Rituximab&Methotrexate Chemotherapy w/Blood-Brain Barrier Disruption (BBBD) & Sodium Thiosulfate Chemoprotection for Patients With Newly Diagnosed PCNSL
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Chemotherapy drugs such as methotrexate, carboplatin, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as sodium thiosulfate, may protect normal cells from the side effects of chemotherapy. Osmotic blood-brain barrier disruption uses mannitol, to open tight junctions in the blood vessels in the brain and allow methotrexate and carboplatin to be carried to tumor. Giving rituximab together with blood-brain barrier disruption and methotrexate-based chemotherapy may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of carboplatin when given together with rituximab and methotrexate with blood-brain barrier disruption and delayed sodium thiosulfate chemoprotection to see how well they work in treating patients with newly diagnosed primary central nervous system lymphoma.
Primary Central Nervous System Lymphoma
Brain and Central Nervous System Tumors
Drug: Sodium thiosulfate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Patient With Newly Diagnosed Primary Central Nervous System Lymphoma Treated With Methotrexate/BBBD, and Adding Rituximab (an Anti CD-20 Antibody) and Carboplatin, to the Treatment Regimen|
- Complete response rate [ Time Frame: first 3 months of treatment ] [ Designated as safety issue: No ]
- Overall survival at 2 years [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Event-free survival at 2 years [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2005|
|Estimated Study Completion Date:||January 2017|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Rituximab, Methotrexate and Carboplatin
Rituximab (total dose 375mg/m2) will be administered i.v. per institutional guidelines within 24 hours prior to the first BBBD of each monthly course.
Methotrexate 2500 mg/day x 2 days (total dose 5000mg); (1250mg if Creatinine Clearance (CrCl) ≤ 50, but ≥ 30 ml/min) will be infused i.a.. Methotrexate will be infused over 10 minutes in 180 cc normal saline beginning immediately after the mannitol infusion.
carboplatin (200mg/m2/day x 2 days; total dose 400 mg/m2) will be infused i.a.over 10 minutes, in 180 cc of normal saline.
Total dose: 375mg/m2; Every 4 weeks for up to one year.
Other Name: rituximabDrug: Carboplatin
Dose 200mg/m2/day x 2 days; Every 4 weeks for up to one yearDrug: Methotrexate
Dose 2500mg/day x 2 days; Every 4 weeks for up to one yearDrug: Sodium thiosulfate
Dose: 4 hrs post carboplatin = 20gm/m2; Dose: 8 hrs post carboplatin = 16gm/m2
Other Name: STSDrug: Neupogen
48 hrs after last dose of methotrexate, every day (QD) x 7-10 days until white blood cells (WBC) greater than 5000. Dose based on weight of subject. Neulasta (Pegfilgrastim) may be given instead.
Other Names:Drug: Neulasta
Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead.
Other Name: PegfilgrastimDrug: Leucovorin
80mg i.v. at 36 hours after first dose of methotrexate; then 50mg p.o. or i.v. every 6 hours for 20 doses. Additional dosing requirements may apply as clinically indicated.
- Evaluate the safety and toxicities of rituximab in combination with blood-brain barrier disruption with mannitol, combination chemotherapy comprising methotrexate and carboplatin, and delayed sodium thiosulfate.
- Determine the effect of this regimen on complete response (CR) rate within the first 3 months of treatment in these patients.
- Estimate the overall CR response rate, the 2-year overall survival, and the 2-year event-free survival of these patients.
OUTLINE: This is a multicenter, phase I/II study
- Patients receive rituximab IV on day 1 followed by blood-brain barrier disruption comprising mannitol intra-arterially (IA) and combination chemotherapy comprising methotrexate IA over 10 minutes and carboplatin IA over 10 minutes on days 2 and 3. Patients also receive sodium thiosulfate IV over 15 minutes twice on days 2 and 3 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 5 and continuing for approximately 7-10 days or until blood counts recover OR pegfilgrastim SC once on day 5. Patients with positive cerebrospinal fluid (CSF) cytology also receive cytarabine via Ommaya reservoir or lumbar puncture on day 14. Patients with ocular involvement also receive injections of methotrexate and/or rituximab into the eye(s) up to twice a week until the vitreous is clear of cancer cells and then as determined by the ophthalmologist.
- Quality of life is assessed at baseline, every 6 months during treatment, at completion of treatment, and then every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00293475
|Contact: Edward A Neuwelt, MDfirstname.lastname@example.org|
|Contact: Cynthia A Lacy, BSNemail@example.com|
|United States, Oregon|
|Oregon Health and Science University||Recruiting|
|Portland, Oregon, United States, 97239-3098|
|Contact: Edward A Neuwelt, MD 503-494-5626 firstname.lastname@example.org|
|Contact: Cynthia A Lacy, BSN 503-494-5626 email@example.com|
|Principal Investigator: Edward A Neuwelt, MD|
|Principal Investigator:||Edward A. Neuwelt, MD||Oregon Health and Science University|