Phase II Trial of Combined Modality Treatment in Primary Central Nervous System Lymphoma

Study Overview
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Brief Summary
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Aim of the study is to establish in a prospective, randomized clinical trial the activity of primary chemotherapy containing high dose-methotrexate, alone or combined with high dose cytarabine, in patients with primary central nervous system lymphoma

Official Title
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Randomized Phase II Trial on Primary Chemotherapy With High-dose Methotrexate, Alone or Associated With High-dose Cytarabine, Followed by Response- and Age-tailored Radiotherapy for Immunocompetent Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

Conditions
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Lymphoma, B Cell

Intervention / Treatment
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* Drug: high dose methotrexate
* Drug: high dose cytarabine
* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of non-Hodgkin's lymphoma. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy. Disease exclusively localized into the central nervous system, cranial nerves or eyes. Untreated patients (patients treated with steroids alone are eligible). At least one measurable lesion. Age 18 - 75 years. ECOG performance status < 3 HBsAg-negative and Ab anti-HCV-negative serologic status. No known HIV disease or immunodeficiency. Adequate bone marrow (PLT > 100000 mm3, Hb ≥ 9 g/dl, ANC ≥ 2.000 mm3), renal (creatinine clearance ≥ 60 mL/min), cardiac (VEF ≥ 50%), and hepatic function (total serum bilirubin < 3 mg/dL, AST/ALT and gGT < 2 per upper normal limit value). No previous or concurrent malignancies with the exception of surgically cured cervical intraepithelial neoplasia type 1 (CIN1) or localized non-melanomatous skin cancer and of other cancers without evidence of disease since at least 5 years (patients with a previous lymphoma diagnosis will be excluded). Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Non-pregnant and non-lactating status for female patients. Adequate contraceptive measures during study participation for sexually active patients of childbearing potential. No concurrent treatment with other experimental drugs. Informed consent signed by the patient before registration

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High-dose methotrexate alone<br> | Drug: high dose methotrexate<br> <br> Radiation: radiotherapy<br> <br> |
| Experimental: High-dose methotrexate associated with high dose cytarabine<br> | Drug: high dose methotrexate<br> <br> Drug: high dose cytarabine<br> <br> Radiation: radiotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The main endpoint is the complete remission (CR) rate after chemotherapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  |  | 
| Response duration (time to relapse or progression) for responder patients |  |  | 
| Overall survival |  |  | 
| Event-free survival |  |  | 
| Meningeal relapse rate |  |  | 
| Early and late neurotoxicity |  |  |