Rituximab Plus Bendamustine as Front Line Treatment in Frail Elderly (>70 Years) Patients With DLBCL: a Phase II Multicenter Study of the FIL

Study Overview
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Brief Summary
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The purpose of the study is to evaluate feasibility and efficacy of rituximab-bendamustine (R-B)combination in elderly patients affected by diffuse large B-cell lymphoma and defined as frail according to CGA.

Official Title
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Rituximab Plus Bendamustine as Front Line Treatment in Frail Elderly (>70 Years) Patients With Diffuse Large B-cell Non-Hodgkin's Lymphoma: a Phase II Multicenter Study of the Fondazione Italiana Linfomi (FIL)

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Bendamustine+Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven CD20 positive diffuse large B-cell non-Hodgkin's lymphoma Age > 70 years No previous treatment FRAIL patients defined as follows (see Appendices B-E) Age > 80 years with UNFIT profile, i.e. ADL > 5 residual functions IADL > 6 residual functions CIRS 5-8 co-morbidities of grade 2 or Age < 80 years with ADL < 4 residual functions, or IADL < 5 residual functions, or CIRS : 1 co-morbidity of grade 3-4, or > 8 co-morbidities of grade 2 Life expectancy > 6 months Written informed consent Accessibility of patient for treatment and follow up Exclusion Criteria: History of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer Previous exposure to cytotoxic agents Suspect or clinical evidence of CNS involvement by lymphoma HBsAg, HCV or HIV positivity; HBcAb positivity is accepted only with concomitant treatment with Lamivudine AST /ALT > twice upper the normal range; bilirubin > twice upper the normal range; serum creatinine > 2.5 mg /dl Evidence of any severe active acute or chronic infection Concurrent co-morbid medical condition which might exclude administration of full dose chemotherapy Senile dementia 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: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Bendamustine<br>Bendamustine is a novel chemotherapeutic agent, a hybrid of a purine analogue and an alkylator. It shows only partial in vitro cross-resistance with other alkylating agents and it is clinically well tolerated. In fact it has shown to be active in vitro against cell lines which are resistant to other alkylating agents. Preclinical data demonstrate that bendamustine acts in two distinct ways to kill cancer cells: it damages the DNA in cancer cells, which leads to cell death by a process known as apoptosis (programmed cell death) as well as by an alternate cell death pathway known as mitotic catastrophe (a disruption of normal cell division). This dual-effect may be attributable to its unique chemical structure.Bendamustine has demonstrated clinical activity in patients with chronic lymphocytic leukaemia, patients with relapsed indolent NHL, mantle cell lymphoma, multiple myeloma and several solid tumors. | Drug: Bendamustine+Rituximab<br>* Patients will receive : Rituximab 375 mg/m2 intravenously on day 1* Bendamustine 90 mg/m2 intravenously on days 2 and 3** Treatment will be administered on a 28-day cycle basis. Administration of rituximab during cycle 1 is postponed to day 8, thereafter on day 1. After the first cycle, bendamustine can be administered on days 1-2 or days 2-3 according to Institutional/patient/physician choice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the activity of R-B combination in terms of complete response rate (CRR). |  | 4 years | 
| To evaluate the safety and tolerability of R-B combination in terms of rate of adverse events occurrence. |  | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate progression free survival (PFS) |  | 4 years | 
| To evaluate overall survival (OS) |  | 4 years |