Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Alternate Title

High-Dose Methotrexate in Treating Patients With Primary Central Nervous System Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NABTT-9607 JHOC-NABTT-9607, NCI-T97-0049

Objectives

I.    Determine the response rate of primary central nervous system lymphoma 
to induction therapy with systemic methotrexate.

II.   Assess the time to progression, site of relapse, and toxicity of 
systemic methotrexate in patients with primary central nervous system lymphoma.

III.  Assess the survival time and quality of life of this patient population.

Entry Criteria

Disease Characteristics:

Histologically proven primary central nervous system lymphoma of the following
types:
 Non-Hodgkin's B-cell lymphoma by brain biopsy or resection
 Intracranial disease by positive cytology or immunohistochemical diagnosis of
  monoclonality
 Vitreal lymphoma with measurable intracranial tumor

Disease must be confined to eye, brain, leptomeninges, or CSF

Prior/Concurrent Therapy:

Biologic therapy:
 No prior transplant 
  
Chemotherapy:
 No prior chemotherapy for primary central nervous system lymphoma
 No concurrent chemotherapy

Endocrine therapy:
 No concurrent immunosuppressive treatment

Radiotherapy:
 No prior cranial radiotherapy 

Surgery:
 Prior biopsy or resection allowed

Other:
 At least 1 week since salicylates, non-steroidal anti-inflammatory drugs, or
  sulfonamides

Patient Characteristics:

Age:
  18 and over

Performance status:
  Karnofsky 60-100%

Life expectancy:
  At least 2 months

Hematopoietic:
 WBC at least 1500/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin no greater than 2.0 mg/dL
 SGOT/SGPT no greater than 4 times upper limit of normal

Renal:
 Creatinine no greater than 2.0 mg/dL OR
 Creatinine clearance at least 50 mL/min

Other:
 Not allergic to methotrexate
 Not HIV positive
 No preexisting immunosuppression
 Not pregnant or nursing
 No prior malignancy within 5 years except basal cell skin cancer or carcinoma
  in situ of the cervix

Expected Enrollment

A total of 25 patients will be accrued for the study.

Outline

Patients receive induction chemotherapy with high-dose methotrexate 
intravenously every 14 days for 4 to 8 courses of treatment.  Patients with 
complete response receive consolidation therapy with methotrexate for 2 more 
courses, followed by maintenance therapy with monthly methotrexate IV for 11 
months.  Patients not achieving a complete response after 8 courses of 
induction therapy are removed from study.

Quality of life is assessed before treatment, then at 3 and 12 months, and
annually thereafter.  Patients are followed for survival every 2 months or 
until death.

Gerstner ER, Carson KA, Grossman SA, et al.: Long-term outcome in PCNSL patients treated with high-dose methotrexate and deferred radiation. Neurology 70 (5): 401-2, 2008.[PUBMED Abstract]

Gerber DE, Grossman SA, Batchelor T, et al.: Calculated versus measured creatinine clearance for dosing methotrexate in the treatment of primary central nervous system lymphoma. Cancer Chemother Pharmacol 59 (6): 817-23, 2007.[PUBMED Abstract]

Batchelor T, Carson K, O'Neill A, et al.: Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol 21 (6): 1044-9, 2003.[PUBMED Abstract]

Batchelor TT, Hochberg F, O'Neill A, et al.: The treatment of primary central nervous system lymphoma (PCNSL) with methotrexate and deferred radiotherapy: NABTT 96-07. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A616, 2000.

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