Methotrexate and Thiotepa in Treating Patients With Newly Diagnosed Primary CNS Lymphoma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as methotrexate and thiotepa, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining methotrexate with thiotepa in treating patients who have newly-diagnosed primary CNS lymphoma.

Detailed Description
-----------------
OBJECTIVES: Determine the complete radiographic response in patients with newly diagnosed primary CNS lymphoma treated with methotrexate and thiotepa. Determine the duration of progression-free survival and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. Determine whether tumor expression of BCL-6 is associated with response to this chemotherapy regimen and survival of these patients. Describe the relationship between initial response to steroids (if administered), response to this chemotherapy regimen, and survival of these patients. OUTLINE: This is a multicenter study. Patients receive thiotepa IV over 15 minutes on day 1. Patients also receive methotrexate IV over 4 hours on days 1 (8 hours after thiotepa) and 14. Beginning 24 hours after the start of methotrexate infusion, patients receive leucovorin calcium IV or orally every 6 hours until rescue is achieved. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving disappearance of enhancement of disease on MRI receive an additional 28-day course followed by maintenance therapy comprising thiotepa and methotrexate once a month for 11 courses. Patients undergo neuro-ophthalmologic exams annually for 2 years. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 23-39 patients will be accrued for this study within 8-20 months.

Official Title
-----------------
A Phase II Study of Methotrexate and Thiotepa Chemotherapy for Patients With Newly Diagnosed Primary CNS Lymphoma

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Drug: leucovorin calcium
* Drug: methotrexate
* Drug: thiotepa


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed primary CNS lymphoma Confirmed by 1 of the following: Brain biopsy or resection CSF cytology Positive cytology or immunohistochemical diagnosis of monoclonality and measurable intracranial tumor Vitreal biopsy Measurable and contrast-enhancing disease on the postoperative, pretreatment MRI or CT scan No radiographic evidence of ascites or pleural effusions PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic Bilirubin no greater than 2.0 mg/dL SGOT no greater than 4 times upper limit of normal Renal Creatinine no greater than 2 mg/dL Creatinine clearance at least 50 mL/min Other Mini mental score of at least 15 HIV negative Able to achieve hydration No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ No allergy to methotrexate No serious infection No medical illness that would preclude study participation Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy or biologic therapy for this disease Chemotherapy No prior chemotherapy for this disease No other concurrent chemotherapeutic agents Endocrine therapy No prior hormonal therapy for this disease Prior glucocorticoid therapy allowed Radiotherapy No prior radiotherapy for this disease No prior cranial irradiation Surgery See Disease Characteristics Other At least 1 week since prior salicylates, non-steroidal anti-inflammatory drugs, probenecid, folic acid, or sulfonamide medications No other concurrent investigational agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: leucovorin calcium|nan|
|Drug: methotrexate|nan|
|Drug: thiotepa|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete radiographic response |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of progression-free survival and overall survival |  |  | 
| Toxicity |  |  | 
| Association of tumor BCL-6 expression with response |  |  | 
| Relationship among initial response to steroids, response to chemotherapy, and survival |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
primary central nervous system non-Hodgkin lymphoma