Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Primary CNS Lymphoma

Not Applicable

Completed

• Conditions: Brain and Central Nervous System Tumors; Lymphoma
• Interventions: Biological: filgrastim; Biological: rituximab; Drug: cytarabine; Drug: etoposide phosphate; Drug: leucovorin calcium; Drug: methotrexate; Drug: temozolomide

• Registration Number: NCT00416819
• Lead Sponsor: University of California, San Francisco

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This clinical trial is studying the side effects and best ways to give combination chemotherapy together with rituximab in treating patients with newly diagnosed primary CNS lymphoma.

Detailed Description

OBJECTIVES:

Primary

* Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.

Secondary

* Determine the efficacy of this regimen, in terms of the 4-month and 12-month complete and best response rate, in these patients.

* Determine the progression-free and overall survival of patients treated with this regimen.

* Determine the percentage of patients experiencing toxicity or neurotoxicity due to this regimen.

* Determine the treatment-related mortality rate in patients treated with this regimen.

* Document the neurocognitive changes in these patients using the Mini-Mental Status Examination during the first year of treatment with this regimen.

OUTLINE: This is a pilot, multicenter study.

* Induction therapy: Patients receive high-dose methotrexate IV over 4 hours on days 1,15, 29, 43, 57, 71, and 99; leucovorin calcium IV every 6 hours on days 2-4, 16-18, 30-32, 44-46, 58-60, 72-74, and 100-102; oral temozolomide on days 7-11, 35-39, 63-67, 91-95, and 119-123; and rituximab IV on days 3, 17, 31, 45, 59, and 74. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response proceed to consolidation therapy.

* Consolidation therapy I: Beginning 3-4 weeks after completing induction therapy, patients receive high-dose methotrexate IV over 4 hours on day 1, leucovorin calcium IV every 6 hours on days 2-4, and oral temozolomide on days 7-11.

* Consolidation therapy II: Beginning 3-5 weeks after completing consolidation therapy I, patients receive cytarabine IV over 2 hours twice daily and etoposide phosphate IV continuously on days 1-4 and filgrastim (G-CSF) subcutaneously beginning on day 14 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued to this study.

Study Timeline

• Study Start: 2003-09
• Primary Completion: 2005-12
• Study First Submitted: 2006-12-27
• Study First Submitted QC: 2006-12-27
• Study First Posted: 2006-12-28
• Study Completion: 2012-02
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-18
• Last Update Posted: 2015-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
methotrexate, leucovorin calcium, rituximab, and temozolomide	leucovorin calcium	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.
methotrexate, leucovorin calcium, rituximab, and temozolomide	methotrexate	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.
methotrexate, leucovorin calcium, rituximab, and temozolomide	temozolomide	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.
methotrexate, leucovorin calcium, rituximab, and temozolomide	filgrastim	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.
methotrexate, leucovorin calcium, rituximab, and temozolomide	rituximab	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.
methotrexate, leucovorin calcium, rituximab, and temozolomide	etoposide phosphate	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.
methotrexate, leucovorin calcium, rituximab, and temozolomide	cytarabine	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.

Primary Outcome Measures

Name	Time	Method
rate of toxicity in patients with untreated primary CNS lymphoma	up to 8 months	Determine the rate of toxicity, in terms of percentage of patients with grade 4 neurotoxicity, in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.

Secondary Outcome Measures

Name	Time	Method
Efficacy in patients with untreated primary CNS lymphoma treated with induction therapy comprising high-dose methotrexate, leucovorin calcium, rituximab, and temozolomide followed by consolidation therapy comprising cytarabine and etoposide phosphate.	up to 12 months