Phase II Randomized Study of Rituximab, Methotrexate, Procarbazine, Vincristine, and Cytarabine With and Without Low-Dose Whole-Brain Radiotherapy for Primary Central Nervous System Lymphoma
- To determine median progression-free survival (PFS) in both arms on an intent-to-treat
- 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
- 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
- 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.
- Arm I: Patients receive rituximab IV over 5 hours or per institutional guidelines on
days 1 and 15, methotrexate IV over 2 hours on days 2 and 16, vincristine sulfate IV on
days 2 and 16 (courses 1 and 2 only), and procarbazine hydrochloride orally (PO) on
days 2-8. Treatment repeats every 28 days for 4 courses in the absence of disease
progression or unacceptable toxicity. Patients then receive consolidation therapy
comprising cytarabine IV over 3 hours on days 1-2. Treatment repeats every 28 days for
2 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive rituximab, methotrexate, vincristine sulfate, and procarbazine
hydrochloride as in arm I. After completing chemotherapy (2-5 weeks later), patients
without progressive disease undergo low-dose whole-brain radiotherapy once daily, 5
days a week, for approximately 2.5 weeks (13 fractions total). Patients then receive
consolidation cytarabine as in arm I.
Patients may undergo blood and buccal sample collection for future correlative studies.
Paraffin-embedded tissue block of primary tumor or a core tumor tissue punched from the
tissue block, and cerebrospinal fluid may also be collected.
Patients may also complete the Hopkins Verbal Learning Test-Revised (HVLT-R), the Trail
Making Test Part A and Part B, the Controlled Oral Word Association Test (COWAT), and the
Quality of Life (QOL) questionnaires at baseline and periodically during study.
After completion of study therapy, patients are followed up every 2 months for 2 years and
then every 6 months for 3 years.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression free survival (PFS) defined as the interval from randomization to progression or death, whichever occurs first
From randomization to date of progression, death or last follow-up. Analysis occurs after 67 events (deaths or progression) have been reported.
Antonio Omuro, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|Penrose Cancer Center at Penrose Hospital||Colorado Springs, Colorado 80933|
|West Michigan Cancer Center||Kalamazoo, Michigan 49007-3731|
|Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
|Natalie Warren Bryant Cancer Center at St. Francis Hospital||Tulsa, Oklahoma 74136|
|Medical College of Wisconsin Cancer Center||Milwaukee, Wisconsin 53226|
|Kimmel Cancer Center at Thomas Jefferson University - Philadelphia||Philadelphia, Pennsylvania 19107|
|Cleveland Clinic Taussig Cancer Center||Cleveland, Ohio 44195|
|Maine Center for Cancer Medicine and Blood Disorders - Scarborough||Scarborough, Maine 04074|
|James P. Wilmot Cancer Center at University of Rochester Medical Center||Rochester, New York 14642|
|Baptist Cancer Institute - Jacksonville||Jacksonville, Florida 32207|
|Greenebaum Cancer Center at University of Maryland Medical Center||Baltimore, Maryland 21201|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University||Chicago, Illinois 60611|
|Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center||Boise, Idaho 83706|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida||Tampa, Florida 33612|
|Arizona Oncology Services Foundation||Phoenix, Arizona 85013|
|Integrated Community Oncology Network||Jacksonville Beach, Florida 32250|
|Baptist Medical Center South||Jascksonville, Florida 32258|
|Florida Cancer Center - Palatka||Palatka, Florida 32177|
|Flagler Cancer Center||Saint Augustine, Florida 32086|
|Integrated Community Oncology Network - Orange Park||Orange Park, Florida 32073|
|Integrated Community Oncology Network at Southside Cancer Center||Jacksonville, Florida 32207|
|Memorial Sloan-Kettering Cancer Center - Basking Ridge||Basking Ridge, New Jersey 07920|