Study in Patients With Primary Breast Diffuse Large B-cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to clarify the impact of rituximab on clinical outcomes in patients with primary breast diffuse large B-cell lymphoma and also to investigate the role of prophylactic intrathecal chemotherapy using methotrexate for reducing central nervous system (CNS) recurrence.

Detailed Description
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Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare presentation of non-Hodgkin's lymphoma. A significant risk of contralateral breast involvement and a tendency for central nervous system (CNS) progression have been identified in previous studies. Optimal treatment strategies for primary breast DLBCL have remained undefined, although the combination of anthracycline-based chemotherapy and radiotherapy may be considered to be the best treatment option in these studies. However, despite the administration of aggressive treatment, prognosis is still poor, even in localized disease, with 5-year progression-free survival rates of approximately 50% to 65% in most series. Therefore, other therapeutic options must be explored. During the last decade, several studies have shown that rituximab plus CHOP or CHOP-like chemotherapy significantly improves clinical outcomes of patients with DLBCL. However, the relevance of rituximab in the management of this rare extranodal lymphoma has never been studied. Moreover, several studies have also suggested the possibility that prophylactic intrathecal chemotherapy might be effective in reducing CNS recurrence. Thus, this trial is designed to prospectively evaluate the treatment strategy, which addressed the safety and efficacy of a combined therapy that included R-CHOP21 and prophylactic intrathecal chemotherapy using methotrexate.

Official Title
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Multi-center Phase II Study of the Combination of R-CHOP (RItuximab Plus Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) and Prophylactic Intrathecal Chemotherapy With Methotrexate in Patients With CD20+ Primary Breast Diffuse Large B-cell Lymphoma

Conditions
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Large B Cell Diffuse Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Procedure: Prophylactic intrathecal chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed CD20 positive primary breast DLBCL age ≤ 70 No prior chemotherapy or radiotherapy for DLBCL Performance status (ECOG) ≤ 2 Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2D ECHO without clinically significant abnormalities Adequate renal function: serum creatinine level < 2 mg/dL (177 μmol/L) Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value, Bilirubin < 2 X upper normal value Adequate BM functions: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause Life expectancy more than 6 months Informed consent Exclusion Criteria: other subtype primary breast non-Hodgkin's lymphoma than DLBCL secondary breast DLBCL Patients with a known history of HIV seropositivity or HCV (+). Patients who have HBV (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period. Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri Pregnant or lactating women, women of childbearing potential not employing adequate contraception Other serious illness or medical conditions Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry History of significant neurologic or psychiatric disorders including dementia or seizures Active uncontrolled infection (viral, bacterial or fungal infection) Other serious medical illnesses Known hypersensitivity to any of the study drugs or its ingredients (i.e., hypersensitivity to Polysorbate 20, CHO cell products, or recombinant human antibodies) Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy

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

Sexes Eligible for Study
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Female

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: primary breast DLBCL<br>isolated breast involvement with or without nodal disease | Drug: Rituximab<br>* R-CHOP21 consist of rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg/m2, a maximum of 2mg), administered intravenously on day 1 and 100 mg oral prednisone on days 1 through 5.<br>Procedure: Prophylactic intrathecal chemotherapy<br>* Prophylactic intrathecal chemotherapy using methotrexate (12mg total dose) will be performed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival |  | From the date of treatment until the date of disease progression or death from any cause (minimum 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | From the date of treatment until the date of death from any cause (minimum 2 years) | 
| Number of patients with CNS recurrence |  | From the date of treatment until the date of CNS recurrrence (minimum 2 years) | 
| Number of patients with adverse events | safety of a combined treatment of R-CHOP21 and prophylactic intrathecal chemotherapy according to the NCI-CTCAE ver.3.0 | From the first date of treatment until 30 days after the last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary breast diffuse large B cell lymphoma, rituximab, prophylactic intrathecal chemotherapy, CNS recurrence