Vaccine Therapy and Sargramostim Compared With Placebo and Sargramostim Following Rituximab in Treating Patients With Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Vaccines made from a person's cancer cells may make the body build an immune response to kill cancer cells. Colony-stimulating factors such as GM-CSF increase the number of immune cells found in bone marrow and peripheral blood. It is not yet known whether combining rituximab and GM-CSF with vaccine therapy may cause a stronger immune response and kill more cancer cells. PURPOSE: This randomized phase III trial is studying giving rituximab and GM-CSF together with vaccine therapy and comparing it to giving rituximab and GM-CSF alone in treating patients with newly diagnosed, relapsed, or refractory B-cell non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Compare time to disease progression in patients with grade 1, 2, or 3 follicular B-cell non-Hodgkin's lymphoma who respond (i.e., complete or partial response, or stable disease) to treatment with rituximab and are then treated with sargramostim (GM-CSF) with vs without autologous immunoglobulin idiotype-KLH conjugate vaccine. Secondary Compare response rate improvement in patients treated with these regimens. Compare overall complete response rate in patients treated with these regimens. Compare duration of response in patients treated with these regimens. Determine the safety of these regimens in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior treatment (yes vs no) and response to rituximab during study (complete response [CR] or partial response [PR] vs stable disease [SD]). All patients receive rituximab IV once weekly for 4 weeks. Five weeks after the last dose of rituximab, patients are assessed for response. Patients with progressive disease are removed from the study and do not undergo randomization. Patients with a CR, PR, or SD are randomized to 1 of 2 treatment arms. Arm I: Patients receive autologous immunoglobulin idiotype-KLH conjugate vaccine subcutaneously (SC) on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4. Arm II: Patients receive placebo SC on day 1. Patients also receive GM-CSF SC on days 1-4. In both arms, treatment repeats monthly for 6 months in the absence of unacceptable toxicity or clinically significant progressive disease. After the first 6 months, patients with a CR, PR, or SD may continue to receive treatment (per treatment arm as above) every 2 months for 1 year (total of 6 doses) and then every 3 months thereafter in the absence of disease progression. Patients are followed every 3 months for 2 years and then every 6 months until disease progression. PROJECTED ACCRUAL: A total of 342 evaluable patients (171 per treatment arm) will be accrued for this study within 18 months.

Official Title
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Phase III, Randomized, Double Blind, Placebo-Controlled Trial of Favldand GM-CSF Versus Placebo and GM-CSF Following Rituximab in Subjects With Follicular B-Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine
* Biological: rituximab
* Biological: sargramostim


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL) Grade 1, 2, or 3 Meets 1 of the following criteria for treatment with rituximab: Treatment naïve Relapsed or refractory disease after prior chemotherapy Relapsed after a prior documented response (i.e., complete or partial response) to rituximab of at least 6 months duration Tumor accessible for biopsy OR existing biopsy material (taken within the past 6 months) suitable for vaccine preparation Measurable or evaluable disease after tumor tissue procurement for vaccine production No more than 2 prior treatment regimens for NHL Single regimens include any of the following: Maintenance rituximab Rituximab administered once weekly for 8 courses Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab* NOTE: *CHOP followed by rituximab at time of relapse is considered 2 treatment regimens No history of CNS lymphoma or meningeal lymphomatosis PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm^3 (unless related to bone marrow involvement by lymphoma) Hemoglobin ≥ 10g/dL Hepatic Not specified Renal Not specified Cardiovascular No congestive heart failure Pulmonary No compromised pulmonary function Immunologic HIV negative No prior allergic response to GM-CSF No active bacterial, viral, or fungal infection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No psychiatric disorder that would preclude study participation No other malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No other serious nonmalignant disease that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics See Chemotherapy At least 4 weeks since prior immunotherapy No prior radiolabeled anti-lymphoma antibody (e.g., iodine I 131 tositumomab or ibritumomab tiuxetan) No prior autologous or allogeneic stem cell transplantation No prior lymphoma-specific idiotype immunotherapy (e.g., Id vaccine) No prior investigational vaccine or immunotherapeutic containing keyhole limpet hemocyanin (KLH) Chemotherapy See Disease Characteristics At least 4 weeks since prior chemotherapy More than 9 months since prior fludarabine More than 2 years since prior chemotherapy/rituximab combination therapy (e.g., CHOP/rituximab or cyclophosphamide, vincristine, and prednisone [CVP]/rituximab) No more than 6 total prior treatment courses with fludarabine Endocrine therapy No concurrent steroids for allergic reaction to sargramostim (GM-CSF) Radiotherapy See Biologic therapy At least 4 weeks since prior radiotherapy Surgery Not specified Other At least 4 weeks since prior experimental therapy No concurrent systemic immunosuppressive therapy No other concurrent anti-lymphoma therapy

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: Randomized
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: autologous immunoglobulin idiotype-KLH conjugate vaccine|nan|
|Biological: rituximab|nan|
|Biological: sargramostim|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression after 248 patients have progressed |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate improvement after 248 patients have progressed |  |  | 
| Overall complete response rate by modified Cheson Criteria after 248 patients have progressed |  |  | 
| Duration of response by modified Cheson Criteria after 248 patients have progressed |  |  | 
| Safety by Common Toxicity Criteria (CTC) after 248 patients have progressed |  |  | 

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