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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01145495
First received: June 15, 2010
Last updated: June 4, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Stage II Grade 1 Contiguous Follicular Lymphoma
Stage II Grade 1 Non-Contiguous Follicular Lymphoma
Stage II Grade 2 Contiguous Follicular Lymphoma
Stage II Grade 2 Non-Contiguous Follicular Lymphoma
Stage II Grade 3 Contiguous Follicular Lymphoma
Stage II Grade 3 Non-Contiguous Follicular Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Biological: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Lenalidomide (Revlimid (TM), CC-5013) (NSC #703813) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Participants Who Achieved a Complete Response [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
    Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.


Secondary Outcome Measures:
  • Toxicity of Study Treatment, Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Data will be summarized using frequency tables.

  • Time to Disease Progression [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Time to Best Response [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.


Enrollment: 63
Study Start Date: June 2010
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • LENALIDOMIDE
  • Revlimid
Biological: Rituximab
Given IV
Other Names:
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • RITUXIMAB
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • RTXM83

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01145495

  Hide Study Locations
Locations
United States, Delaware
Beebe Medical Center
Lewes, Delaware, United States, 19958
Christiana Care Health System-Christiana Hospital
Newark, Delaware, United States, 19718
United States, District of Columbia
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
Florida Hospital Orlando
Orlando, Florida, United States, 32803
United States, Illinois
Illinois CancerCare-Bloomington
Bloomington, Illinois, United States, 61704
Saint Joseph Medical Center
Bloomington, Illinois, United States, 61701
Graham Hospital Association
Canton, Illinois, United States, 61520
Illinois CancerCare-Canton
Canton, Illinois, United States, 61520
Illinois CancerCare-Carthage
Carthage, Illinois, United States, 62321
Memorial Hospital
Carthage, Illinois, United States, 62321
University of Illinois
Chicago, Illinois, United States, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Eureka Hospital
Eureka, Illinois, United States, 61530
Illinois CancerCare-Eureka
Eureka, Illinois, United States, 61530
Illinois CancerCare Galesburg
Galesburg, Illinois, United States, 61401
Illinois CancerCare-Havana
Havana, Illinois, United States, 62644
Mason District Hospital
Havana, Illinois, United States, 62644
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, United States, 61443
Illinois CancerCare-Macomb
Macomb, Illinois, United States, 61455
Mcdonough District Hospital
Macomb, Illinois, United States, 61455
Illinois CancerCare-Monmouth
Monmouth, Illinois, United States, 61462
Holy Family Medical Center
Monmouth, Illinois, United States, 61462
Bromenn Regional Medical Center
Normal, Illinois, United States, 61761
Community Cancer Center Foundation
Normal, Illinois, United States, 61761
Illinois CancerCare-Community Cancer Center
Normal, Illinois, United States, 61761
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, United States, 61350
Ottawa Regional Hospital and Healthcare Center
Ottawa, Illinois, United States, 61350
Illinois CancerCare-Pekin
Pekin, Illinois, United States, 61554
Pekin Cancer Treatment Center
Pekin, Illinois, United States, 61554
Proctor Hospital
Peoria, Illinois, United States, 61614
Illinois Oncology Research Association CCOP
Peoria, Illinois, United States, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61603
OSF Saint Francis Medical Center
Peoria, Illinois, United States, 61637
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Illinois CancerCare-Peru
Peru, Illinois, United States, 61354
Illinois Valley Hospital
Peru, Illinois, United States, 61354
Illinois CancerCare-Princeton
Princeton, Illinois, United States, 61356
Perry Memorial Hospital
Princeton, Illinois, United States, 61356
Illinois CancerCare-Spring Valley
Spring Valley, Illinois, United States, 61362
United States, Iowa
Hematology Oncology Associates-Quad Cities
Bettendorf, Iowa, United States, 52722
United States, Maine
Harold Alfond Center for Cancer Care
Augusta, Maine, United States, 04330
Eastern Maine Medical Center
Bangor, Maine, United States, 04401
United States, Maryland
MedStar Franklin Square Medical Center/Weinberg Cancer Institute
Baltimore, Maryland, United States, 21237
Walter Reed National Military Medical Center
Bethesda, Maryland, United States, 20889-5600
Union Hospital of Cecil County
Elkton MD, Maryland, United States, 21921
United States, Missouri
Southeast Cancer Center
Cape Girardeau, Missouri, United States, 63703
University of Missouri - Ellis Fischel
Columbia, Missouri, United States, 65212
Capital Region Medical Center-Goldschmidt Cancer Center
Jefferson City, Missouri, United States, 65109
Center for Cancer Care and Research
Saint Louis, Missouri, United States, 63141
Comprehensive Cancer Care PC
Saint Louis, Missouri, United States, 63141
Missouri Baptist Medical Center
Saint Louis, Missouri, United States, 63131
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
CHI Health Saint Francis
Grand Island, Nebraska, United States, 68803
Great Plains Regional Medical Center
North Platte, Nebraska, United States, 69103
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Exeter Hospital
Exeter, New Hampshire, United States, 03833
United States, New Jersey
Cooper Hospital University Medical Center
Camden, New Jersey, United States, 08103
United States, New York
Glens Falls Hospital
Glens Falls, New York, United States, 12801
North Shore University Hospital
Manhasset, New York, United States, 11030
North Shore-LIJ Health System NCORP
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
North Shore-LIJ Health System/Center for Advanced Medicine
New Hyde Park, New York, United States, 11040
Weill Medical College of Cornell University
New York, New York, United States, 10065
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
Randolph Hospital
Asheboro, North Carolina, United States, 27203
Mission Hospital-Memorial Campus
Asheville, North Carolina, United States, 28801
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Wayne Memorial Hospital
Goldsboro, North Carolina, United States, 27534
Cone Health Cancer Center
Greensboro, North Carolina, United States, 27403
East Carolina University
Greenville, North Carolina, United States, 27858
Annie Penn Memorial Hospital
Reidsville, North Carolina, United States, 27320
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, South Carolina
McLeod Regional Medical Center
Florence, South Carolina, United States, 29506
United States, Vermont
Central Vermont Medical Center/National Life Cancer Treatment
Berlin, Vermont, United States, 05602
University of Vermont College of Medicine
Burlington, Vermont, United States, 05405
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Peter Martin Alliance for Clinical Trials in Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01145495     History of Changes
Other Study ID Numbers: NCI-2011-02047, NCI-2011-02047, CDR0000675161, CALGB 50803, CALGB-50803, U10CA180821, U10CA031946
Study First Received: June 15, 2010
Results First Received: January 6, 2014
Last Updated: June 4, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Antibodies
Antibodies, Monoclonal
Lenalidomide
Rituximab
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antirheumatic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015