Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NABTT-2109 JHOC-NABTT-2109, NCT00045539

Objectives

1. Determine the complete radiographic response in patients with newly diagnosed primary CNS lymphoma treated with methotrexate and thiotepa.
2. Determine the duration of progression-free survival and overall survival of patients treated with this regimen.
3. Determine the toxicity of this regimen in these patients.
4. Determine whether tumor expression of BCL-6 is associated with response to this chemotherapy regimen and survival of these patients.
5. Describe the relationship between initial response to steroids (if administered), response to this chemotherapy regimen, and survival of these patients.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

A total of 23-39 patients will be accrued for this study within 8-20 months.

Outcomes

Complete radiographic response

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

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.

Trial Contact Information

Trial Lead Organizations

New Approaches to Brain Tumor Therapy

Tracy Batchelor, MD, MPH, Protocol chair		Ph: 617-643-1938; 877-726-5130

Registry Information
Official Title		A Phase II Study of Methotrexate and Thiotepa Chemotherapy for Patients with Newly Diagnosed Primary CNS Lymphoma
Trial Start Date		2002-10-07
Registered in ClinicalTrials.gov		NCT00045539
Date Submitted to PDQ		2002-07-09
Information Last Verified		2005-12-06
NCI Grant/Contract Number		CA-62475

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