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Ann Arbor Stage II Grade 1 Contiguous Follicular LymphomaPhase 2NCT01145495

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

A Phase 2 study testing Laboratory Biomarker Analysis, Lenalidomide and Rituximab in people with Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma and Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma, run by National Cancer Institute (NCI) at 91 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Lenalidomide and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
91 sitesUnited States
Study dates
15 Jun 2010to 15 Jan 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 33Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

91 sites in 1 country.

91 sites in 1 country

United States91 sites

  • Randolph Hospital

    Asheboro, North Carolina, 27203

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Harold Alfond Center for Cancer Care

    Augusta, Maine, 04330

  • MedStar Franklin Square Medical Center/Weinberg Cancer Institute

    Baltimore, Maryland, 21237

  • Eastern Maine Medical Center

    Bangor, Maine, 04401

  • Central Vermont Medical Center/National Life Cancer Treatment

    Berlin Corners, Vermont, 05602

  • Walter Reed National Military Medical Center

    Bethesda, Maryland, 20889-5600

  • University of Iowa Healthcare Cancer Services Quad Cities

    Bettendorf, Iowa, 52722

  • Saint Joseph Medical Center

    Bloomington, Illinois, 61701

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • University of Vermont and State Agricultural College

    Burlington, Vermont, 05405

  • Cooper Hospital University Medical Center

    Camden, New Jersey, 08103

  • Graham Hospital Association

    Canton, Illinois, 61520

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Southeast Cancer Center

    Cape Girardeau, Missouri, 63703

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Memorial Hospital

    Carthage, Illinois, 62321

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Saint Luke's Hospital

    Chesterfield, Missouri, 63017

  • University of Illinois

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • University of Missouri - Ellis Fischel

    Columbia, Missouri, 65212

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • New Hampshire Oncology Hematology PA-Concord

    Concord, New Hampshire, 03301

  • Danville Regional Medical Center

    Danville, Virginia, 24541

  • Heartland Cancer Research NCORP

    Decatur, Illinois, 62526

  • Hematology Oncology Associates of Central New York-East Syracuse

    East Syracuse, New York, 13057

  • Christiana Care - Union Hospital

    Elkton, Maryland, 21921

  • Eureka Hospital

    Eureka, Illinois, 61530

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • Exeter Hospital

    Exeter, New Hampshire, 03833

  • McLeod Regional Medical Center

    Florence, South Carolina, 29506

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Glens Falls Hospital

    Glens Falls, New York, 12801

  • Wayne Memorial Hospital

    Goldsboro, North Carolina, 27534

  • CHI Health Saint Francis

    Grand Island, Nebraska, 68803

  • Cone Health Cancer Center

    Greensboro, North Carolina, 27403

  • East Carolina University

    Greenville, North Carolina, 27834

  • Illinois CancerCare-Havana

    Havana, Illinois, 62644

  • Mason District Hospital

    Havana, Illinois, 62644

  • Capital Region Southwest Campus

    Jefferson City, Missouri, 65109

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • Vidant Oncology-Kinston

    Kinston, North Carolina, 28501

  • AMITA Health Adventist Medical Center

    La Grange, Illinois, 60525

  • LRGHealthcare-Lakes Region General Hospital

    Laconia, New Hampshire, 03246

  • Northwell Health NCORP

    Lake Success, New York, 11042

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • Beebe Medical Center

    Lewes, Delaware, 19958

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Mcdonough District Hospital

    Macomb, Illinois, 61455

  • Solinsky Center for Cancer Care

    Manchester, New Hampshire, 03103

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Minneapolis VA Medical Center

    Minneapolis, Minnesota, 55417

  • Holy Family Medical Center

    Monmouth, Illinois, 61462

  • Illinois CancerCare-Monmouth

    Monmouth, Illinois, 61462

  • Palo Alto Medical Foundation-Camino Division

    Mountain View, California, 94040

  • Long Island Jewish Medical Center

    New Hyde Park, New York, 11040

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Bromenn Regional Medical Center

    Normal, Illinois, 61761

  • Carle Cancer Institute Normal

    Normal, Illinois, 61761

  • Illinois CancerCare-Community Cancer Center

    Normal, Illinois, 61761

  • Great Plains Health Callahan Cancer Center

    North Platte, Nebraska, 69101

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • Ottawa Regional Hospital and Healthcare Center

    Ottawa, Illinois, 61350

  • Palo Alto Medical Foundation Health Care

    Palo Alto, California, 94301

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center

    Pekin, Illinois, 61554

  • Proctor Hospital

    Peoria, Illinois, 61614

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Methodist Medical Center of Illinois

    Peoria, Illinois, 61636

  • OSF Saint Francis Medical Center

    Peoria, Illinois, 61637

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • Illinois Valley Hospital

    Peru, Illinois, 61354

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • Perry Memorial Hospital

    Princeton, Illinois, 61356

  • Annie Penn Memorial Hospital

    Reidsville, North Carolina, 27320

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Illinois CancerCare-Spring Valley

    Spring Valley, Illinois, 61362

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Center for Cancer Care and Research

    St Louis, Missouri, 63141

  • Comprehensive Cancer Care PC

    St Louis, Missouri, 63141

  • Iredell Memorial Hospital

    Statesville, North Carolina, 28677

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
Laboratory Biomarker Analysis, Lenalidomide, Rituximab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT01145495
Study groupRoleWhat they receive
Treatment (lenalidomide, rituximab)ExperimentalPatients 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.
Receives: Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At 12 months

Secondary outcomes (3)

  1. 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.

    Measured: Up to 5 years

  2. 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.

    Measured: Up to 5 years

  3. 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.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2010 (estimated)
  2. Study start15 Jun 2010
  3. Primary completion31 Dec 2012
  4. Study completion15 Jan 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01145495
Sponsor's protocol ID
NCI-2011-02047
Other IDs
NCI-2011-02047, CDR0000675161, CALGB 50803, CALGB-50803, U10CA180821, U10CA031946
Status last verified
Jun 2023
First submitted
15 Jun 2010
Last updated
27 Jun 2023

Publications

  • 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.

    PubMed 35787017

  • 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.

    PubMed 30575311

  • 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.

    PubMed 28945884

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Lenalidomide and Rituximab in people with Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma and Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma, run by National Cancer Institute (NCI) at 91 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Achieved a Complete Response (time frame: At 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01145495, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2023.

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