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. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug with rituximab may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of rituximab plus combination chemotherapy in treating patients who have intermediate-grade or high-grade non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
Lymphoma	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: monoclonal antibody therapy  Procedure: colony-stimulating factor therapy  Procedure: antibody therapy  Procedure: cytokine therapy  Drug: cyclophosphamide  Drug: doxorubicin  Drug: filgrastim  Drug: prednisone  Drug: rituximab  Drug: vincristine	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the rate of complete response and partial response in patients with intermediate or high grade non-Hodgkin's lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). II. Determine the toxicity of this regimen in these patients. III. Determine the disease-free and overall survival, time to response, and time to disease progression in patients treated with this regimen.

PROTOCOL OUTLINE: This is a multicenter study. Patients are stratified according to the number of risk factors (0-2 vs 3-5). Risk factors include age (no greater than 60 vs greater than 60), tumor stage (II vs III or IV), number of extranodal sites (no more than 1 vs more than 1), performance status (0-1 vs 2-4), and serum LDH level (no greater than normal vs greater than normal). Patients receive rituximab IV on day 1; cyclophosphamide, doxorubicin, and vincristine IV on day 3; and oral prednisone on days 3-7. Patients over 60 also receive filgrastim (G-CSF) subcutaneously beginning on day 4 and continuing until blood counts recover (all other patients receive G-CSF as secondary prophylaxis). Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who respond receive 2 more courses. Patients who have no measurable disease after 6 courses receive rituximab IV once weekly for 4 consecutive weeks. This treatment continues every 6 months for 4 courses in the absence of disease progression or unacceptable toxicity. Patients who have measurable disease after 6 courses of chemotherapy receive 2 more courses for a maximum of 8 courses of CHOP, followed by maintenance therapy with rituximab (as described above). Patients are followed every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed intermediate or high grade non-Hodgkin's lymphoma; Stage II, III, or IV disease; B-cell where lymphoid cells are CD20 or CD19 positive
• No mantle cell, lymphoblastic, or peripheral T-cell non-Hodgkin's lymphoma
• Measurable or evaluable disease
• No prior treatment for lymphoma
• No known CNS metastases

[A new classification scheme for adult non-Hodgkin's 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.]

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics; No concurrent biologic therapy except epoetin alfa; No white blood cell transfusions
• Chemotherapy: See Disease Characteristics; No concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; No concurrent radiotherapy
• Surgery: At least 2 weeks since prior major surgery
• Other: No other concurrent investigational therapy; No prophylactic antibiotics

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 60-100%
• Life expectancy: At least 12 weeks
• Hematopoietic: Unless documented bone marrow disease: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: SGOT and SGPT no greater than 3 times upper limit of normal; Bilirubin no greater than 1.5 mg/dL
• Renal: Creatinine no greater than 2.0 mg/dL
• Cardiovascular: No history of severe heart disease, cardiomyopathy, or congestive heart failure; LVEF normal by MUGA or echocardiogram
• Other: Not pregnant or nursing; Fertile patients must use effective contraception; No active infection as defined by: Clinical syndrome consistent with a viral or bacterial infection (e.g., influenza, upper respiratory infection, urinary tract infection) OR Fever with a clinical site of infection identified OR Microbiologically documented infection, including, but not limited to, bacteremia or septicemia; No known HIV positivity; No known sensitivity to E. coli derivatives (e.g., asparaginase, human insulin, human growth hormone, interferon alfa-2b); No other prior malignancy within the past 5 years except surgically cured basal or squamous cell skin cancer or carcinoma in situ of the cervix; No psychiatric, addictive, or other disorder that may preclude study

Alabama
      Montgomery Cancer Center, Montgomery,  Alabama,  36106,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Cancer and Blood Institute of the Desert, Rancho Mirage,  California,  92270,  United States
      Providence Saint Joseph Medical Center - Burbank, Burbank,  California,  91505,  United States
Florida
      Hematology-Oncology Associates, PA, Pensacola,  Florida,  32501,  United States
      Mount Sinai Comprehensive Cancer Center, Miami Beach,  Florida,  33140,  United States
      Oncology-Hematology Group of South Florida, Miami,  Florida,  33176,  United States
      Southeast Florida Hematology-Oncology Group, Fort Lauderdale,  Florida,  33308,  United States
Kansas
      Hutchinson Clinic, P.A., Hutchinson,  Kansas,  67502,  United States
Kentucky
      Hematology/Oncology Care Inc., Crestview Hills,  Kentucky,  41017,  United States
Maine
      Maine Center for Cancer Medicine and Blood Disorders, Scarborough,  Maine,  04074,  United States
Maryland
      Associates in Oncology and Hematology, Rockville,  Maryland,  20850,  United States
Massachusetts
      North Shore Cancer Center, Peabody,  Massachusetts,  01960,  United States
Michigan
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Lakeland Medical Center - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
Missouri
      Bond Clinic, Rolla,  Missouri,  65401,  United States
      Midwest Hematology Oncology Consultants, Ltd., Saint Louis,  Missouri,  63136,  United States
New Jersey
      Hematology Oncology Associates, Morristown,  New Jersey,  07962,  United States
New Mexico
      New Mexico Oncology-Hematology, Albuquerque,  New Mexico,  87109,  United States
New York
      HemOnCare, P.C., Brooklyn,  New York,  11235,  United States
      Our Lady of Mercy Medical Center, Bronx,  New York,  10466,  United States
North Carolina
      N.W. Carolina Oncology & Hematology, P.A., Hickory,  North Carolina,  28603,  United States
Ohio
      Oncology/Hematology Care, Inc., Cincinnati,  Ohio,  45219,  United States
Tennessee
      University of Tennessee, Memphis, Memphis,  Tennessee,  38163,  United States
Utah
      Intermountain Hematology/Oncology Associates, Inc., Salt Lake City,  Utah,  84124,  United States
Vermont
      Vermont Center for Cancer Medicine, Inc., Colchester,  Vermont,  05446,  United States
Virginia
      Hematology & Oncology Associates of Virginia, Richmond,  Virginia,  23226,  United States

Study chairs or principal investigators

Carol Brannan,  Study Chair,  Amgen   

Study ID Numbers:  CDR0000067940; AMGEN-GCSF-990756; NCI-V00-1593
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00005959
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08