Rituximab and Dexamethasone in Treating Patients With Low-Grade Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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This phase II trial studies the side effects and how well giving rituximab and dexamethasone together works in treating patients with low-grade non-Hodgkin lymphoma (NHL). 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. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with dexamethasone may kill more cancer cells

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate clinical response rate (RR) at 3 and 6 months. II. To estimate Grade 2-4 -infusion-related toxicity. SECONDARY OBJECTIVES: I. To evaluate laboratory parameters and correlate with clinical response including: antibody dependent cell mediated cytotoxicity and effector cell phenotype analysis at baseline, 4 weeks and three months. II. To evaluate laboratory parameters and correlate with clinical response including: soluble cluster of differentiation (CD)20 fragments or CD20-containing membrane fragments at baseline, 4 weeks, and 3 months. III. To evaluate laboratory parameters and correlate with clinical response including: phenotype analysis of CD16 and CD32 on natural killer (NK) cells. IV. To evaluate laboratory parameters and correlate with clinical response including: rituximab pharmacokinetic studies at baseline, 4 weeks and 3 months. OUTLINE: Patients receive dexamethasone intravenously (IV) and rituximab IV once weekly. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 and 6 months.

Official Title
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Rituximab and Dexamethasone in CD20 Positive Low Grade and Follicular Non-Hodgkin's Lymphoma

Conditions
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Contiguous Stage II Grade 1 Follicular Lymphoma, Contiguous Stage II Grade 2 Follicular Lymphoma, Contiguous Stage II Marginal Zone Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Marginal Zone Lymphoma, Splenic Marginal Zone Lymphoma, Stage I Grade 1 Follicular Lymphoma, Stage I Grade 2 Follicular Lymphoma, Stage I Marginal Zone Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Marginal Zone Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Marginal Zone Lymphoma, Waldenstrom Macroglobulinemia

Intervention / Treatment
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* Other: pharmacological study
* Biological: rituximab
* Drug: dexamethasone
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically proven CD20+ low grade B cell lymphoma including follicular, marginal zone, monocytoid B cell, and lymphoplasmacytoid lymphoma; patients may be previously untreated or in relapse Patients must have measurable disease with clearly defined margins assessed by physical exam with direct measurement (for cutaneous B-cell lymphomas), computed tomography (CT) or magnetic resonance imaging (MRI), defined as >= 20 mm with conventional CT or MRI or >= 10 mm using spiral CT scan Absolute neutrophil count >= 1000/mm^3 Hemoglobin > 7 g/dl Platelets >= 100,000/mm^3 Serum creatinine =< 2.5 mg/dl Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2x the upper limit of normal (ULN) Karnofsky performance score >= 70 % Patient has signed an Institutional Review Board (IRB) approved informed consent form that conforms to federal and institutional guidelines Exclusion Criteria: Patient has received rituximab therapy within 6 months of entry into protocol Patient has received systemic steroid therapy within one month of entry into protocol Patient has Intermediate or High Grade NHL, mantle cell lymphoma, chronic lymphocytic leukemia, or small lymphocytic lymphoma Patient is pregnant or lactating Patient is unwilling or unable to practice contraception during treatment and for one year thereafter Patient has active central nervous system (CNS) disease Patient has human immunodeficiency virus (HIV) disease Patient has an active infection requiring antimicrobial therapy Patient has significant heart disease, New York Heart Classification III or IV heart disease (III: Marked limitation of physical activity; comfortable at rest, but less than ordinary activity causes fatigue, or dyspnea; IV: Unable to carry on any physical activity without symptoms; symptoms are present even at rest; if any physical activity is undertaken, symptoms are increased) Patient requires supplemental oxygen Patient has a concomitant malignancy or previous malignancy within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, or in situ cervical or in situ breast cancer Patients with active hepatitis B virus (HBV) infection or hepatitis, or with hepatitis C positive serology

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: No previous treatment<br>Patients received no previous treatment. Patients enrolled in the trial received dexamethasone IV and rituximab IV once weekly. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity. | Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Biological: rituximab<br>* Given IV<br>* Other names: Rituxan;Drug: dexamethasone<br>* Given IV<br>* Other names: DXM;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Other: Previous treatment<br>Patients received previous treatment. Patients enrolled in the trial received dexamethasone IV and rituximab IV once weekly. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity. | Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Biological: rituximab<br>* Given IV<br>* Other names: Rituxan;Drug: dexamethasone<br>* Given IV<br>* Other names: DXM;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Survival without measurable progression of lymphoma estimated according to the Kaplan-Meier method | At 3 and 6 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Percentage of patients remaining alive estimated according to the Kaplan-Meier method | At 6 months, 12 months and 24 months after enrollment |