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Last Modified: 11/20/2009     First Published: 8/24/2003  
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Phase I/II Study of Chemotherapy Comprising Methotrexate, Rituximab, and Temozolomide Before Radiotherapy and Temozolomide After Radiotherapy in Patients With Primary Central Nervous System Lymphoma

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

Alternate Title

Combination Chemotherapy, Monoclonal Antibody, and Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase II, Phase ITreatmentActive18 and overNCIRTOG-0227
NCT00068250

Objectives

  1. Determine the maximum tolerated dose of temozolomide in combination with methotrexate and rituximab before fractionated whole brain radiotherapy in patients with primary central nervous system lymphoma.
  2. Compare the 2-year survival rate of patients receiving this chemotherapy regimen before radiotherapy and temozolomide after radiotherapy to that of patients treated on protocol RTOG-9310.
  3. Compare the tumor response rates of patients treated with this chemotherapy regimen before radiotherapy to that of patients treated on RTOG-9310.
  4. Determine the progression-free survival of patients treated with this regimen.
  5. Determine the acute and long-term neurologic toxicity of this regimen in these patients.
  6. Determine the quality of life of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

  • Cytologically confirmed primary CNS lymphoma
    • Based on positive biopsy, cerebrospinal fluid, or vitreous cytology (in association with measurable intraparenchymal tumor)
    • B-cell type
    • CD20+ disease
    • Cytology must demonstrate lymphoma OR an immunohistochemical diagnosis of malignant lymphocytes with a monoclonal lymphocytic population

  • No evidence of systemic lymphoma

Prior/Concurrent Therapy:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy to the brain, head, or neck

Surgery

  • No prior organ transplantation

Patient Characteristics:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • At least 8 weeks

Hematopoietic

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

Hepatic

  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • AST no greater than 2 times ULN
  • Alkaline phosphatase no greater than 2 times ULN
  • No active hepatitis B

Renal

  • Creatinine clearance at least 50 mL/min
  • No renal insufficiency

Other

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV positivity
  • No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No history of idiopathic sensitivity to any of the drugs in this study
  • No active infection
  • No known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of rituximab

Expected Enrollment

64

A total of 52-64 patients (up to 18 patients for phase I and 46 patients for phase II) will be accrued for this study within 19 months.

Outcomes

Primary Outcome(s)

Toxicity rate (Phase I)
Overall survival rate at 2 years (Phase ll)

Secondary Outcome(s)

Pre-irradiation chemotherapy tumor response rate (Phase II)
Progression-free survival (Phase II)

Outline

This is a phase I dose-escalation study of temozolomide in combination with methotrexate and rituximab before radiotherapy, followed by a phase II study.

Phase I

  • Pre-radiotherapy chemotherapy: Patients receive rituximab IV 3 days prior to the first course of methotrexate. Patients then receive methotrexate IV over 4 hours on weeks 1, 3, 5, 7, and 9 (for a total of 5 doses). Patients also receive oral temozolomide daily for 5 days on weeks 4 and 8.

    Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 0 of 3 or 1 of 6 patients experience dose-limiting toxicity.

  • Radiotherapy: Patients undergo whole brain radiotherapy daily for 5 days on weeks 11, 12, and 13.

  • Post-radiotherapy chemotherapy: Patients receive oral temozolomide once daily on days 1-5 beginning at week 14. Treatment repeats every 28 days for 10 courses in the absence of unacceptable toxicity.

Phase II

  • Patients receive treatment as in phase I at the MTD of temozolomide. Treatment continues in the absence of unacceptable toxicity.

