Colony-Stimulating Factors to Relieve Neutropenia in Patients With Recurrent Non-Hodgkin's Lymphoma

OBJECTIVES: I. Compare the effect of single dose filgrastim-SD/01 vs daily filgrastim (G-CSF)
on the duration of neutropenia in course 1 after combination chemotherapy in patients with
recurrent non-Hodgkin's lymphoma. II. Compare the effect of these regimens on duration of
neutropenia in courses 2-4, absolute neutrophil counts (ANC) in courses 1-4, time to ANC
recovery in courses 1-4, and safety in these patients. III. Determine the pharmacokinetic
profile of these drugs in course 1 in these patients.

OUTLINE: This is a randomized, open label, multicenter study. Patients are randomized to one
of two treatment arms. All patients receive etoposide IV over 1 hour on days 1-4, cisplatin
IV continuously on days 1-4, methylprednisolone IV over 15 minutes on days 1-5, and
cytarabine IV over 2 hours on day 5. Treatment is repeated every 21 days for up to 4 courses.
Arm I: Patients receive filgrastim-SD/01 subcutaneously (SQ) on day 6. Arm II: Patients
receive filgrastim (G-CSF) SQ daily beginning on day 6 and continuing for 12 days or until
blood counts recover.

PROJECTED ACCRUAL: A total of 60 patients (30 per arm) will be accrued for this study within
at least 6 months.

DISEASE CHARACTERISTICS: Diagnosis of non-Hodgkin's lymphoma (NHL) Relapsed disease OR
Refractory to first line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)
chemotherapy No myelodysplastic syndrome or chronic myeloid leukemia

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not
specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at
least 150,000/mm3 Hepatic: Not specified Renal: Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min Other: Not pregnant or nursing Negative
pregnancy test Fertile patients must use effective barrier contraception No other prior
malignancy except: Curatively treated basal cell or squamous cell carcinoma Carcinoma in
situ of the cervix Surgically cured malignancy No hypersensitivity to E. coli derived
products (e.g., filgrastim (G-CSF), insulin, asparaginase)

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow or peripheral blood stem
cell (PBSC) transplantation for NHL No prior filgrastim-SD/01 No other concurrent
myelopoietic growth factors No concurrent WBC transfusions No concurrent PBSC collection
Chemotherapy: See Disease Characteristics No more than 2 prior courses of chemotherapy for
any malignancy Endocrine therapy: No concurrent corticosteroids except topical steroids or
as premedications or associated with chemotherapy Radiotherapy: At least 4 weeks since
prior radiotherapy Surgery: Not specified Other: At least 72 hours since prior
antimicrobials At least 30 days since other prior investigational drug No other concurrent
investigational drug No concurrent prophylactic antibiotics during course 1