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

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00416819

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Arm

101

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Lymphoma	Biological: filgrastim Biological: rituximab Drug: cytarabine Drug: etoposide phosphate Drug: leucovorin calcium Drug: methotrexate Drug: temozolomide	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: A Pilot Study

Study Start Date :

Sep 1, 2003

Actual Primary Completion Date :

Dec 1, 2005

Actual Study Completion Date :

Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: methotrexate, leucovorin calcium, rituximab, and 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.	Biological: filgrastim Biological: rituximab Drug: cytarabine Drug: etoposide phosphate Drug: leucovorin calcium Drug: methotrexate Drug: temozolomide

Arm

Intervention/Treatment

Experimental: methotrexate, leucovorin calcium, rituximab, and 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.

Biological: filgrastim

Biological: rituximab

Drug: cytarabine

Drug: etoposide phosphate

Drug: leucovorin calcium

Drug: methotrexate

Drug: temozolomide

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed untreated primary CNS lymphoma (PCNSL) confirmed by 1 of the following methods:
Brain biopsy or resection
Patients diagnosed with T-cell PCNSL allowed but will not receive rituximab on study
Cerebrospinal fluid (CSF) cytology
Positive CSF cytology with or without measurable intracranial disease
Vitreal biopsy
Histologic confirmation of vitreal lymphoma with measurable intracranial tumor
No evidence of systemic non-Hodgkin's lymphoma
CT scan of chest, abdomen, and pelvis or bone marrow biopsy negative for extracerebral source of lymphoma
No evidence of pleural effusions or ascites
MRI of brain and spine (plus gadolinium) must have measurable contrast enhancing disease unless CSF cytology is positive