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.

Inclusion criteria

• Diagnosis of non-Hodgkin's lymphoma (NHL)

o Relapsed disease or Refractory to first line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy

• Age 18 and over
• ECOG 0-2Absolute neutrophil count at least 1,500/mm3Platelet count at least 150,000/mm3
• Creatinine not greater than 1.5 mg/dL or Creatinine clearance greater than 60 mL/min
• Fertile patients must use effective barrier contraception
• At least 4 weeks since prior radiotherapy
• At least 72 hours since prior antimicrobials
• At least 30 days since other prior investigational drug

Exclusion criteria

• No myelodysplastic syndrome or chronic myeloid leukemia
• Not pregnant or nursing/Negative pregnancy test
• 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)
• 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
• No more than 2 prior courses of chemotherapy for any malignancy
• No concurrent corticosteroids except topical steroids or as pre-medications or associated with chemotherapy
• No other concurrent investigational drug
• No concurrent prophylactic antibiotics during course 1