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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00045539
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 24, 2013
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

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.

Condition or disease Intervention/treatment Phase
Lymphoma Drug: leucovorin calcium Drug: methotrexate Drug: thiotepa Phase 2

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Methotrexate and Thiotepa Chemotherapy for Patients With Newly Diagnosed Primary CNS Lymphoma
Study Start Date : October 2002
Actual Study Completion Date : January 2006

Primary Outcome Measures :
  1. Complete radiographic response

Secondary Outcome Measures :
  1. Duration of progression-free survival and overall survival
  2. Toxicity
  3. Association of tumor BCL-6 expression with response
  4. Relationship among initial response to steroids, response to chemotherapy, and survival

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • Karnofsky 60-100%

Life expectancy

  • Not specified


  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3


  • Bilirubin no greater than 2.0 mg/dL
  • SGOT no greater than 4 times upper limit of normal


  • Creatinine no greater than 2 mg/dL
  • Creatinine clearance at least 50 mL/min


  • 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


Biologic therapy

  • No prior immunotherapy or biologic therapy for this disease


  • No prior chemotherapy for this disease
  • No other concurrent chemotherapeutic agents

Endocrine therapy

  • No prior hormonal therapy for this disease
  • Prior glucocorticoid therapy allowed


  • No prior radiotherapy for this disease
  • No prior cranial irradiation


  • See Disease Characteristics


  • At least 1 week since prior salicylates, non-steroidal anti-inflammatory drugs, probenecid, folic acid, or sulfonamide medications
  • No other concurrent investigational agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00045539

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United States, Alabama
Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3410
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Sponsors and Collaborators
New Approaches to Brain Tumor Therapy Consortium
National Cancer Institute (NCI)
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Study Chair: Tracy Batchelor, MD, MPH Massachusetts General Hospital
Layout table for additonal information Identifier: NCT00045539    
Other Study ID Numbers: CDR0000256605
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 24, 2013
Last Verified: December 2005
Keywords provided by National Cancer Institute (NCI):
primary central nervous system non-Hodgkin lymphoma
Additional relevant MeSH terms:
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Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protective Agents