Treating Patients With Recurrent PCNSL With Carboplatin/BBBD and Adding Rituxan To The Treatment Regimen
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00074165|
Recruitment Status : Terminated (Lack of accrual)
First Posted : December 11, 2003
Results First Posted : November 16, 2011
Last Update Posted : April 21, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Brain and Central Nervous System Tumors Drug/Agent Toxicity by Tissue/Organ Lymphoma Thrombocytopenia||Drug: Rituxan Drug: Cyclophosphamide Drug: Etoposide Drug: Etoposide phosphate Drug: Carboplatin Drug: Sodium thiosulfate Drug: Neupogen Drug: Neulasta Drug: Cytarabine||Phase 2|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial Involving Patients With Recurrent PCNSL Treated With Carboplatin/BBBD, by Adding Rituxan (Rituximab), An Anti CD-20 Antibody, To The Treatment Regimen|
|Study Start Date :||January 2003|
|Actual Primary Completion Date :||June 2010|
|Actual Study Completion Date :||December 2010|
|Experimental: All subjects||
Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year.
Other Name: Rituximab
Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year
Dose 200mg/m2 x 2 days infused IV; Every 4 weeks for up to one year. Etoposide phosphate may be given instead.
Drug: Etoposide phosphate
Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead.
Dose: 200mg/m2 x 2 days infused IA with BBBD; Every 4 weeks for up to one year.
Drug: Sodium thiosulfate
Dose: 4 hrs post carboplatin = 20gm/m2;
Dose: 8 hrs post carboplatin = 16gm/m2
Infused IV x 2 days
Other Name: STS
48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. Neulasta (Pegfilgrastim) may be given instead.
Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead.
Other Name: Pegfilgrastim
Dose: 40mg on Day 14 following chemotherapy
- Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years. [ Time Frame: 2 years ]Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions.
- Number of Participants With Overall Survival Assessed by Clinical and Radiographic Response [ Time Frame: 5 years ]Overall survival is measured from entry onto study until death from any cause or until death or progression of disease, respectively.
- Progression-free Survival Assessed by Clinical and Radiographic Response From First Day of Treatment Until Tumor Progression [ Time Frame: 5 years ]
- Quality of Life Assessed by EORTC QOL Before Treatment and Then Every 3 Months [ Time Frame: 5 years ]
- Ototoxicity Assessed by Audiology Hearing Test Done Monthly During Treatment [ Time Frame: 2 years ]
- Effect of Sodium Thiosulfate (STS) on Granulocytes and Erythrocytes Assessed by Complete Blood Count Lab Values Done Weekly During Treatment [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00074165
|United States, Ohio|
|Good Samaritan Hospital Cancer Treatment Center, Hatton Institute|
|Cincinnati, Ohio, United States, 45220|
|United States, Oregon|
|Knight Cancer Institute at Oregon Health and Science University|
|Portland, Oregon, United States, 97239-3098|
|Principal Investigator:||Edward A. Neuwelt, MD||OHSU Knight Cancer Institute|