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: January 6, 2014
Last verified: January 2014
  Purpose

This phase II clinical trial is studying how well giving lenalidomide and rituximab together works in treating patients with stage II, stage III, or stage IV follicular non-Hodgkin lymphoma. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with rituximab may kill more cancer cells.


Condition Intervention Phase
Contiguous Stage II Grade 1 Follicular Lymphoma
Contiguous Stage II Grade 2 Follicular Lymphoma
Contiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 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
Biological: rituximab
Drug: lenalidomide
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, IND#70116) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants Who Acheived 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: 66
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 oral lenalidomide once daily 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 in weeks 1, 2, 3, 4, 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity.
Biological: rituximab
Given IV
Drug: lenalidomide
Given orally

Detailed Description:

PRIMARY OBJECTIVES:

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

II. To determine the time to progression after treatment with lenalidomide and rituximab in patients with previously untreated CD20+ follicular NHL.

SECONDARY OBJECTIVES:

I. To determine the toxicity profile of this regimen in patients with previously untreated CD20+ follicular NHL.

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

III. To correlate Fcγ receptor polymorphism profiling with response to treatment with this regimen in patients with previously untreated follicular NHL.

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

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

VI. To correlate lymphoma-associated macrophages (LAM) and FOXP3, GzB, CD10, MUM1, and BCL2 expression with response to treatment with this regimen in patients with previously untreated follicular NHL.

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

OUTLINE: This is a multicenter study.

Patients receive oral lenalidomide once daily 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 in weeks 1, 2, 3, 4, 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity.

Blood, plasma, and tissue samples may be collected periodically for correlative studies.

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:

  • Histologically* confirmed follicular non-Hodgkin lymphoma (NHL)

    • WHO grade 1, 2, or 3a (> 15 centroblasts per high-power field with centrocytes present) disease
    • Stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional measurement) stage II disease
    • Previously untreated disease
  • CD20-antigen expression as confirmed by institutional flow cytometry or IHC
  • Low- or intermediate-risk disease by Follicular Lymphoma International Prognostic Index (FLIPI) (i.e., 0-2 risk factors)
  • Measurable disease on either physical examination or imaging studies

    • Any tumor mass > 1 cm is allowed
    • Non-measurable disease alone is not allowed
    • Lesions that are considered non-measurable include, but are not limited to, 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 CNS involvement by lymphoma
  • ECOG performance status 0-2
  • ANC ≥ 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Creatinine clearance ≥ 30 mL/min (unless attributable to NHL)
  • Total bilirubin ≤ 2 times upper limit of normal (unless attributable to NHL or Gilbert disease)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use two effective methods of contraception for ≥ 28 days before, during, and for ≥ 3 months after completion of study treatment
  • No history of erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome
  • No uncontrolled seizures
  • No autoimmune disorder requiring active immunosuppression
  • Patients with HIV infection are eligible, provided they meet the following criteria:

    • 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 AIDS-defining conditions
  • No evidence of active hepatitis B or C infection (i.e., no positive serology for anti-HBc or anti-HCV antibodies)

    • HBV-seropositive patients (HBsAg +) are eligible provided they are closely monitored for evidence of active HBV infection by HBV DNA testing and receive suppressive therapy with lamivudine or other HBV suppressive therapy until 6 months after the last dose of rituximab
  • No known human anti-chimeric antibody (HACA) positivity
  • Not on dialysis
  • No other concurrent investigational or non-protocol therapy for lymphoma
  • No prior systemic therapy for NHL, including chemotherapy or immunotherapy (e.g., monoclonal antibody-based therapy)

    • Prior involved-field radiotherapy allowed
  • More than 2 weeks since prior corticosteroids, except for maintenance therapy for a nonmalignant disease
  • No concurrent dexamethasone and other steroids as antiemetics
  Contacts and Locations
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
Lombardi Comprehensive Cancer Center at Georgetown University
Washington, District of Columbia, United States, 20057
United States, Florida
Florida Hospital
Orlando, Florida, United States, 32803
United States, Illinois
Saint Joseph Medical Center
Bloomington, Illinois, United States, 61701
Illinois CancerCare-Bloomington
Bloomington, Illinois, United States, 61701
Graham Hospital Association
Canton, Illinois, United States, 61520
Illinois CancerCare-Canton
Canton, Illinois, United States, 61520
Memorial Hospital
Carthage, Illinois, United States, 62321
Illinois CancerCare-Carthage
Carthage, Illinois, United States, 62321
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
University of Illinois
Chicago, Illinois, United States, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
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
Illinois CancerCare-Community Cancer Center
Normal, Illinois, United States, 61761
Community Cancer Center Foundation
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
Pekin Cancer Treatment Center
Pekin, Illinois, United States, 61554
Illinois CancerCare-Pekin
Pekin, Illinois, United States, 61603
Illinois Oncology Research Association CCOP
Peoria, Illinois, United States, 61615
OSF Saint Francis Medical Center
Peoria, Illinois, United States, 61637
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61603
Proctor Hospital
Peoria, Illinois, United States, 61614
Illinois Valley Hospital
Peru, Illinois, United States, 61354
Illinois CancerCare-Peru
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
Franklin Square Hospital Center
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, 65203
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
Saint Francis Medical Center
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
Monter Cancer Center
Lake Success, New York, United States, 11042
North Shore University Hospital
Manhasset, New York, United States, 11030
North Shore-LIJ Health System CCOP
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
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 Hospitals
Asheville, North Carolina, United States, 28801
University of North Carolina
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
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, South Carolina
McLeod Regional Medical Center
Florence, South Carolina, United States, 29506
United States, Vermont
Mountainview Medical
Berlin, Vermont, United States, 05602
University of Vermont
Burlington, Vermont, United States, 05401
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Peter Martin Cancer and Leukemia Group B
  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, U10CA031946
Study First Received: June 15, 2010
Results First Received: January 6, 2014
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 17, 2014