Temozolomide, Nedaplatin, Vincristine, and Radiotherapy as First-line Treatment in Newly Diagnosed Primary CNS Lymphoma

Study Overview
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Brief Summary
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In this trial, we will treat newly diagnosed PCNSL with temozolomide, nedaplatin, vincristine (TNV) as the replacement of high-dose methotrexate to combine with concurrent chemoradiotherapy. Our objective was to assess our treatment strategies' availability based on response rates, progression-free survival (PFS), median PFS, and toxicity.

Detailed Description
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The best reported outcomes of PCNSL treatment are high-dose methotrexate-based chemotherapy combined with whole-brain radiation therapy (WBRT). Despite aggressive therapy, however, nearly 50% of patients will relapse within 24 months of diagnosis. Furthermore, the application of high-dose methotrexate-based regimen is complex, needing be hydrated, alkalified and detoxified, and treatment-related toxicity mortality is severe[3,4]. In an attempt to improve upon these poor results and reduce treatment-related side effects, we will treat about 15-20 PCNSL patients with temozolomide concurrent chemoradiotherapy at the outset and then adjuvant chemotherapy for 6 cycles with temozolomide, nedaplatin, vincristine, as part of front-line therapy. Our objective is to assess our treatment strategies' availability based on response rates, progression-free survival (PFS), median PFS, and toxicity.

Official Title
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Phase Ⅱ Trial of Temozolomide Plus Concurrent Whole-Brain Radiation Followed by TNV Regimen as Adjuvant Therapy for Patients With Newly Diagnosed Primary Central Nervous System (CNS) Lymphoma (PCNSL)

Conditions
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Central Nervous System Tumors

Intervention / Treatment
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* Radiation: Radiotherapy
* Drug: nedaplatin
* Drug: vincristine
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary CNS lymphoma. Newly diagnosed. ECOG (Eastern Cooperative Oncology Group) Performance status of 0-1. Relevant hospital examination including laboratory examination and physical examination (Chest X-ray, electrocardiogram, abdomen B ultrasonography, magnetic resonance imaging (MRI) of head and neck) must to be done, in order to exclude other system fatal diseases. Must have adequate organ function as defined by the protocol: Adequate renal function: serum creatinine ≤ 1.5 mg/dl and/or calculated creatinine clearance ≥ 60 ml/min; Adequate hepatic function: bilirubin level ≤ 1.5 x ULN, ASAT & ALST ≤ 1.5 x ULN.Adequate bone marrow reserves: neutrophil (ANC) count ≥ 1500 /mm^3, platelet count ≥ 100,000 /mm^3, hemoglobin ≥ 9 g/dl. Age >/= 18 and </= 75 years Signed written informed consent prior to study entry. Exclusion Criteria: Patients with human immunodeficiency virus seropositivity and systemic lymphoma manifestation. Serious uncontrolled concurrent illness. Previous brain radiotherapy, systemic chemotherapy. Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol. Any evidence of prior exposure to Hepatitis B virus. Unable to comprehend the study requirements or who are not likely to comply with the study parameters. Pregnant (confirmed by serum or urine β-HCG) or lactating.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide, Nedaplatin, Vincristine, Radiotherapy<br>The newly diagnosed PCNSL patients will be given concurrent temozolomide (75mg/m2, orally) daily during WBRT. Then, the TNV regimen will be given after four weeks. TNV regimen consisted of temozolomide (200mg/m2 orally, days 1-5), nedaplatin (80mg/m2 i.v., day 1), vincristine (1.4mg/m2 i.v., day 1). Each cycle was 4 weeks and a maximum of six cycles were applied. | Radiation: Radiotherapy<br>* WBRT was given five times a week at 2 gray (Gy)/d until the whole brain radiotherapy dose reached 40 gray. The patients were given concurrent temozolomide (75mg/m2, orally) daily during radiotherapy until the end of radiotherapy.<br>* Other names: Concurrent Chemoradiotherapy;Drug: nedaplatin<br>* nedaplatin (80mg/m2 i.v., day 1), 28 day schedule, performed four weeks after radiotherapy.A maximum of six cycles were applied.<br>Drug: vincristine<br>* vincristine (1.4mg/m2 i.v., day 1)28 day schedule,performed four weeks after radiotherapy.A maximum of six cycles were applied.<br>* Other names: ao-xian-da;Drug: Temozolomide<br>* Temozolomide (200mg/m2 orally, days 1-5, Each cycle was 4 weeks ), performed four weeks after radiotherapy. A maximum of six cycles were applied.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete radiologic response (CR) | final data collection date for primary outcome measure | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival |  | 3 years | 
| Toxicity |  | 3 years | 
| Overall response rate |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma