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

NCT ID: NCT01145495

Last Updated: 2023-06-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-15

Study Completion Date

2022-01-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (lenalidomide, rituximab)

Patients receive lenalidomide PO 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 IV on days 1, 8, 15, and 22 and in weeks 13, 21, 29, and 37 in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Lenalidomide

Intervention Type DRUG

Given PO

Rituximab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Lenalidomide

Given PO

Intervention Type DRUG

Rituximab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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CC-5013 CC5013 CDC 501 Revlimid ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Riabni Rituxan Rituximab ABBS Rituximab ARRX Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar JHL1101 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 Rituximab Biosimilar SIBP-02 rituximab biosimilar TQB2303 Rituximab PVVR rituximab-abbs Rituximab-arrx Rituximab-pvvr RTXM83 Ruxience Truxima

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter Martin

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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Palo Alto Medical Foundation-Camino Division

Mountain View, California, United States

Site Status

Palo Alto Medical Foundation Health Care

Palo Alto, California, United States

Site Status

Beebe Medical Center

Lewes, Delaware, United States

Site Status

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Saint Joseph Medical Center

Bloomington, Illinois, United States

Site Status

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Site Status

Graham Hospital Association

Canton, Illinois, United States

Site Status

Illinois CancerCare-Canton

Canton, Illinois, United States

Site Status

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Site Status

Memorial Hospital

Carthage, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Heartland Cancer Research NCORP

Decatur, Illinois, United States

Site Status

Eureka Hospital

Eureka, Illinois, United States

Site Status

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Site Status

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Site Status

Illinois CancerCare-Havana

Havana, Illinois, United States

Site Status

Mason District Hospital

Havana, Illinois, United States

Site Status

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Site Status

AMITA Health Adventist Medical Center

La Grange, Illinois, United States

Site Status

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Site Status

Mcdonough District Hospital

Macomb, Illinois, United States

Site Status

Holy Family Medical Center

Monmouth, Illinois, United States

Site Status

Illinois CancerCare-Monmouth

Monmouth, Illinois, United States

Site Status

Bromenn Regional Medical Center

Normal, Illinois, United States

Site Status

Carle Cancer Institute Normal

Normal, Illinois, United States

Site Status

Illinois CancerCare-Community Cancer Center

Normal, Illinois, United States

Site Status

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Site Status

Ottawa Regional Hospital and Healthcare Center

Ottawa, Illinois, United States

Site Status

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Site Status

OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center

Pekin, Illinois, United States

Site Status

Proctor Hospital

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peru

Peru, Illinois, United States

Site Status

Illinois Valley Hospital

Peru, Illinois, United States

Site Status

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Site Status

Perry Memorial Hospital

Princeton, Illinois, United States

Site Status

Illinois CancerCare-Spring Valley

Spring Valley, Illinois, United States

Site Status

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

Site Status

University of Iowa Healthcare Cancer Services Quad Cities

Bettendorf, Iowa, United States

Site Status

Harold Alfond Center for Cancer Care

Augusta, Maine, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

MedStar Franklin Square Medical Center/Weinberg Cancer Institute

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Site Status

Christiana Care - Union Hospital

Elkton, Maryland, United States

Site Status

Minneapolis VA Medical Center

Minneapolis, Minnesota, United States

Site Status

Southeast Cancer Center

Cape Girardeau, Missouri, United States

Site Status

Saint Luke's Hospital

Chesterfield, Missouri, United States

Site Status

University of Missouri - Ellis Fischel

Columbia, Missouri, United States

Site Status

Capital Region Southwest Campus

Jefferson City, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

Center for Cancer Care and Research

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Care PC

St Louis, Missouri, United States

Site Status

CHI Health Saint Francis

Grand Island, Nebraska, United States

Site Status

Great Plains Health Callahan Cancer Center

North Platte, Nebraska, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

New Hampshire Oncology Hematology PA-Concord

Concord, New Hampshire, United States

Site Status

Exeter Hospital

Exeter, New Hampshire, United States

Site Status

LRGHealthcare-Lakes Region General Hospital

Laconia, New Hampshire, United States

Site Status

Solinsky Center for Cancer Care

Manchester, New Hampshire, United States

Site Status

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Site Status

Hematology Oncology Associates of Central New York-East Syracuse

East Syracuse, New York, United States

Site Status

Glens Falls Hospital

Glens Falls, New York, United States

Site Status

Northwell Health NCORP

Lake Success, New York, United States

Site Status

Northwell Health/Center for Advanced Medicine

Lake Success, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status

State University of New York Upstate Medical University

Syracuse, New York, United States

Site Status

Randolph Hospital

Asheboro, North Carolina, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Site Status

Cone Health Cancer Center

Greensboro, North Carolina, United States

Site Status

East Carolina University

Greenville, North Carolina, United States

Site Status

Vidant Oncology-Kinston

Kinston, North Carolina, United States

Site Status

Annie Penn Memorial Hospital

Reidsville, North Carolina, United States

Site Status

Iredell Memorial Hospital

Statesville, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

McLeod Regional Medical Center

Florence, South Carolina, United States

Site Status

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

Site Status

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Site Status

Danville Regional Medical Center

Danville, Virginia, United States

Site Status

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Rutherford SC, Yin J, Pederson L, Perez Burbano G, LaPlant B, Shadman M, Li H, LeBlanc ML, Kenkre VP, Hong F, Blum KA, Dockter T, Martin P, Jung SH, Grant B, Rosenbaum C, Ujjani C, Barr PM, Unger JM, Cheson BD, Bartlett NL, Kahl B, Friedberg JW, Mandrekar SJ, Leonard JP. Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials. J Clin Oncol. 2023 Jan 10;41(2):336-342. doi: 10.1200/JCO.21.02301. Epub 2022 Jul 5.

Reference Type DERIVED
PMID: 35787017 (View on PubMed)

Lansigan F, Barak I, Pitcher B, Jung SH, Cheson BD, Czuczman M, Martin P, Hsi E, Schoder H, Smith S, Bartlett NL, Leonard JP, Blum KA. The prognostic significance of PFS24 in follicular lymphoma following firstline immunotherapy: A combined analysis of 3 CALGB trials. Cancer Med. 2019 Jan;8(1):165-173. doi: 10.1002/cam4.1918. Epub 2018 Dec 21.

Reference Type DERIVED
PMID: 30575311 (View on PubMed)

Martin P, Jung SH, Pitcher B, Bartlett NL, Blum KA, Shea T, Hsi ED, Ruan J, Smith SE, Leonard JP, Cheson BD. A phase II trial of lenalidomide plus rituximab in previously untreated follicular non-Hodgkin's lymphoma (NHL): CALGB 50803 (Alliance). Ann Oncol. 2017 Nov 1;28(11):2806-2812. doi: 10.1093/annonc/mdx496.

Reference Type DERIVED
PMID: 28945884 (View on PubMed)

Other Identifiers

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NCI-2011-02047

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000675161

Identifier Type: -

Identifier Source: secondary_id

CALGB 50803

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-50803

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02047

Identifier Type: -

Identifier Source: org_study_id

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