Rituximab Followed by Combination Chemotherapy in Treating Patients With Refractory or Recurrent Non-Hodgkin's Lymphoma
Rituximab Followed by Combination Chemotherapy in Treating Patients With Refractory or Recurrent Non-Hodgkin's Lymphoma
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 kill cancer cells. Combining monoclonal antibody therapy
 with chemotherapy may kill more cancer cells.

 PURPOSE: Phase II trial to study the effectiveness of rituximab followed by combination
 chemotherapy in treating patients who have refractory or recurrent non-Hodgkin's lymphoma.
OBJECTIVES: I. Determine the response rate in patients with refractory or recurrent CD20+
 intermediate grade B-cell non-Hodgkin's lymphoma treated with rituximab followed by
 etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH). II. Determine
 the toxicity of the regimen in these patients.

 OUTLINE: This is a multicenter study. Patients receive rituximab IV over 4-10 hours on day 1
 followed by etoposide, vincristine, and doxorubicin IV continuously on days 4-7,
 cyclophosphamide IV over 5-30 minutes on day 8 and oral prednisone on days 4-8. Patients also
 receive sargramostim (GM-CSF) subcutaneously beginning on day 9 until blood counts recover.
 Treatment repeats every 21 days for a maximum of 8 courses in the absence of disease
 progression or unacceptable toxicity.

 PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Diagnosis of intermediate grade B-cell CD20+ non-Hodgkin's
 lymphoma Failed to achieve initial complete response (CR) after at least 2 courses of
 standard chemotherapy OR Relapsed after CR and not eligible for autologous bone marrow
 transplant Measurable disease defined as one of the following: Bidimensionally measurable
 disease at least 2 cm in diameter by radiograph or CT scan Enlarged spleen extending at
 least 2 cm below the costal due to lymphomatous involvement Enlarged liver with focal
 lesions on CT scan or biopsy proven lesions Lymphomatous hepatic involvement must be biopsy
 proven for the liver to be sole area of measurable disease No evidence of CNS involvement 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.

 PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-3 Life expectancy: Not
 specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3* Platelet count at
 least 100,000/mm3* *unless there is bone marrow involvement with lymphoma Hepatic:
 Bilirubin less than 3 mg/dL AST/ALT less than 2 times normal Renal: Creatinine less than
 2.1 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: LVEF greater than
 45% by MUGA or echocardiogram Other: No prior malignancy within the past 10 years except
 squamous cell carcinoma or basal cell carcinoma of the skin or cervical cancer No evidence
 of infection HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients
 must use effective contraception

 PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior rituximab