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 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 I Marginal Zone Lymphoma, Stage I 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
Conditions
Brief summary
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
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.
Interventions
Correlative studies
Correlative studies
Correlative studies
Given SC
Given IV
Correlative studies
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Up to 90 days after the last dose of study drugs | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 | Mean percent change in CD11b level from baseline at each visit |
| Percent Change in CD20 Antigen Expression and Density of Expression | At 4 years | Percent change in CD20 antigen expression and density of expression |
| Overall Response Rate | Up to 43 weeks | 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. |
| Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 | Mean percent change in INF level from baseline. |
| Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 | Mean percent change in MFI level from baseline. |
| Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 | Mean percent change in TNF level from baseline at each visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) 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.
pegfilgrastim: Given SC
rituximab: Given IV
flow cytometry: Correlative studies
biopsy: Correlative studies
immunohistochemistry staining method: Correlative studies
western blotting: Correlative studies | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Progression | 3 |
Baseline characteristics
| Characteristic | Treatment (Colony-stimulating Factor and Monoclonal Antibody) |
|---|---|
| Age, Continuous | 60.9 years STANDARD_DEVIATION 13.1 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 2 / 20 |
Outcome results
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
Time frame: Up to 90 days after the last dose of study drugs
Population: All treated and eligible patients
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Number of Participants With Adverse Events | Grade 1 | 3 Participants |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Number of Participants With Adverse Events | Grade 2 | 9 Participants |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Number of Participants With Adverse Events | Grade 3 | 6 Participants |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Number of Participants With Adverse Events | Grade 4 | 1 Participants |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Number of Participants With Adverse Events | Grade 5 | 1 Participants |
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.
Time frame: Up to 43 weeks
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Overall Response Rate | 60 percentage of participants |
Percent Change in CD20 Antigen Expression and Density of Expression
Percent change in CD20 antigen expression and density of expression
Time frame: At 4 years
Population: Samples tissues were not large enough to perform analysis. No participants were analyze.
Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline
Mean percent change in CD11b level from baseline at each visit
Time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 1 | -20.2 percent change | Standard Deviation 34 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 3 | -35.5 percent change | Standard Deviation 28.3 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 5 | -24.7 percent change | Standard Deviation 117.7 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 7 | -56.8 percent change | Standard Deviation 27.4 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 15 | -23.8 percent change | Standard Deviation 40.1 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 23 | -19.7 percent change | Standard Deviation 35.7 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 31 | -18.7 percent change | Standard Deviation 47 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Functional and Phenotypic Characteristics of Host Neutrophils From Baseline | week 39 | -10.1 percent change | Standard Deviation 42.7 |
Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline
Mean percent change in MFI level from baseline.
Time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 1 | -32.0 percent change | Standard Deviation 66.8 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 3 | -22.4 percent change | Standard Deviation 71 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 5 | -45.4 percent change | Standard Deviation 66.5 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 7 | -20.4 percent change | Standard Deviation 89.9 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 15 | -5.8 percent change | Standard Deviation 137.6 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 23 | 0.4 percent change | Standard Deviation 219.1 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 31 | 295.8 percent change | Standard Deviation 996.1 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Free Radical Levels (MFI) From Baseline | week 39 | 16.0 percent change | Standard Deviation 285.6 |
Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline
Mean percent change in INF level from baseline.
Time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 1 | -18.8 percent change | Standard Deviation 33.2 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 3 | -27.8 percent change | Standard Deviation 42.9 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 5 | 48.1 percent change | Standard Deviation 124.6 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 7 | 8.0 percent change | Standard Deviation 71.4 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 15 | 1.5 percent change | Standard Deviation 78.6 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 23 | -14.1 percent change | Standard Deviation 43.9 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 31 | -33.0 percent change | Standard Deviation 49.5 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Interferon Alpha (INF) From Baseline | week 39 | -7.5 percent change | Standard Deviation 45.1 |
Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline
Mean percent change in TNF level from baseline at each visit.
Time frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 1 | 51.5 percent change | Standard Deviation 65.1 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 3 | 14.5 percent change | Standard Deviation 47.7 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 5 | 11.2 percent change | Standard Deviation 50.1 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 7 | 8.3 percent change | Standard Deviation 34.2 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 15 | 42.7 percent change | Standard Deviation 76.4 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 23 | 27.2 percent change | Standard Deviation 80.6 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 31 | 45.6 percent change | Standard Deviation 100.5 |
| Treatment (Colony-stimulating Factor and Monoclonal Antibody) | Percent Change in Serum Levels of Tumor Necrosis Factor (TNF) From Baseline | week 39 | 50.2 percent change | Standard Deviation 110.6 |