RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, vincristine sulfate, procarbazine hydrochloride, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill cancer cells. It is not yet know whether rituximab and combination chemotherapy are more effective when given with or without radiation therapy in treating patients with primary central nervous system lymphoma. PURPOSE: This randomized phase II trial studies how well giving rituximab and combination chemotherapy with or without radiation therapy works in treating patients with primary central nervous system lymphoma.
OBJECTIVES: Primary * To determine median progression-free survival (PFS) in both arms on an intent-to-treat basis. Secondary * To determine overall survival (OS) defined as the interval from randomization to death due to any cause. * To determine treatment-related neurotoxicity rates and disease-related cognitive deterioration in each arm, through the following methods: prospective formal neuropsychological evaluation, utilizing competing-risk methodology to account for death as a competing risk to neurotoxicity or cognitive deterioration from relapsed tumor burden/salvage treatment and incidence of clinically defined neurotoxicity as per investigator's assessment. * To determine if there exists differences between the two treatment arms in terms of health-related quality-of-life and symptoms over time. * To determine response (partial response (PR) and complete response (CR)) rate after methotrexate-based chemotherapy and after consolidation whole-brain radiotherapy (WBRT). * To determine chemotherapy-related toxicity, measured by Common Toxicity Criteria for Adverse Effects (CTCAE), v.4.0. OUTLINE: This is a multicenter study. Patients are stratified according to Memorial Sloan-Kettering Cancer Center recursive-partitioning analysis (RPA) classification for primary central nervous system lymphoma on age and Karnofsky performance status (KPS) (Class 1: age ≤ 50 years vs Class 2: age \> 50 years and KPS ≥ 70% vs Class 3: age \> 50 years and KPS \< 70%). Patients are randomized to 1 of 2 treatment arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
91
One 28-day cycle = 500 mg/m\^2 intravenously on day 1 and day 5.
One 28-day cycle = 3 g/m\^2 intravenously on day 1 and day 2.
One 28-day cycle = 3.5 g/m\^2 intravenously (standard hydration/leucovorin support) on day 2.
One 28-day cycle = 100 mg/m\^2 orally on days 2-8.
One 28-day cycle = 1.4 mg/m\^2 intravenously, dose capped at 2.4mg, on day 2 and day 16.
Total dose of 2340 cGy administered as 13 daily fractions of 180 cGy over 3 weeks. Participants with progressive disease on magnetic resonance imaging (MRI) do not receive WBRT.
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
The Kirklin Clinic at Acton Road
Birmingham, Alabama, United States
Saint Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
Arizona Oncology-Deer Valley Center
Phoenix, Arizona, United States
Arizona Oncology Services Foundation
Scottsdale, Arizona, United States
Progression-free Survival
Progression is defined as any of the following: more than 25% increase in the contrast-enhancing lesion seen on magnetic resonance imaging (MRI) compared with baseline or best response; new site of disease (central nervous system or systemic); recurrent or new ocular disease; recurrent or positive cerebrospinal fluid (CSF) cytology. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.3 years.
Overall Survival
Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method.
Time frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 7.3 years.
Percentage of Participants Experiencing Partial Response or Complete Response
Response was evaluated using the international criteria proposed by the International Primary Central Nervous System Lymphoma (PCNSL) Study Group criteria. Complete Response was defined as no contrast brain enhancement on magnetic resonance imaging (MRI), no corticosteroid use for at least 2 weeks, a normal eye exam, and negative CSF cytology. Partial response was defined as at least 50% decrease in enhancing tumor on MRI compared with baseline imaging, no or minor retinal pigment epithelium (RPE) abnormality, and negative CSF cytology.
Time frame: After 4th cycle of chemotherapy, approximately 4 months after randomization.
Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Global Health Status is calculated from two questions on the EORTC QLQ-C30. The question responses range from 1 "very poor" to 7 "excellent" such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). Data through five years after end of protocol treatment is included in the analysis, while summary data is provided only through three years due to very few participants after that timepoint.
Time frame: EORTC QLQ-C30 was administered at baseline, after cycle 4 of treatment (4 months), then every six months after end of treatment (7 months) for five years.
Percentage of Participants With Neurocognitive Failure
Neurocognitive failure is defined as cognitive failure on two or more of the following tests: Hopkins Verbal Learning Test - Revised (HVLT-R) Free Recall, HVLT-R Delayed Recall, HVLT-R Delayed Recognition, Trail Making Test Part A, Trail Making Test Part B, and Controlled Oral Word Association. Cognitive failure for each test is defined as a change from baseline in raw score (post baseline score - baseline score) at or exceeding the minimally important difference reported in the literature \[determined by the reliable change index (RCI) method\] of -5, -3, -2,12, 26, and -12, respectively, indicating a worsening of neurocognitive function. Time to neurocognitive failure is defined as time from randomization to date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method and the distributions of failure times are compared between the arms. Two-year estimates are provided here.
Time frame: Neurocognitive function tests were administered at baseline, after cycle 4 of treatment (4 months), then every six months after end of treatment (7 months) for five years. Two-year rates are provided here.
Distribution of Participants by Highest Grade Adverse Event Related to Protocol Treatment
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. Adverse events reported as definitely, probably, or possibly related to protocol treatment are considered to be related to treatment.
Time frame: At the end of each chemotherapy 28-day cycle, then every 2 months for two years starting 4 weeks after treatment, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 7.3 years.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Fresno Cancer Center
Fresno, California, United States
Kaiser Permanente-Rancho Cordova Cancer Center
Rancho Cordova, California, United States
Rohnert Park Cancer Center
Rohnert Park, California, United States
The Permanente Medical Group-Roseville Radiation Oncology
Roseville, California, United States
South Sacramento Cancer Center
Sacramento, California, United States
...and 35 more locations