RATIONALE: Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy and yttrium Y 90 ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma.

Condition	Treatment or Intervention	Phase
stage I adult diffuse large cell lymphoma stage II adult diffuse large cell lymphoma	Drug: cyclophosphamide  Drug: doxorubicin  Drug: prednisone  Drug: rituximab  Drug: vincristine  Drug: yttrium Y 90 ibritumomab tiuxetan  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: isotope therapy  Procedure: monoclonal antibody therapy  Procedure: radiation therapy  Procedure: radioimmunotherapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the complete response (CR) rate and functional CR rate (defined as either CR OR CR/uncertain or partial response by CT scan and positron emission tomography [PET]-negative) in patients with previously untreated stage I (with at least 1 risk factor) or stage II CD20-positive diffuse large cell lymphoma treated with rituximab, prednisone, cyclophosphamide, doxorubicin, and vincristine followed by rituximab and yttrium Y 90 ibritumomab tiuxetan.

Secondary

• Determine the time to treatment failure, duration of response, and overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the toxicity associated with adding involved-field radiotherapy after this regimen in patients with residual disease confirmed by CT or PET scan.

Tertiary

• Determine the development of human anti-mouse antibodies in patients treated with this regimen.
• Determine the pharmacogenetic and pharmacogenomic parameters associated with rituximab in these patients.

OUTLINE: This is a multicenter study.

• Monoclonal antibody (MOAB) therapy/chemotherapy: Patients receive oral prednisone once daily on days 1-5. Patients also receive rituximab IV over several hours followed by cyclophosphamide IV, doxorubicin IV, and vincristine IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) after 2 courses receive 2 additional courses. Patients achieving a partial response or uncertain CR receive 4 additional courses. Patients are evaluated 3 weeks after the last course of therapy. Patients with stable or progressive disease go off study.
• MOAB therapy/radioimmunotherapy: Beginning 4-8 weeks after the last course of MOAB therapy and chemotherapy, patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8.
• Radiotherapy: Patients with residual disease by CT or positron emission tomography scan at 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study within 17 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large cell lymphoma
• Stage I disease, with at least 1 of the following risk factors:
• 60 years of age or older
• Bulky disease (≥ 5 cm unidimensionally)
• Lactic dehydrogenase > upper limit of normal
• ECOG 2
• Stage II disease
• No known CNS lymphoma, testicular lymphoma, or vitreous lymphoma
• No evidence of myelodysplasia on bone marrow aspiration and biopsy

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin < 2.0 mg/dL (3.0 mg/dL if due to liver involvement)

Renal

• Creatinine < 2.0 mg/dL

Cardiovascular

• LVEF > 45%

Other

• No other prior malignancy except treated carcinoma in situ of the cervix, treated squamous cell or basal cell skin cancer, or any other surgically cured malignancy from which the patient has been disease free for at least 3 years
• No other serious medical condition that would preclude study participation
• No active infection that would preclude study participation
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Radiotherapy
• No prior immunotherapy

Chemotherapy

• No prior chemotherapy for another malignancy
• No concurrent chemotherapy for another malignancy

Endocrine therapy

• More than 3 months since prior hormonal therapy for another malignancy
• Prior corticosteroids allowed provided the course was short in duration
• No concurrent hormonal therapy for another malignancy

Radiotherapy

• No prior radioimmunotherapy
• No prior radiotherapy for another malignancy

Surgery

• Not specified

Illinois
      Swedish-American Regional Cancer Center, Rockford,  Illinois,  61104-2315,  United States; Recruiting
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting

Study chairs or principal investigators

Thomas E. Witzig, MD,  Study Chair,  Mayo Clinic Cancer Center   
Ivana Micallef, MD,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000377493; ECOG-E3402; NCT00088881
Record last reviewed:  March 2005
Last Updated:  March 21, 2005
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00088881
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08