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.

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: non-specific immune-modulator therapy  Procedure: tumor cell derivative vaccine  Procedure: vaccine therapy	Phase III

Further Study Details: 

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 (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 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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States; Recruiting
California
      Cancer Institute Medical Group - Santa Monica, Santa Monica,  California,  90404,  United States; Recruiting
      Comprehensive Blood and Cancer Center, Bakersfield,  California,  93309-0633,  United States; Recruiting
      Hoag Cancer Center at Hoag Memorial Hospital Presbyterian, Newport Beach,  California,  92663,  United States; Recruiting
      Kaiser Permanente Medical Center - Vallejo, Vallejo,  California,  94589,  United States; Recruiting
      Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego, San Diego,  California,  92120,  United States; Recruiting
      North Valley Hematology-Oncology Medical Group, Northridge,  California,  91328,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0960,  United States; Recruiting
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      Sharp Memorial Hospital, San Diego,  California,  92123,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5151,  United States; Recruiting
      Tower Cancer Research Foundation, Beverly Hills,  California,  90211,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94143-0324,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90089,  United States; Recruiting
      Wilshire Oncology Medical Group, Incorporated - La Verne, La Verne,  California,  91750,  United States; Recruiting
Colorado
      Rocky Mountain Cancer Centers - Denver Midtown, Denver,  Colorado,  80218,  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
      H. Lee Moffitt Cancer Center and Research Institute at University of South Florida, Tampa,  Florida,  33612-9497,  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
Illinois
      Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
      Rush University Medical Center, Chicago,  Illinois,  60612,  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 Cancer Institute at 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
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202-2608,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Montana
      Montana Cancer Specialists at Montana Cancer Center, Missoula,  Montana,  59802,  United States; Recruiting
New Mexico
      New Mexico Cancer Center, Albuquerque,  New Mexico,  87109,  United States; Recruiting
New York
      Beth Israel Medical Center - Philipps Ambulatory Care Center, New York,  New York,  10003,  United States; Recruiting
      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 Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      St. Vincent's Comprehensive Cancer Center - Manhattan, New York,  New York,  10011,  United States; Recruiting
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
North Dakota
      Meritcare Roger Maris Cancer Center, Fargo,  North Dakota,  58122,  United States; Recruiting
      Mid Dakota Clinic, P.C., Bismarck,  North Dakota,  58502-5538,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
      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 at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-7284,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States; Recruiting
      Kaiser Permanente Medical Office - Interstate Medical Office Central, Portland,  Oregon,  97227,  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
      Frank M. & Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center, Wilkes Barre,  Pennsylvania,  18711,  United States; Recruiting
      Geisinger Medical Center, Danville,  Pennsylvania,  17822-0001,  United States; Recruiting
      Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States; Recruiting
Tennessee
      Sarah Cannon Cancer Center at Centennial Medical Center, Nashville,  Tennessee,  37203,  United States; Recruiting
Texas
      Baylor University Medical Center, Dallas,  Texas,  75246,  United States; Recruiting
      Cancer Care Network of South Texas, San Antonio,  Texas,  78229,  United States; Recruiting
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting
Virginia
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  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
      Washington Hematology - Oncology Specialists, Yakima,  Washington,  98902,  United States; Recruiting
Wisconsin
      Marshfield Clinic - Marshfield Center, Marshfield,  Wisconsin,  54449,  United States; Recruiting
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-5256,  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; NCT00089115; CWRU-FVID-1404
Record last reviewed:  March 2005
Last Updated:  April 4, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089115
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08