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

This study is currently recruiting patients.

Sponsors and Collaborators: Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)


RATIONALE: Drugs used in chemotherapy such as methotrexate and temozolomide use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining methotrexate, temozolomide, and rituximab with radiation therapy may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining methotrexate, rituximab, and temozolomide with radiation therapy in treating patients who have primary central nervous system lymphoma.

Condition Treatment or Intervention Phase
primary central nervous system lymphoma
 Drug: methotrexate
 Drug: rituximab
 Drug: temozolomide
 Procedure: antibody therapy
 Procedure: biological response modifier therapy
 Procedure: chemotherapy
 Procedure: monoclonal antibody therapy
 Procedure: radiation therapy
Phase I
Phase II

MedlinePlus related topics:  Cancer;   Cancer Alternative Therapy;   Lymphoma;   Neurologic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: 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

Further Study Details: 


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

  • 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, and then every 3 months for 2 years, every 6 months for 3 years, and annually for 5 years.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: 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.


Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both



  • 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


  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • At least 8 weeks


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


  • 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


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



  • Not specified


  • No prior chemotherapy

Endocrine therapy

  • Not specified



  • No prior organ transplantation

Location and Contact Information

      Foundation for Cancer Research and Education, Phoenix,  Arizona,  85013,  United States; Recruiting
David G. Brachman, MD, FACRO  602-274-4484 

      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033-0804,  United States; Recruiting
Oscar E. Streeter, MD  323-865-3084 

      Baptist-South Miami Regional Cancer Program, Miami,  Florida,  33176-2197,  United States; Recruiting
Andre A. Abitbol, MD  786-596-6566 

      Wendt Regional Cancer Center at Finley Hospital, Dubuque,  Iowa,  52001,  United States; Recruiting
James R. Baer, MD  563-589-2468 

      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States; Recruiting
Contact Person  616-373-7488 

      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
William T. Stephenson, MD  816-823-0555 

      CCOP - Marshfield Clinic Research Foundation, Marshfield,  Wisconsin,  54449,  United States; Recruiting
Tarit Kumar Banerjee, MD, FACP  715-387-5511 

Study chairs or principal investigators

Jon Glass, MD,  Study Chair,  Fox Chase Cancer Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000301563; RTOG-0227; NCT00068250
Record last reviewed:  August 2003
Last Updated:  March 10, 2005
Record first received:  September 10, 2003 Identifier:  NCT00068250
Health Authority: United States: Federal Government processed this record on 2005-04-08

Cache Date: April 9, 2005