GM-CSF and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. 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. Giving GM-CSF together with rituximab may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving GM-CSF together with rituximab works in treating patients with previously untreated follicular non-Hodgkin lymphoma.

Detailed Description
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OBJECTIVES: Primary Evaluate the clinical efficacy of sargramostim (GM-CSF) and rituximab, in terms of overall objective complete and partial response rates, in patients with previously untreated follicular non-Hodgkin lymphoma. Secondary Evaluate the time to progression in patients treated with this regimen. Evaluate the overall survival of patients treated with this regimen. Evaluate the duration of response in patients treated with this regimen. Evaluate the safety profile of this regimen in these patients. Evaluate the influence of FcγR polymorphisms on clinical response. Monitor FcγR-expressing cells in peripheral blood during treatment. Monitor the molecular biological marker bcl2 [t(14;18)] in peripheral blood and bone marrow. OUTLINE: This is a multicenter study. Induction therapy: Patients receive sargramostim (GM-CSF) subcutaneously (SC) on days 1-5 and rituximab IV on day 1. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Maintenance therapy: Patients receive GM-CSF SC on days 1-5 and rituximab IV on day 1. Treatment repeats every 8 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Blood and bone marrow samples are collected at baseline and periodically during study for analysis of bcl2 rearrangement by PCR assay; FcγR expression by immunophenotyping; and FcγR polymorphisms. After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for up to 4 years.

Official Title
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An Open Label, Multicenter, Non Randomized Phase II Study to Evaluate Anti-tumor Efficacy and Safety of GM-CSF (Sargramostim, Leukine®) Associated With Rituximab (MabThera®) in Patients With Follicular Non Hodgkin's Lymphoma With no Prior Treatment

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Biological: sargramostim
* Genetic: gene expression analysis
* Genetic: gene rearrangement analysis
* Genetic: polymerase chain reaction
* Genetic: polymorphism analysis
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically and immunophenotypically confirmed CD20+ follicular lymphoma according to WHO classification Grade 1-3a disease Stage II-IV disease Non-bulky disease Must have undergone initial nodal biopsy within the past 4 months At least 1 measurable lesion Low tumor-burden, as defined by the following GELF criteria: Nodal or extranodal tumor mass (diameter < 7 cm) No systemic B symptoms No increased LDH and β2 microglobulinemia No substantial splenic enlargement No serous effusion No compression syndrome PATIENT CHARACTERISTICS: ECOG performance status 0-1 Negative pregnancy test Fertile patients must use effective contraception No active hepatitis PRIOR CONCURRENT THERAPY: No prior treatment, including steroids and radiotherapy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: rituximab|nan|
|Biological: sargramostim|nan|
|Genetic: gene expression analysis|nan|
|Genetic: gene rearrangement analysis|nan|
|Genetic: polymerase chain reaction|nan|
|Genetic: polymorphism analysis|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall objective tumor response rate at the end of induction therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression |  |  | 
| Overall survival |  |  | 
| Duration of response |  |  | 
| Time to next treatment |  |  | 
| Safety profile |  |  | 
| Influence of FcγR polymorphisms on clinical response and survival |  |  | 
| FcγR expression during study treatment |  |  | 
| Molecular biological marker bcl2 [t(14;18)] in peripheral blood and bone marrow as measured by PCR assay |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II grade 1 follicular lymphoma, stage II grade 2 follicular lymphoma, stage II grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma