Methotrexate, Cyclophosphamide, and Etoposide Phosphate Given With Osmotic Blood-Brain Barrier Disruption Plus Dexamethasone and Cytarabine in Treating Patients With Primary CNS Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the toxicity and efficacy 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.

      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.
    

Intervention name(s): filgrastim; pegfilgrastim; cyclophosphamide; cytarabine; dexamethasone; etoposide phosphate; methotrexate
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Cytarabine; Dexamethasone; Cyclophosphamide; Methotrexate; Etoposide; Etoposide phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: primary central nervous system lymphoma; intraocular lymphoma