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

• ClinicalTrials.gov Identifier: NCT01682044
• Recruitment Status: Completed
• First Posted: September 10, 2012
• Results First Posted: October 9, 2017
• Last Update Posted: October 9, 2017
• Sponsor: Roswell Park Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Roswell Park Cancer Institute

Tracking Information

• First Submitted Date: September 5, 2012
• First Posted Date: September 10, 2012
• Results First Submitted Date: June 14, 2017
• Results First Posted Date: October 9, 2017
• Last Update Posted Date: October 9, 2017
• Study Start Date: April 17, 2007
• Actual Primary Completion Date: November 22, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 8, 2017)

Number of Participants With Adverse Events [ Time Frame: 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

Original Primary Outcome Measures (submitted: September 7, 2012)

• Overall response rate (ORR) [ Time Frame: Up to 43 weeks ]
  Two-sided 95% exact confidence intervals around the estimates will be calculated. Overall performance on study (weight loss, change in Karnofsky Scores) will be measured. Radiologic evaluation of the extent of disease following therapy will be used to assess response according to the standard World Health Organization (WHO) response criteria.
• Complete response (CR) [ Time Frame: Up to 43 weeks ]
  Two-sided 95% exact confidence intervals around the estimates will be calculated. Summarized overall for the intent-to-treat and the evaluable populations. Overall performance on study (weight loss, change in Karnofsky Scores) will be measured. Radiologic evaluation of the extent of disease following therapy will be used to assess response according to the standard WHO response criteria.
• Partial response (PR) rates [ Time Frame: Up to 43 weeks ]
  Two-sided 95% exact confidence intervals around the estimates will be calculated. Summarized overall for the intent-to-treat and the evaluable populations. Overall performance on study (weight loss, change in Karnofsky Scores) will be measured. Radiologic evaluation of the extent of disease following therapy will be used to assess response according to the standard WHO response criteria.

Current Secondary Outcome Measures (submitted: September 8, 2017)

• Overall Response Rate [ Time Frame: 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 Functional and Phenotypic Characteristics of Host Neutrophils From Baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline and weeks 1, 3, 5, 7, 15, 23, 31, and 39 ]
  Mean percent change in MFI level from baseline.

Original Secondary Outcome Measures (submitted: September 7, 2012)

• Time to disease progression, defined as date of progression/death/last contact to the date treatment started [ Time Frame: At 2 years ]
  Descriptive statistics such as median, minimum, and maximum values will be used to summarize the time to event data. Kaplan-Meier estimates will be used.
• Time to disease progression, defined as date of progression/death/last contact to the date treatment started [ Time Frame: At 4 years ]
  Descriptive statistics such as median, minimum, and maximum values will be used to summarize the time to event data. Kaplan-Meier estimates will be used.
• Survival, defined as date of death/last contact to the date treatment started [ Time Frame: At 2 years ]
  Descriptive statistics such as median, minimum, and maximum values will be used to summarize the time to event data. Kaplan-Meier estimates will be used. Overall performance on study (weight loss, change in Karnofsky Scores) will be measured.
• Survival, defined as date of death/last contact to the date treatment started [ Time Frame: At 4 years ]
  Descriptive statistics such as median, minimum, and maximum values will be used to summarize the time to event data. Kaplan-Meier estimates will be used. Overall performance on study (weight loss, change in Karnofsky Scores) will be measured.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pegfilgrastim and Rituximab in Treating Patients With Untreated, Relapsed, or Refractory Follicular Lymphoma, Small Lymphocytic Lymphoma, or Marginal Zone Lymphoma
• Official Title: Phase II Clinical Trial of Rituximab in Combination With Pegfilgrastim in Patients With Indolent B-Cell (CD-20-Positive) Lymphoma
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

• Biological: pegfilgrastim
  Given SC
  Other Names:

  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF
• Biological: rituximab
  Given IV
  Other Names:

  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
• Other: flow cytometry
  Correlative studies
• Procedure: biopsy
  Correlative studies
  Other Name: biopsies
• Other: immunohistochemistry staining method
  Correlative studies
  Other Name: immunohistochemistry
• Genetic: western blotting
  Correlative studies
  Other Names:

  • Blotting, Western
  • Western Blot

Study Arms

Experimental: 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.

Interventions:

• Biological: pegfilgrastim
• Biological: rituximab
• Other: flow cytometry
• Procedure: biopsy
• Other: immunohistochemistry staining method
• Genetic: western blotting

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 17, 2013): 20
• Original Estimated Enrollment (submitted: September 7, 2012): 40
• Actual Study Completion Date: December 22, 2016
• Actual Primary Completion Date: November 22, 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01682044
• Other Study ID Numbers: I 83106; NCI-2011-00134 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Roswell Park Cancer Institute
• Study Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Francisco Hernandez-ILizaliturri; Roswell Park Cancer Institute

• PRS Account: Roswell Park Cancer Institute
• Verification Date: September 2017