Safety and Feasibility Study of Combination of State of Art Chemoimmunotherapy, Intensive Central Nervous System Prophylaxis and Scrotal Irradiation to Treat Primary Diffuse Large B-cell Lymphoma of Testis

Study Overview
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Brief Summary
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This trial is a phase II non-comparative study aimed to determine the feasibility and toxicity of the R-CHOP regimen in combination with intrathecal liposomal cytarabine and systemic intermediate-dose methotrexate followed by loco-regional radiotherapy.

Official Title
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A Phase II Study of R-CHOP With Intensive CNS Prophylaxis and Scrotal Irradiation in Patients With Primary Testicular Diffuse Large B-cell Lymphoma

Conditions
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Large B-cell Diffuse Lymphoma of Testis

Intervention / Treatment
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* Drug: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone, liposomal cytarabine, methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with primary testicular lymphoma at diagnosis. Histological subtype included into the study is only Diffuse Large B Cell Lymphoma (Attachment 2: WHO classification of lymphoma). Orchiectomy is mandatory, before enrolment of the patient into the study. Orchiectomy should be performed within 2 months before study entry. Age 18-80 Untreated patients Ann Arbor Stage IE and IIE. Bilateral testicular involvement at presentation will not be considered Stage IV. These patients may be included into the study and the final Ann Arbor stage (I or II) will be determined by the extent of nodal disease. Bidimensionally measurable or evaluable disease. Patients who have had all disease removed by surgery are eligible. Adequate haematological counts: ANC > 1.0 x 109/L and PLTs count > 75 x 109/L Cardiac ejection fraction ≥ 45% by MUGA scan or echocardiography Non peripheral neuropathy or any active non-neoplastic CNS disease. No other major life-threatening illnesses that may preclude chemotherapy Conjugated bilirubin ≤ 2 x ULN. Alkaline phosphatase and transaminases ≤ 2 x ULN. Creatinine clearances ≥ 45 ml/min. HIV negativity HBV negativity or patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative HCV negativity with the exception of patients with no signs of active chronic hepatitis histologically confirmed Life expectancy > 6 months. Performance status < 2 according to ECOG scale. No psychiatric illness that precludes understanding concepts of the trial or signing informed consent Written informed Consent Exclusion Criteria: Has known or suspected hypersensitivity or intolerance to rituximab History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug) Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis History of clinically relevant hypotension CNS involvement (meningeal and/or brain involvement by lymphoma) Evolving malignancy within 3 years with the exception of localized non-melanomatous skin cancer HIV positivity HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed Active opportunistic infection Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy Exposure to Rituximab prior study entry Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

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: R-CHOP, Depocyte, Methotrexate<br> | Drug: Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone, liposomal cytarabine, methotrexate<br>* Weeks 1-15: 6 cycles of CHOP on Days 1 to 5, to be repeated q21 Days Rituximab 375 mg/m2 on Day 0 or Day 1 of every CHOP cycle IT chemoth:Depocyte 50 mg on Day 0 of cycles 2,3,4&5 of R-CHOP Weeks 18-22: • Methotrexate 1.5 g/m2 q14 Days x 2 From Week 24: • Scrotal prophylactic radiotherapy or involved field radiotherapy(but can be planned concomitantly to R-CHOP in pts with bilateral disease)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events assessments |  | throughout the active treatment period until 30 days after the last drug administration | 
| Activity of the drugs |  | After the 3rd course (and before the 4th) of R-CHOP. Clinical response will be re-assessed at the end of planned treatment, one-two month after the completion of the whole therapy, including radiotherapy In the follow up period every 6 months |