NCT01399372

Rituximab, Methotrexate, Vincristine Sulfate, Procarbazine Hydrochloride, and Cytarabine With or Without Radiation Therapy in Treating Patients With Primary Central Nervous System Lymphoma

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 91 (actual)
• Sponsor: Radiation Therapy Oncology Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Chemotherapeutic Agent Toxicity
• Cognitive/Functional Effects
• Lymphoma
• Neurotoxicity
• Radiation Toxicity

Interventions

Type	Name	Description
BIOLOGICAL	Rituximab	One 28-day cycle = 500 mg/m\^2 intravenously on day 1 and day 5.
DRUG	Cytarabine	One 28-day cycle = 3 g/m\^2 intravenously on day 1 and day 2.
DRUG	Methotrexate	One 28-day cycle = 3.5 g/m\^2 intravenously (standard hydration/leucovorin support) on day 2.
DRUG	Procarbazine	One 28-day cycle = 100 mg/m\^2 orally on days 2-8.
DRUG	Vincristine	One 28-day cycle = 1.4 mg/m\^2 intravenously, dose capped at 2.4mg, on day 2 and day 16.
RADIATION	low-dose whole-brain radiation therapy	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.

Timeline

• Start date: 2011-09-01
• Primary completion: 2020-03-19
• Completion: 2022-05-20
• First posted: 2011-07-21
• Last updated: 2023-07-20
• Results posted: 2021-05-13

Locations

45 sites across 2 countries: United States, Israel