Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone 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 pegfilgrastim together with rituximab works in treating patients with untreated, relapsed, or refractory follicular lymphoma, small lymphocytic lymphoma (SLL), or marginal zone lymphoma (MZL). Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of therapy. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or tumor cancer-killing substances to them. Giving pegfilgrastim together with rituximab may kill more cancer cells

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the safety of Pegfilgrastim in combination with rituximab in patients with untreated or relapsed/refractory follicular, SLL or MZL. SECONDARY OBJECTIVES: I. To evaluate the efficacy (including overall response rate and durability of objective responses) of Pegfilgrastim in combination with rituximab in patients with untreated or relapsed/refractory follicular, SLL or MZL. II. To evaluate functional and phenotypic characteristics of host neutrophils undergoing treatment with Pegfilgrastim and rituximab. III. To evaluate changes in cluster of differentiation (CD)20 antigen expression and density of expression in patients receiving Pegfilgrastim and rituximab. IV. To evaluate changes in serum levels of tumor necrosis factor (TNF), interferon alpha (INFalpha) and free radical levels in patients undergoing treatment with Pegfilgrastim and rituximab. OUTLINE: Patients receive pegfilgrastim subcutaneously (SC) followed by rituximab intravenously (IV) 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 2 years, and then yearly for 1 year.

Official Title
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Phase II Clinical Trial of Rituximab in Combination With Pegfilgrastim in Patients With Indolent B-Cell (CD-20-Positive) Lymphoma

Conditions
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Contiguous Stage II Grade 1 Follicular Lymphoma, Contiguous Stage II Grade 2 Follicular Lymphoma, Contiguous Stage II Grade 3 Follicular Lymphoma, Contiguous Stage II Marginal Zone Lymphoma, Contiguous Stage II Small Lymphocytic 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 Grade 3 Follicular Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Small Lymphocytic Lymphoma, Splenic Marginal Zone Lymphoma, Stage I Grade 1 Follicular Lymphoma, Stage I Grade 2 Follicular Lymphoma, Stage I Grade 3 Follicular Lymphoma, Stage I Marginal Zone Lymphoma, Stage I Small Lymphocytic Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Small Lymphocytic Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Small Lymphocytic Lymphoma

Intervention / Treatment
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* Biological: pegfilgrastim
* Biological: rituximab
* Other: flow cytometry
* Procedure: biopsy
* Other: immunohistochemistry staining method
* Genetic: western blotting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated or relapsed/refractory follicular, SLL or MZL (i.e. no limit to number of prior treatments as long as patients meet other study criteria) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Measurable tumor size (at least one node measuring 4 cm^2 in bidimensional measurement) Expected survival of > 6 months Prior rituximab or other monoclonal immunotherapy permitted and eligible for rituximab monotherapy Full recovery from any significant toxicity associated with prior surgery, radiation therapy, chemotherapy, or immunotherapy Absolute neutrophil count > 1.0 x 10^9/L Platelets > 50 x 10^9/L Patients may receive erythropoietin growth factors to maintain adequate hemoglobin levels (>= 8.0 mg/dl) Creatinine < 1.5 x upper normal levels (UNL) Total bilirubin < 1.5 mg/dL (> 25.65 umol/L) Aspartate aminotransferase < 5 x UNL Alkaline phosphatase < 5 x UNL Informed consent approved in institutional review board (lRB) CD20+ B-cell lymphoma Exclusion Criteria: Prior history of human immunodeficiency virus (HIV)-positivity (routine HIV testing is required pretreatment) Serious non-malignant disease (e.g. active uncontrolled bacterial, viral, or fungal infections) or other conditions which, in the opinion of the principal investigator would compromise other protocol objectives Presence of central nervous system (CNS) lymphoma Chemotherapy within 4 weeks of the first scheduled study treatment Another primary malignancy (other than squamous or basal cell carcinoma of the skin or in-situ carcinoma of the cervix) for which the patient has not been disease-free for at least five years Major surgery, other than diagnostic surgery, within four weeks Patients with non-Hodgkin lymphoma (NHL) other than relapsed/refractory follicular, MZL or SLL Patients must not have a history of cardiac disease, defined as New York Heart Association Class II or greater or clinical evidence of congestive heart failure Concurrent use of other investigational agents Pregnant or breast feeding Subjects of reproductive potential who are not using adequate contraceptive precautions, in the judgment of the investigator Known hypersensitivity to any recombinant E coli-derived product, murine proteins, or any components of the study medications Concerns for the subject's compliance with the protocol Any premalignant myeloid condition or any malignancy with myeloid characteristics (e.g. myelodysplastic syndromes, acute or chronic myelogenous leukemia) Patient is currently enrolled in, or has not yet completed at least 30 days since ending another investigational device or drug trial

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (colony-stimulating factor and monoclonal antibody)<br>Patients receive pegfilgrastim SC followed by rituximab IV 3 days later in weeks 1, 3, 5, 7, 15, 23, 31, and 39. Treatment continues in the absence of disease progression or unacceptable toxicity. | Biological: pegfilgrastim<br>* Given SC<br>* Other names: SD-01 sustained duration G-CSF;Biological: rituximab<br>* Given IV<br>* Other names: Rituxan;Other: flow cytometry<br>* Correlative studies<br>Procedure: biopsy<br>* Correlative studies<br>* Other names: biopsies;Other: immunohistochemistry staining method<br>* Correlative studies<br>* Other names: immunohistochemistry;Genetic: western blotting<br>* Correlative studies<br>* Other names: Western Blot;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Grade 1: Mild AE; Grade 2: Moderate AE; Grade 3: Severe AE; Grade 4: Life-threatening or disabling AE; Grade 5: Death related to AE | Up to 90 days after the last dose of study drugs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall Response is defined as Complete Response: During observation, no disease is apparent, including measurable and non-measurable disease, and no evidence of disease is observed for at least 28 days, as confirmed by a second assessment following the original observation of no disease; and Partial Response: A 50% or greater decrease from baseline in the sum of the products of the longest perpendicular diameters of all the measured lesions is noted for at least 28 days as confirmed by a second assessment following the observation of the 50% or greater decrease, and no appearance of new lesions is noted. | Up to 43 weeks | 
| Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | Mean percent change in CD11b level from baseline at each visit | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 | 
| Percent Change in CD20 Antigen Expression and Density of Expression | Percent change in CD20 antigen expression and density of expression | At 4 years | 
| Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | Mean percent change in TNF level from baseline at each visit. | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 | 
| Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | Mean percent change in INF level from baseline. | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 | 
| Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | Mean percent change in MFI level from baseline. | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 |