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

This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), October 2008

Sponsors and Collaborators: Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00068250
  Purpose

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: This phase I/II trial is studying the side effects and best dose of temozolomide when given together with methotrexate and rituximab followed by radiation therapy and to see how well they work in treating patients with primary central nervous system lymphoma.


Condition Intervention Phase
Lymphoma
Drug: methotrexate
Drug: rituximab
Drug: temozolomide
Procedure: radiation therapy
Phase I
Phase II

MedlinePlus related topics:   Cancer    Lymphoma   

ChemIDplus related topics:   Methotrexate    Temozolomide    Rituximab   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity rate (Phase I) [ Designated as safety issue: Yes ]
  • Overall survival rate at 2 years (Phase ll) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pre-irradiation chemotherapy tumor response rate (Phase II) [ Designated as safety issue: No ]
  • Progression-free survival (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment:   64
Study Start Date:   July 2003
Estimated Primary Completion Date:   April 2005 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

  • 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.
  • 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.
  • Compare the tumor response rates of patients treated with this chemotherapy regimen before radiotherapy to that of patients treated on RTOG-9310.
  • Determine the progression-free survival of patients treated with this regimen.
  • Determine the acute and long-term neurologic toxicity of this regimen in these patients.
  • Determine the quality of life of patients treated with this regimen.

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, 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.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

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/mm^3
  • Platelet count at least 100,000/mm^3

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 or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • 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

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
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068250

Show 28 study locations  Show 28 Study Locations

Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)

Investigators
Study Chair:     Jon Glass, MD     Kimmel Cancer Center (KCC)    
  More Information


Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000301563, RTOG-0227
First Received:   September 10, 2003
Last Updated:   October 8, 2008
ClinicalTrials.gov Identifier:   NCT00068250
Health Authority:   Unspecified

Keywords provided by National Cancer Institute (NCI):
primary central nervous system lymphoma  

Study placed in the following topic categories:
Folic Acid
Antibodies, Monoclonal
Lymphatic Diseases
Antibodies
Immunoproliferative Disorders
Rituximab
Methotrexate
Lymphoproliferative Disorders
Temozolomide
Lymphoma
Central nervous system lymphoma, primary

Additional relevant MeSH terms:
Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Reproductive Control Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Abortifacient Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 10, 2008




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