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

NCT ID: NCT00416819

Last Updated: 2015-08-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-30
• Study Completion Date: 2012-02-29

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.

Conditions

Brain and Central Nervous System Tumors; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

cytarabine

Intervention Type: DRUG

etoposide phosphate

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

Interventions

filgrastim

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

cytarabine

Intervention Type: DRUG

etoposide phosphate

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

temozolomide

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

PATIENT CHARACTERISTICS:

• Karnofsky performance score 50-100%
• HIV negative
• Creatinine clearance ≥ 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No concurrent salicylates, nonsteroidal anti-inflammatory drugs, sulfonamides, or penicillins within the past week

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James L. Rubenstein, MD, PhD

Role: STUDY_CHAIR

University of California, San Francisco

References

Wieduwilt MJ, Valles F, Issa S, Behler CM, Hwang J, McDermott M, Treseler P, O'Brien J, Shuman MA, Cha S, Damon LE, Rubenstein JL. Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res. 2012 Feb 15;18(4):1146-55. doi: 10.1158/1078-0432.CCR-11-0625. Epub 2012 Jan 6.

Reference Type: RESULT

PMID: 22228634 (View on PubMed)

Other Identifiers

UCSF-03301

Identifier Type: -

Identifier Source: secondary_id

UCSF-H9414-23160-02A

Identifier Type: -

Identifier Source: secondary_id

CDR0000458052

Identifier Type: -

Identifier Source: org_study_id