Clinical Trial: Methotrexate, Cyclophosphamide, and Etoposide Phosphate Given With Osmotic Blood-Brain Barrier Disruption Plus Dexamethasone and Cytarabine in Treating Patients With Primary CNS Lymphoma

This study is currently recruiting patients.

Sponsors and Collaborators: Oregon Health and Science University
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Drugs used in chemotherapy, such as methotrexate, cyclophosphamide, etoposide phosphate, dexamethasone, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain. Giving methotrexate, cyclophosphamide, and etoposide phosphate with osmotic blood-brain barrier disruption plus dexamethasone and cytarabine may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of giving methotrexate, cyclophosphamide, and etoposide phosphate with osmotic blood-brain barrier disruption plus dexamethasone and cytarabine in treating patients who have primary CNS lymphoma.

Condition Treatment or Intervention Phase
primary central nervous system lymphoma
intraocular lymphoma
 Drug: cyclophosphamide
 Drug: cytarabine
 Drug: dexamethasone
 Drug: etoposide phosphate
 Drug: filgrastim
 Drug: methotrexate
 Drug: pegfilgrastim
 Procedure: biological response modifier therapy
 Procedure: chemotherapy
 Procedure: colony-stimulating factor therapy
 Procedure: cytokine therapy
Phase II

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

Study Type: Interventional
Study Design: Treatment

Official Title: Phase II Study of Methotrexate, Cyclophosphamide, and Etoposide Phosphate Administered in Conjunction With Osmotic Blood-Brain Barrier Disruption and Dexamethasone and Cytarabine in Patients With Primary CNS Lymphoma

Further Study Details: 

OBJECTIVES: Primary

Secondary

  • Determine the ability to recruit an adequate number of patients for this study.
  • Compare progression-free and dementia-free survival with standard measures of overall survival, progression-free survival, disease-free survival, complete response rate, cognitive function, and quality of life of patients treated with this regimen.
  • Determine the feasibility of conducting a future phase III study of this treatment regimen in this patient population.
  • Correlate neuropsychological outcomes with neuroimaging (MRI) outcomes in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive methotrexate (MTX) intra-arterially over 10 minutes, cyclophosphamide IV over 10 minutes, and etoposide phosphate IV over 10 minutes on days 1 and 2 in conjunction with osmotic blood-brain barrier disruption. Patients also receive oral dexamethasone every 6 hours on days 2-15 (followed by a taper) and intraventricular or intrathecal cytarabine on day 14. Beginning 48 hours after the last dose of MTX, patients receive filgrastim (G-CSF)* subcutaneously once daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Alternatively, patients may receive a single dose of pegfilgrastim, administered 24 hours after the completion of chemotherapy

Patients with intraocular lymphoma also receive MTX intravitreally twice weekly until the vitreous is clear of cells by slit lamp exam and then weekly for 1 month and monthly for 1 year.

Quality of life is assessed at baseline, at 6 months, at the completion of treatment, and then every 6 months for 2 years and annually thereafter.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:  16 Years   -   75 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

PATIENT CHARACTERISTICS: Age

  • 16 to 75

Performance status

  • ECOG 0-3 OR
  • Karnofsky 40-100%

Life expectancy

  • Not specified

Hematopoietic

  • Hematocrit at least 25% (transfusion allowed)
  • WBC at least 2,500/mm^3
  • Absolute granulocyte count at least 1,200/mm^3
  • Platelet count at least 100,000/mm^3 OR at least lower limit of normal (transfusion independent)

Hepatic

  • Bilirubin no greater than 2.0 times upper limit of normal

Renal

  • Creatinine clearance at least 30 mL/min

Cardiovascular

  • Adequate cardiac function to tolerate general anesthesia

Pulmonary

  • Adequate pulmonary function to tolerate general anesthesia

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 2 months before and during study participation
  • No other uncontrolled clinically significant confounding medical condition within the past 30 days
  • No known allergy to study agents
  • HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy

  • Not specified

Chemotherapy

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • Single-agent methotrexate administered within the past 14 days allowed

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior cranial or spinal radiotherapy

Surgery


Location and Contact Information


Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
Gene H. Barnett, MD  216-445-1379    barnett@neus.ccf.org 

Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Edward A. Neuwelt, MD  503-494-5626    Neuwelte@ohsu.edu 

Study chairs or principal investigators

Edward A. Neuwelt, MD,  Principal Investigator,  Oregon Health and Science University   

More Information

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

Study ID Numbers:  CDR0000343676; OHSU-5729-2; OHSU-ONC-99055-L; NCT00074178
Record last reviewed:  December 2003
Last Updated:  March 3, 2005
Record first received:  December 10, 2003
ClinicalTrials.gov Identifier:  NCT00074178
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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