Protocol-A: Methotrexate, Procarbazine, Lomustine, Dexamethasone, and Cytarabine in Treating Patients With Primary CNS Lymphoma

Sponsor

OHSU Knight Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00074191

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as methotrexate, procarbazine, lomustine, dexamethasone, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have primary CNS lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: cytarabine Drug: dexamethasone Drug: lomustine Drug: methotrexate Drug: procarbazine hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the toxicity and efficacy of methotrexate, procarbazine, lomustine, dexamethasone, and cytarabine in patients with primary CNS lymphoma.

Secondary

Determine the ability to recruit adequate numbers 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 these patients.
Correlate neuropsychological outcomes with neuroimaging (MRI) outcomes in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter study.

Induction chemotherapy: Patients receive methotrexate IV over 3 hours on days 1, 10, and 20 and intraventricularly or intrathecally (IT) over 5 minutes on days 1, 5, 10, and 15; oral procarbazine on days 1-7; oral lomustine on day 1; oral dexamethasone every 6 hours on days 1-14 followed by a taper (as tolerated); and cytarabine intraventricularly or IT over 5 minutes on days 1, 5, 10, and 15. Treatment repeats every 42 days for a total of 3 courses. Patients with intraocular lymphoma also receive methotrexate intravitreally twice weekly until the vitreous is clear of cells by slit lamp exam. Patients with stable or responding disease proceed to maintenance therapy.
Maintenance chemotherapy: Patients receive methotrexate IV over 3 hours and IT over 5 minutes on day 1; oral procarbazine on days 1-7; oral lomustine on day 1; oral dexamethasone every 6 hours on days 1-14 followed by a taper (as tolerated); and cytarabine intraventricularly or IT over 5 minutes on day 1. Treatment repeats every 42 days for a total of 5 courses.

Patients with intraocular lymphoma also receive methotrexate intravitreally weekly for 1 month and then monthly for 1 year.

Quality of life is assessed at baseline, at 6 months, at the completion of treatment, every 6 months for 2 years, and then 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 180 patients will be accrued for this study within 3 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Combination Chemotherapy (Methotrexate, Procarbazine And CCNU), Intraventricular Cytarabine And Methotrexate, +/- Intra-Ocular Chemotherapy For Patients With Primary Central Nervous System Lymphoma

Study Start Date :

Jan 1, 2000

Actual Primary Completion Date :

Oct 1, 2000

Actual Study Completion Date :

Oct 1, 2000

Outcome Measures

Primary Outcome Measures

Survival as measured by clinical and radiographic response at 5 years following completion of study treatment [5 years]

Secondary Outcome Measures

Overall survival as measured by clinical and radiographic response [5 years]
Progression-free survival as measured by clinical and radiographic response until tumor progression [5 years]
Quality of Life (QOL) as measured by EORTC QOL before and after study treatment, every 6 months for 2 years, and then annually [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed intermediate- or high-grade primary CNS lymphoma documented by brain biopsy or cerebrospinal fluid or vitrectomy analysis
Diagnosed within the past 90 days
No systemic lymphoma NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

16 to 75

Performance status

ECOG 0-3 OR
Karnofsky 40-100%

Life expectancy

Not specified

Hematopoietic

WBC at least 2,500/mm^3
Hematocrit at least 25% (transfusion allowed)
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