Clinical trial NCT00074165
Conditions: Brain and Central Nervous System Tumors Drug/Agent Toxicity by Tissue/Organ Lymphoma Thrombocytopenia
Keywords: drug/agent toxicity by tissue/organ thrombocytopenia intraocular lymphoma primary central nervous system non-Hodgkin lymphoma primary central nervous system Hodgkin lymphoma
Sponsor: OHSU Knight Cancer Institute
Start date: 2003-01-01; Completion date: 2010-12-01
Enrollment: 17 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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, such as carboplatin, cyclophosphamide, etoposide, etoposide phosphate, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain tumor. Chemoprotective drugs such as sodium thiosulfate may protect normal cells from the side effects of carboplatin-based chemotherapy. Combining rituximab with chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate in treating patients who have refractory or recurrent primary CNS lymphoma.

Detailed description:
OBJECTIVES:

Primary

* Determine the efficacy of rituximab, carboplatin, cyclophosphamide, etoposide or etoposide phosphate and cytarabine administered in conjunction with osmotic blood-brain barrier disruption and high-dose sodium thiosulfate, in terms of complete response rate, in patients with refractory or recurrent primary CNS lymphoma.

Secondary

* Determine the overall survival and 2-year progression-free survival of patients treated with this regimen.
* Determine the quality of life and cognitive function of patients treated with this regimen.
* Determine the neurotoxicity of this regimen in these patients.
* Determine the percentage of patients with ototoxicity over time after treatment with this regimen.
* Determine the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on day 1. On days 2 and 3, patients receive carboplatin intra-arterially over 10 minutes, cyclophosphamide IV over 10 minutes, and etoposide or etoposide phosphate IV over 10 minutes in conjunction with blood-brain barrier disruption. Patients also receive high-dose sodium thiosulfate IV over 15 minutes administered 4 and 8 hours after carboplatin on days 2 and 3 and intraventricular or intrathecal cytarabine on day 14. Beginning 48 hours after the last dose of chemotherapy, patients receive filgrastim (G-CSF)\* subcutaneously (SC) daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for up to 12 courses.

NOTE: \* Alternatively, patients may receive a single dose of pegfilgrastim SC, administered 48 hours after the completion of chemotherapy

Patients with intraocular lymphoma also receive methotrexate intravitreally twice weekly until the vitreous is clear of cells by slit lamp exam; once weekly for 1 month; and then monthly for 1 year.

Quality of life is assessed at baseline, every 3 months during treatment, within 30 days of final treatment, then every 6 months for 1 year, and then annually thereafter.

Patients are followed monthly for 3 months, every 2 months for 8 months, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 11-25 patients will be accrued for this study within 7-10 years.

Arms: arm 1: None
Interventions: intervention 1: Rituxan intervention 2: Cyclophosphamide intervention 3: Etoposide intervention 4: Etoposide phosphate intervention 5: Carboplatin intervention 6: Sodium thiosulfate intervention 7: Neupogen intervention 8: Neulasta intervention 9: Cytarabine
Intervention descriptions: intervention 1: Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year. intervention 2: Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year intervention 3: Dose 200mg/m2 x 2 days infused IV; Every 4 weeks for up to one year. Etoposide phosphate may be given instead. intervention 4: Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead. intervention 5: Dose: 200mg/m2 x 2 days infused IA with BBBD; Every 4 weeks for up to one year. intervention 6: Dose: 4 hrs post carboplatin = 20gm/m2;

Dose: 8 hrs post carboplatin = 16gm/m2

Infused IV x 2 days intervention 7: 48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. Neulasta (Pegfilgrastim) may be given instead. intervention 8: Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead. intervention 9: Dose: 40mg on Day 14 following chemotherapy

Protocol documents: