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: April 18, 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 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 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
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

  Show 79 Study Locations
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: April 18, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 16, 2014