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

June 21, 2013 updated by: New Approaches to Brain Tumor Therapy Consortium

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-3410
        • Comprehensive Cancer Center at University of Alabama at Birmingham
    • Florida
      • Tampa, Florida, United States, 33612-9497
        • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory University
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Josephine Ford Cancer Center at Henry Ford Hospital
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Comprehensive Cancer Center at Wake Forest University
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104-4283
        • Abramson Cancer Center of The University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Complete radiographic response

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New Approaches to Brain Tumor Therapy Consortium

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Tracy Batchelor, MD, MPH, Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2002

Primary Completion

December 7, 2022

Study Completion (Actual)

January 1, 2006

Study Registration Dates

First Submitted

September 6, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

June 24, 2013

Last Update Submitted That Met QC Criteria

June 21, 2013

Last Verified

December 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000256605
  • NABTT-2109
  • JHOC-NABTT-2109

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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