A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This is a prospective, multicenter phase II trial designed to determine efficacy and safety of a chemoimmunotherapy with the combination of Bendamustine + Rituximab in patients with advanced untreated Indolent non Follicular non-Hodgkin Lymphomas (INFL).

Detailed Description
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This is a prospective, multicenter phase II trial designed to determine efficacy and safety of a chemoimmunotherapy with the combination of Bendamustine + Rituximab in patients with advanced untreated Indolent non Follicular non-Hodgkin Lymphomas (INFL). The study includes and induction phase and a consolidation phase.

Official Title
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A Phase II Study of Bendamustine in Combination With Rituximab as Initial Treatment for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma

Conditions
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Indolent Non-follicular, Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Understand and voluntarily sign an informed consent form Histological (bone marrow or lymph nodes biopsy) proven diagnosis of B-cell CD20- positive non-follicular NHL according to REAL/WHO Classification: i. small lymphocytic lymphoma-SLL (bone marrow or lymph nodes biopsy ii. lymphoplasmacytic/citoid lymphoma/ Waldenstrom macroglobulinemia(bone marrow or lymph nodes biopsy) iii. nodal marginal zone lymphoma (lymph nodes biopsy) Untreated patients Stage III or IV or stage II with more than three involved sites Presence of at least one of the following criteria for the definition of active disease: Systemic symptoms Hemoglobin less than 10 g/dL (due to lymphoma) Platelets less than 100 x 10 9/L (due to lymphoma) Diffuse bone marrow infiltrate Lymphocyte doubling time less than 12 months (in leukemic cases) Bulky disease (>7 cm) Aged 18 - 75 Life expectancy >6 months ECOG performance status 0-2 LVEF ≥45% or FS ≥37% ANC ≥1 x 10 9/l and Platelets count ≥75 x 10 9/l, unless due to bone marrow involvement by follicular lymphoma Creatinine up to 1.5 x ULN Conjugated bilirubin up to 2 x ULN Alkaline phosphatase and transaminases up to 2 x ULN Written informed content Exclusion Criteria: Patients with diagnosis of marginal zone lymphoma of splenic or MALT origin Patients with diagnosis of typical Chronic Lymphocytic Leukemia (CLL) Men not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy History of other malignancies within 3 years prior to study entry except for: adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage, localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent Medical condition requiring long term use (>1 months) of systemic corticosteroids Active bacterial, viral, or fungal infection requiring systemic therapy Concurrent medical condition which might exclude administration of therapy Cardiac insufficiency (NYHA grade III/IV) Myocardial infarction within 6 months of entry on study Severe chronic obstructive pulmonary disease with hypoxemia Severe diabetes mellitus difficult to control with adequate insulin therapy Hypertension that is difficult to control Impaired renal function with creatinine clearance <30 ml/min HIV positivity HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive(these patientes need to receive prophylaxis with Lamivudine) HCV positivity with the exception of patients with HCV RNA negative. CNS involvement by lymphoma Participation at the same time in another study in with investiogational drugs are used Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent Women in pregnancy or breastfeeding

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab - Bendamustine (RB)<br>1 arm: Rituximab - Bendamustine (RB) 1 arm for all patients | Drug: Bendamustine<br>* INDUCTION PHASE Rituximab - Bendamustine (RB): cycles 1 to 4 (0, 4, 8, 12 week): Rituximab: 375 mg/sqm iv, day 1* Bendamustine: 90 mg/sqm iv, days 1-2 or days 2-3 according to istitutional/patient/physician choice Repeat cycles every 28 days for a total of 4 cycles *In cycle 1, in order to avoid tumor lysis syndrome, Rituximab will be given on day 8. CONSOLIDATION PHASE Rituximab - Bendamustine (RB): cycles 5 to 6 (16, 20 week): Rituximab: 375 mg/sqm iv day 1 Bendamustine: 90 mg/sqm iv days 1-2 or days 2-3 according to istitutional/patient/physician choice Rituximab two monthly doses Rituximab: 375 mg/sqm iv week 24 and 28<br>* Other names: RIBOMUSTIN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate (CR) | Evaluated at the end of treatment | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety analysis | Evaluated during and at the end of treatment. Percentage of patients with adverse, hematological and non-hematological toxic events | 5 months | 
| Overall response rate (ORR) | Evaluated at the end of treatment. Complete plus partial remission. | 5 months | 
| Overall survival (OS) | Dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method. | at 2 years | 
| Progression free survival (PFS) | Progression, relapse or dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method. | at 2 years | 
| Disease free survival (PFS) | Relapse or dead for any causes from the end of treatment, for patients in CR after B+R. Evaluated by means of Kaplan-Meier method. | at 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INFL, Indolent non-follicular, untreated INFL