RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients with newly diagnosed primary CNS lymphoma.

Condition	Treatment or Intervention	Phase
primary central nervous system lymphoma	Drug: carmustine  Drug: cytarabine  Drug: etoposide  Drug: filgrastim  Drug: melphalan  Drug: methotrexate	Phase II

Further Study Details: 

OBJECTIVES: I. Assess the efficacy and treatment-related toxicity of high-dose chemotherapy comprising carmustine, etoposide, cytarabine, and melphalan followed by autologous peripheral blood stem cell transplantation in patients with primary central nervous system lymphoma. II. Determine the safety of this regimen in these patients. III. Determine the efficacy of this regimen, in terms of 2-year disease-free survival, in these patients. IV. Assess neurologic outcome using serial neurologic examinations in patients treated with this regimen.

PROTOCOL OUTLINE: Induction therapy: Patients receive methotrexate (MTX) IV over 2 hours once on weeks 1, 3, 5, and 7. Patients who respond to treatment receive a fifth dose of MTX on week 9 followed by cytarabine (ARA-C) IV over 3 hours beginning 3 days after completion of MTX infusion and continuing daily for 2 days. Filgrastim (G-CSF) is administered daily beginning 2 days after completion of ARA-C infusion and continuing until harvest of peripheral blood stem cells (PBSC). Patients receive a second course of ARA-C IV beginning 1 month after completion of the first course of ARA-C and continuing daily for 2 days. G-CSF is then administered daily for about 2 weeks. High-dose chemotherapy/transplantation: Patients with stable or responding disease after induction therapy receive high-dose carmustine IV over 1-2 hours on day -7, etoposide IV over 1 hour every 12 hours and ARA-C IV every 12 hours on days -6 to -3, and melphalan IV on day -2. PBSC are reinfused on day 0. Patients receive G-CSF beginning on day 1 and continuing until blood counts recover. Patients are followed monthly for 3 months, every 3 months for 9 months, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 3 years.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed newly diagnosed primary central nervous system (CNS) lymphoma; Patients who have inconclusive biopsy or who are not candidates for biopsy may be eligible provided they have a typical cranial MRI or CT scan (presence of hypo, iso, or hyperdense parenchymal contrast-enhancing mass lesions) to insure that leptomeningeal nonparenchymal lymphomas are not included; Must meet at least one of the following criteria: Positive CSF cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers; Biopsy of the vitreous or uvea demonstrating lymphoma
• Isolated CNS relapse of systemic non-Hodgkin's lymphoma allowed

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: No prior chemotherapy for CNS lymphoma
• Endocrine therapy: Not specified
• Radiotherapy: No prior cranial irradiation
• Surgery: Not specified

--Patient Characteristics--

• Age: Not specified
• Performance status: Not specified
• Life expectancy: At least 8 weeks
• Hematopoietic: WBC at least 4,000/mm3; Platelet count at least 150,000/mm3
• Hepatic: Bilirubin no greater than 2.0 mg/dL; SGOT no greater than 2 times upper limit normal
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 50 mL/min
• Cardiovascular: Ejection fraction at least 50%
• Pulmonary: DLCO at least 50%
• Other: HIV-1 negative; No other active primary malignancy except basal cell skin cancer or carcinoma in situ of the cervix; No prior immunodeficiency (e.g., renal transplantation recipient)

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Lauren E. Abrey,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000066716; MSKCC-98086; NCI-G98-1481
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003632
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08