Freiburg ZNS-NHL Study

Study Overview
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Brief Summary
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The purpose of this study is to determine whether combined chemotherapy [rituximab plus high dosage methotrexate (max. 2 cycles) followed by arabinoside/thiotepa (max. 2 cycles) followed by high dosage carmustin/thiotepa] followed by peripheral blood stem cell transplantation is effective in the treatment of cerebral Non Hodgkin lymphoma [PCNSL].

Official Title
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Freiburg ZNS-NHL Study: Therapy for Patients With Primary Non-Hodgkin Lymphoma of the CNS - Sequential High Dosage Chemotherapy With Autologous Peripheral Blood Stem Cell Plantation

Conditions
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Primary Non Hodgkin Lymphoma of the Central Nervous System

Intervention / Treatment
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* Drug: methotrexate
* Drug: Rituximab
* Drug: Cytarabine
* Drug: Thiotepa
* Drug: Carmustin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: group A: first diagnosis of PCNSL, histologically confirmed group B: relapse or progression of PCNSL after MTX containing chemotherapy age 18 - 65 years not legally incompetent, physically or mentally incapable of giving consent written signed and dated informed consent of the legal representative and - if possible - of the patient Exclusion Criteria: manifestations of further lymphoma outside the CNS sero-positive for HIV severe pulmonary, cardiac, hepatic, renal impairment neutrophil count < 2.000/µl, platelet count < 100.000/µl pulmonary disease with IVC < 55%, DLCO < 40% cardiac ejection fraction < 50%, uncontrolled malign arrhythmia creatinine > 1,5 mg% or creatinine-clearance < 50ml/min bilirubin > 2mg/dl ascites or pleural effusion (> 500ml) pregnancy o r lactation women with childbearing potential without sufficient contraception participation in another clinical trial within the last 30 days prior to the begin or parallel to this study known or current drug or alcohol abuse known hypersensitivity against methotrexate, cytarabine, thiotepa, BCNU rituximab, leukovorin, dexamethasone, neupogen and neulasta.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>first diagnosis of PCNSL: combined chemotherapy with methotrexate | Drug: methotrexate<br>* 8000mg/m2 i.v., max. 2 cycles<br>* Other names: MTX;Drug: Rituximab<br>* 375mg/m2, max. 8 times<br>Drug: Cytarabine<br>* 3000mg/m2 die i.v., 2 days (max. 2 cycles)<br>* Other names: Arabinoside;Drug: Thiotepa<br>* 40mg/m2 i.v. (max. 2 cycles) 2 x 5mg/kg/die i.v. for 2 days<br>Drug: Carmustin<br>* 400mg/m2 i.v. for 1 day<br>* Other names: Bis-Chlorethyl-Nitrosourea;|
| Experimental: B<br>Patients with relapse or progressive disease of PCNSL after methotrexate containing chemotherapy | Drug: Rituximab<br>* 375mg/m2, max. 8 times<br>Drug: Cytarabine<br>* 3000mg/m2 die i.v., 2 days (max. 2 cycles)<br>* Other names: Arabinoside;Drug: Thiotepa<br>* 40mg/m2 i.v. (max. 2 cycles) 2 x 5mg/kg/die i.v. for 2 days<br>Drug: Carmustin<br>* 400mg/m2 i.v. for 1 day<br>* Other names: Bis-Chlorethyl-Nitrosourea;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate |  | 30 days after blood stem cell transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response |  | within 5 years | 
| Overall survival time |  | within 5 years | 
| Neuropsychological state according to Mini-Mental State |  | within 5 years | 
| Neuropsychological assessment (digit span, Hopkins verbal Learning Test-Revised, Trials 1-3, Brief Test of Attention, Trial Making Test, Grooved Pegboard, 6. HVLT-R , EORTC L C30 , EORTC BN20) |  | within 5 years | 
| (Serious) adverse events ([S]AEs) |  | within 30 days after treatment |