Quality of life is assessed at baseline, at weeks 10 and 13, every 2 months during post-radiotherapy temozolomide therapy, at the end of therapy, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

Jon Glass, MD, Protocol chair
Ph: 215-503-7005; 800-533-3669
Email: jon.glass@jefferson.edu

Trial Sites

U.S.A.
Florida
  Jacksonville
 Baptist Cancer Institute - Jacksonville
 Clinical Trials Office - Baptist Cancer Institute - Jacksonville
Ph: 904-202-7051
 Integrated Community Oncology Network at Southside Cancer Center
 Douglas Johnson, MD
Ph: 904-202-2273
  Jacksonville Beach
 Integrated Community Oncology Network
 Douglas Johnson, MD
Ph: 904-202-2273
  Jascksonville
 Baptist Medical Center South
 Douglas Johnson, MD
Ph: 904-202-2273
  Orange Park
 Integrated Community Oncology Network - Orange Park
 Douglas Johnson, MD
Ph: 904-202-2273
  Palatka
 Florida Cancer Center - Palatka
 Douglas Johnson, MD
Ph: 904-202-2273
  Saint Augustine
 Flagler Cancer Center
 Douglas Johnson, MD
Ph: 904-202-2273
Michigan
  Kalamazoo
 Borgess Medical Center
 Raymond Lord, MD
Ph: 269-373-7458
 Bronson Methodist Hospital
 Raymond Lord, MD
Ph: 269-373-7458
 West Michigan Cancer Center
 Clinical Trials Office - West Michigan Cancer Center
Ph: 269-373-7458
Missouri
  Saint Louis
 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
 David Mansur
Ph: 314-747-7222
800-600-3606
Nevada
  Las Vegas
 CCOP - Nevada Cancer Research Foundation
 John Ellerton, MD, CM
Ph: 702-384-0013
Ohio
  Cleveland
 Cleveland Clinic Taussig Cancer Center
 Clinical Trials Office - Cleveland Clinic Taussig Cancer Center
Ph: 866-223-8100
Oregon
  Milwaukie
 Providence Milwaukie Hospital
 Keith Lanier, MD
Ph: 503-299-6500
  Portland
 CCOP - Columbia River Oncology Program
 Keith Lanier, MD
Ph: 503-299-6500
 Providence Cancer Center at Providence Portland Medical Center
 Clinical Trials Office - Providence Cancer Center at Providence Portland Medical Center
Ph: 503-215-6412
 Providence St. Vincent Medical Center
 Clinical Trials Office - Providence St. Vincent Medical Center
Ph: 503-215-6412
Pennsylvania
  Philadelphia
 Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
 Clinical Trials Office - Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Ph: 215-955-6084
South Carolina
  Charleston
 Hollings Cancer Center at Medical University of South Carolina
 Clinical Trials Office - Hollings Cancer Center at Medical University of South Carolina
Ph: 843-792-9321
Utah
  Murray
 Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
 R. Jeffrey Lee, MD
Ph: 801-408-1146
  Provo
 Utah Valley Regional Medical Center - Provo
 Clinical Trials Office - Utah Valley Regional Medical Center - Provo
Ph: 801-357-7965
Washington
  Vancouver
 Southwest Washington Medical Center Cancer Center
 Keith Lanier, MD
Ph: 503-299-6500
Wisconsin
  Menomonee Falls
 Community Memorial Hospital Cancer Care Center
 Christopher Schultz, MD
Ph: 414-805-4472
  Milwaukee
 Medical College of Wisconsin Cancer Center
 Clinical Trials Office - Medical College of Wisconsin Cancer Center
Ph: 414-805-4380
Canada
Ontario
  London
 London Regional Cancer Program at London Health Sciences Centre
 David Macdonald
Ph: 519-685-8615

Registry Information
Official Title Phase I/II Study Of Pre-Irradiation Chemotherapy With Methotrexate, Rituximab, And Temozolomide And Post -Irradiation Temozolomide For Primary Central Nervous System Lymphoma
Trial Start Date 2003-07-22
Trial Completion Date 2010-03-22 (estimated)
Registered in ClinicalTrials.gov NCT00068250
Date Submitted to PDQ 2003-03-25
Information Last Verified 2009-11-20
NCI Grant/Contract Number CA21661

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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