michigan
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	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