Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

Ann Arbor Stage III Grade 2 Follicular Lymphoma Clinical Trial

Official title:

A Phase II Trial of Lenalidomide (Revlimid (TM), CC-5013) (NSC #703813) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01145495
• Other study ID #: NCI-2011-02047
• Secondary ID: NCI-2011-02047CD
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2010
• Est. completion date: January 15, 2022

Study information

• Verified date: June 2023
• 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 lenalidomide and rituximab work in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide together with rituximab may kill more cancer cells.

Description:

PRIMARY OBJECTIVES:

I. To determine the response rate (overall and complete) to lenalidomide + rituximab in follicular non-Hodgkin lymphoma (NHL) patients who have received no prior systemic therapy.

II. To determine the time to progression after lenalidomide + rituximab in previously untreated patients with cluster of differentiation (CD)20+ follicular NHL.

SECONDARY OBJECTIVES:

I. To determine the toxicity profile of lenalidomide + rituximab therapy in previously untreated patients with CD20+ follicular NHL.

II. To establish whether the therapeutic effects of lenalidomide + rituximab combination are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone).

III. To correlate fragment crystallizable gamma (Fcg) receptor polymorphism profiling with response to lenalidomide + rituximab in previously untreated patients with follicular NHL.

IV. To determine the impact of lenalidomide on immune parameters in patients with previously untreated follicular lymphoma.

V. To determine the impact of lenalidomide on angiogenic parameters in patients with previously untreated follicular lymphoma.

VI. To correlate lymphoma-associated macrophages (LAM) and forkhead box P3 (FOXP3), granzyme B (GzB), CD10, multiple myeloma oncogene 1 (MUM1), and B-cell lymphoma 2 (BCL2) expression with response to rituximab + lenalidomide in previously untreated patients with follicular lymphoma.

VII. Determine whether immune gene signatures previously identified as prognostic factors in follicular lymphoma (FL) can be applied to paraffin-embedded tissues in rituximab treated patients; evaluate micro ribonucleic acid (RNA) signatures associated with these gene signatures and outcome; to validate immunohistochemical markers associated with outcome in FL (CD68 LAMs, FOXP3, CD10, BCL6, FOXP1, MUM1); and investigate whether markers of angiogenesis may be of value in prognosis of FL.

OUTLINE:

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 and on weeks 13, 21, 29, and 37 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 2 years and then every 6 months for up to 8 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: January 15, 2022
• Est. primary completion date: December 31, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Previously untreated, histologically confirmed follicular lymphoma, World Health Organization (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass >= 7 cm in any uni-dimensional measurement) stage II

• 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 for diagnosis

• 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 CD20 antigen expression

• Low or intermediate risk by Follicular Lymphoma International Prognostic Index (FLIPI): 0-2 risk factors

• No prior systemic therapy for NHL, including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy); patients may have received involved-field radiation therapy

• No corticosteroids within two weeks prior to study entry, except for maintenance therapy for a non-malignant disease

• Eastern Cooperative Oncology Group (ECOG) performance status =< 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 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/pulmonis

• Bone marrow (involvement by NHL 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

• No evidence of coinfection with hepatitis B or C

• CD4+ cell count >= 400/mm^3

• No evidence of resistant strains of HIV

• If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL

• If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL

• No history of acquired immune deficiency syndrome (AIDS)-defining conditions

• No evidence of active hepatitis B or C infection (i.e., no positive serology for anti-hepatitis B core [HBc] or anti-hepatitis C virus [HCV] antibodies); hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen positive [HBsAg +]) are eligible if they are closely monitored for evidence of active HBV infection by HBV deoxyribonucleic acid (DNA) testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last rituximab dose

• Patients with a history of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome are not eligible

• Patients with uncontrolled seizures are not eligible

• Patients with an autoimmune disorder requires active immunosuppression are not eligible

• 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 preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure

• No known human anti-chimeric antibody (HACA) positivity

• Absolute neutrophil count (ANC) >= 1,000/microliter

• Platelet count >= 75,000/microliter

• Creatinine clearance >= 30 mL/min unless attributable to NHL; to be calculated by method of Cockcroft-Gault, using actual weight; maximum creatinine clearance (CrCl) 125 mL/min

• Total bilirubin =< 2 times upper limit of normal (ULN) unless attributable to NHL or Gilbert disease

Related Conditions & MeSH terms

• Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma
• Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma
• Ann Arbor Stage II Grade 2 Contiguous Follicular Lymphoma
• Ann Arbor Stage II Grade 2 Non-Contiguous Follicular Lymphoma
• Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma
• Ann Arbor Stage II Grade 3 Non-Contiguous Follicular Lymphoma
• Ann Arbor Stage III Grade 1 Follicular Lymphoma
• Ann Arbor Stage III Grade 2 Follicular Lymphoma
• Ann Arbor Stage III Grade 3 Follicular Lymphoma
• Ann Arbor Stage IV Grade 1 Follicular Lymphoma
• Ann Arbor Stage IV Grade 2 Follicular Lymphoma
• Ann Arbor Stage IV Grade 3 Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lenalidomide
Given PO

Biological:
• Rituximab
Given IV

Locations

Country	Name	City	State
United States	Randolph Hospital	Asheboro	North Carolina
United States	Mission Hospital	Asheville	North Carolina
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	University of Iowa Healthcare Cancer Services Quad Cities	Bettendorf	Iowa
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
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	Christiana Care - Union Hospital	Elkton	Maryland
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Exeter Hospital	Exeter	New Hampshire
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Glens Falls Hospital	Glens Falls	New York
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	AMITA Health Adventist Medical Center	La Grange	Illinois
United States	LRGHealthcare-Lakes Region General Hospital	Laconia	New Hampshire
United States	Northwell Health NCORP	Lake Success	New York
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Beebe Medical Center	Lewes	Delaware
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	North Shore University Hospital	Manhasset	New York
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	Great Plains Health Callahan Cancer Center	North Platte	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	AdventHealth Orlando	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Annie Penn Memorial Hospital	Reidsville	North Carolina
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Center for Cancer Care and Research	Saint Louis	Missouri
United States	Comprehensive Cancer Care PC	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

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 Who Achieved a Complete Response	Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.	At 12 months
Secondary	Toxicity of Study Treatment, Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	Data will be summarized using frequency tables.	Up to 5 years
Secondary	Disease Progression	Kaplan-Meier method will be used. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Up to 5 years
Secondary	Best Response	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 5 years