GM-CSF, Rituximab, and Combination Chemotherapy in Treating Patients With Previously Untreated Advanced Follicular Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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RATIONALE: 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Colony-stimulating factors, such as GM-CSF, may cause the body to make more blood cells and help it recover from the side effects of rituximab and combination chemotherapy. PURPOSE: This phase II trial is studying how well giving GM-CSF together with rituximab and combination chemotherapy works in treating patients with previously untreated advanced follicular non-Hodgkin lymphoma.

Detailed Description
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OBJECTIVES: Primary To evaluate the overall objective tumor response rate (complete and partial response rates) in patients with previously untreated advanced follicular non-Hodgkin lymphoma treated with sargramostim (GM-CSF) and R-CHOP. Secondary To evaluate the time to progression. To evaluate the overall survival. To evaluate the duration of response. To evaluate the time to next treatment. To evaluate the safety profile of GM-CSF in combination with R-CHOP. To evaluate the influence of FcγR polymorphisms on clinical response. To monitor FcγR expressing cells in peripheral blood during treatment. To monitor the molecular biological marker bcl-2 [t(14;18)] in peripheral blood and bone marrow by quantitative PCR assay. OUTLINE: This is a multicenter study. Induction therapy: Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and oral prednisone on days 1-5. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) on days 2-6. Treatment repeats every 21 days for up to 6 courses. Patients then receive rituximab IV on day 1 and GM-CSF SC on days 1-5. Treatment with rituximab and GM-CSF repeats every 21 days for 2 courses. Patients achieving complete or partial response proceed to maintenance therapy. Maintenance therapy: Patients receive rituximab IV on day 1 and GM-CSF SC on days 1-5. Treatment repeats every 2 months for 12 courses. Blood and bone marrow samples are collected at baseline and periodically during study for analysis of FcγR expression by immunophenotyping and bcl-2 rearrangement by quantitative PCR. After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Official Title
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An Open Label, Multicenter, Non Randomized Phase II Study to Evaluate Antitumor Efficacy and Safety of GM-CSF (Sargramostim, Leukine®) Associated With RCHOP Chemotherapy and Rituximab (MabThera®) Maintenance in Patients With First-line Advanced Follicular Non Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Biological: sargramostim
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate
* Genetic: gene expression analysis
* Genetic: gene rearrangement analysis
* Genetic: polymerase chain reaction
* Other: R-CHOP regimen
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed follicular non-Hodgkin lymphoma Grade 1-3a disease Advanced disease Has undergone initial lymph node biopsy within the past 4 months At least 1 measurable lesion Bulky disease, as defined by the following GELF criteria: Nodal or extranodal mass > 7 cm in its greatest diameter Involvement of ≥ 3 nodal sites (each with a diameter > 3 cm) B symptoms Elevated serum LDH or β2-microglobulin Splenic enlargement Compression syndrome Pleural and/or peritoneal effusion No transformation to high-grade follicular lymphoma (secondary to low-grade follicular lymphoma) No prior or concurrent CNS disease (i.e., CNS lymphoma or lymphomatous meningitis) NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 6 months ANC ≥ 1,000/mm^3* Platelet count ≥ 100,000/mm^3* Hemoglobin ≥ 8.0 g/dL* Total bilirubin ≤ 2.0 mg/dL* AST ≤ 3 times upper limit of normal* Serum creatinine ≤ 2.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 months after completion of study treatment No known HIV infection No active hepatitis B or C infection No serious underlying medical condition that would preclude study participation (e.g., ongoing infection, uncontrolled diabetes mellitus, gastric ulcer, active autoimmune disease, or heart failure) No known sensitivity or allergy to murine products No other prior or concurrent malignancies except nonmelanoma skin cancer or adequately treated in situ cervical cancer No other co-existing medical or psychological condition that would preclude study participation or ability to give informed consent NOTE: *Unless abnormalities are related to lymphoma PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior treatment for follicular lymphoma, including steroids or radiotherapy More than 4 weeks since prior corticosteroids unless administered at a dose equivalent to < 20 mg/day of prednisone More than 28 days since prior major surgery (excluding lymph node biopsy) More than 30 days since prior treatment in a clinical trial

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|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: prednisone|nan|
|Drug: vincristine sulfate|nan|
|Genetic: gene expression analysis|nan|
|Genetic: gene rearrangement analysis|nan|
|Genetic: polymerase chain reaction|nan|
|Other: R-CHOP regimen|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 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to treatment progression |  |  | 
| Overall survival |  |  | 
| Duration of response |  |  | 
| Time to next treatment |  |  | 
| Safety profile |  |  | 
| Influence of FcγR polymorphisms on clinical response and overall survival |  |  | 
| Monitoring of FcγR expressing cells during treatment |  |  | 
| Quantitative monitoring of the molecular biological marker bcl-2 in peripheral blood and bone marrow by PCR assay |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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