Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma

Phase 2

Completed

• Conditions: Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Stage I Marginal Zone Lymphoma
• Interventions: Biological: pegfilgrastim; Biological: rituximab; Other: flow cytometry; Procedure: biopsy; Other: immunohistochemistry staining method; Genetic: western blotting

• Registration Number: NCT01682044
• Lead Sponsor: Roswell Park Cancer Institute

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.

Study Timeline

• Study Start: 2007-04-17
• Study First Submitted: 2012-09-05
• Study First Submitted QC: 2012-09-07
• Study First Posted: 2012-09-10
• Primary Completion: 2013-11-22
• Study Completion: 2016-12-22
• Results First Submitted: 2017-06-14
• Status Verified: 2017-09
• Results First Submitted QC: 2017-09-08
• Last Update Submitted: 2017-09-08
• Results First Posted: 2017-10-09
• Last Update Posted: 2017-10-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (colony-stimulating factor and monoclonal antibody)	flow cytometry	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.
Treatment (colony-stimulating factor and monoclonal antibody)	rituximab	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.
Treatment (colony-stimulating factor and monoclonal antibody)	western blotting	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.
Treatment (colony-stimulating factor and monoclonal antibody)	pegfilgrastim	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.
Treatment (colony-stimulating factor and monoclonal antibody)	immunohistochemistry staining method	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.
Treatment (colony-stimulating factor and monoclonal antibody)	biopsy	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 CD20 Antigen Expression and Density of Expression	At 4 years	Percent change in CD20 antigen expression and density of expression
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.
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 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 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.

Trial Locations

Locations (1)

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States