Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Peter Martin

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01145495
Information obtained from ClinicalTrials.gov on February 11, 2013