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 sargramostim increase the number of immune cells found in bone marrow and peripheral blood. It is not yet known whether combining rituximab and sargramostim with vaccine therapy may cause a stronger immune response and kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of combining rituximab and sargramostim with or without vaccine therapy in treating patients who have newly diagnosed, relapsed, or refractory B-cell non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
grade 1 follicular lymphoma grade 2 follicular lymphoma grade 3 follicular lymphoma	Drug: autologous immunoglobulin idiotype-KLH conjugate vaccine  Drug: rituximab  Drug: sargramostim  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: monoclonal antibody therapy  Procedure: tumor cell derivative vaccine  Procedure: vaccine therapy	Phase III

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. Six 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 thereafter.

PROJECTED ACCRUAL: A total of 342 (171 per treatment arm) patients will be accrued for this study within 18 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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 autoimmune disease
• No prior allergic response to sargramostim (GM-CSF)
• No active bacterial, viral, or fungal infection

Other

• Not pregnant or nursing
• 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

• Not specified

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

California
      Comprehensive Blood and Cancer Center, Bakersfield,  California,  93309-0633,  United States; Recruiting
      Hoag Memorial Hospital Presbyterian, Newport Beach,  California,  92658,  United States; Recruiting
      Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego, San Diego,  California,  92120,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0960,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5151,  United States; Recruiting
      Tower Hematology Oncology Medical Group, Beverly Hills,  California,  90211,  United States; Recruiting
Delaware
      Medical Oncology Hematology Consultants, P.A. at Helen F. Graham Cancer Center, Newark,  Delaware,  19713-2055,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
Florida
      Center for Hematology-Oncology, Boca Raton,  Florida,  33486,  United States; Recruiting
      University of Florida Health Science Center - Jacksonville, Jacksonville,  Florida,  32209,  United States; Recruiting
Idaho
      North Idaho Cancer Center, Coeur D Alene,  Idaho,  83814,  United States; Recruiting
Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States; Recruiting
Kansas
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0093,  United States; Recruiting
Louisiana
      Ochsner Clinic Foundation, New Orleans,  Louisiana,  70121,  United States; Recruiting
Maryland
      Cancer Center at Greater Baltimore Medical Center, Baltimore,  Maryland,  21204-6881,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Michigan
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202-2608,  United States; Recruiting
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Montana
      Montana Cancer Specialists, Missoula,  Montana,  59802,  United States; Recruiting
New Mexico
      New Mexico Cancer Center, Albuquerque,  New Mexico,  87109,  United States; Recruiting
New York
      Comprehensive Cancer Center at Our Lady of Mercy Medical Center, Bronx,  New York,  10466-2604,  United States; Recruiting
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
North Dakota
      Mid Dakota Clinic, P.C., Bismarck,  North Dakota,  58502-5538,  United States; Recruiting
Ohio
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45219,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
      Ireland Cancer Center, Cleveland,  Ohio,  44106,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States; Recruiting
      Providence Cancer Center at Providence Portland Medical Center, Portland,  Oregon,  97213,  United States; Recruiting
Pennsylvania
      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States; Recruiting
      Geisinger Medical Center, Danville,  Pennsylvania,  17822-2001,  United States; Recruiting
      Western Pennsylvania Cancer Institute, Pittsburgh,  Pennsylvania,  15224-1791,  United States; Recruiting
Tennessee
      Sarah Cannon Cancer Center at Centennial Medical Center, Nashville,  Tennessee,  37203,  United States; Recruiting
Texas
      Cancer Care Network of South Texas, San Antonio,  Texas,  78229,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting
Washington
      North Star Lodge Cancer Center, Yakima,  Washington,  98902,  United States; Recruiting
      Swedish Cancer Institute at Swedish Medical Center - First Hill Campus, Seattle,  Washington,  98104,  United States; Recruiting
Wisconsin
      Marshfield Clinic, Marshfield,  Wisconsin,  54449,  United States; Recruiting

Study chairs or principal investigators

John C. Gutheil, MD,  Study Chair,  Favrille   

Study ID Numbers:  CDR0000378046; FAV-ID-06; FAV-WIRB-20040335
Record last reviewed:  October 2004
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089115
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-10