Brief Chemoimmunotherapy With R+B+M Followed by R in Elderly Patients Advanced Stage Untreated Follicular 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 brief chemoimmunotherapy with the combination of Rituximab + Bendamustine + Mitoxantrone in elderly patients with advanced stage Follicular Lymphoma.

Official Title
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Brief Induction Chemoimmunotherapy With Rituximab + Bendamustine + Mitoxantrone Followed by Rituximab in Elderly Patients With Advanced Stage Previously Untreated Follicular Lymphoma

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: Rituximab, Mitoxantrone, Bendamustine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proven diagnosis of B-cell CD20+ follicular NHL, grade I, II and IIIa of WHO Classification Untreated patients with the exception of prior limited radiotherapy Stage III or IV who require therapy according to SIE and GELF criteria Stage II with at least one of the following: Bulky disease (>7 cm) LDH >normal Systemic symptoms Beta2-Microglobulin >3 mg/l Extra-nodal involvement Active disease with rapid progression 5.Age from 65 to 80 years, geriatric score FIT (see Appendix B) 6.Life expectancy >6 months 7.ECOG performance status 0-2 (see Appendix C) 8.LVEF ≥45% or FS ≥37% 9.ANC ≥1 x 109/l and Platelets count ≥75 x 109/l, unless due to bone marrow involvement by follicular lymphoma 10.Creatinine up to 1.5 x ULN 11.Conjugated bilirubin up to 2 x ULN 12.Alkaline phosphatase and transaminases up to 2 x ULN 13.Sending of bone marrow sample for Bcl-2/IgH rearrangement evaluation 14.Written informed content Exclusion Criteria: 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 5. Concurrent medical condition which might exclude administration of therapy Cardiac insufficiency (NYHA grade III/IV; see Appendix D) 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 (see Appendix E) HIV positivity HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive (these patients need to receive prophylaxis with Lamivudine) HCV positivity with the exception of patients with no laboratory signs of active chronic hepatitis and HCV-RNA negativity CNS involvement by lymphoma 16. Participation at the same time in another study in which investigational 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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 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: 1<br>Rituximab will be supplied as 375 mg/sqm for i.v.administration.Mitoxantrone will be supplied as 8 mg/sqm for i.v.administration.Bendamustine will be supplied as 90 mg/sqm for i.v.administration. | Drug: Rituximab, Mitoxantrone, Bendamustine<br>* Rituximab will be supplied as 375 mg/sqm for i.v.administration.Mitoxantrone will be supplied as 8 mg/sqm for i.v.administration.Bendamustine will be supplied as 90 mg/sqm for i.v.administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response (CR) Rate at the end of the consolidation phase | Proportion of CR according to the Cheson 2007 response criteria | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS will be measured from the day of enrolment to the date of disease progression, relapse or death due to any cause. | 24 months | 
| Molecular response rate (Bcl2/IgH rearrangement) | Rate of conversion to molecular remission by qualitative and quantitative PCR only in patients with a positive marker at baseline | 24 months | 
| Molecular relapse rate | Rate of conversion to molecular relapse measured by PCR only in patients with a positive marker at baseline | 24 moths | 
| Incidence of grade 3 or greater overall toxicities measured by CTCAE v.3.0 |  | 24 months | 
| Overall survival (OS) | OS will be measured from the day of enrolment to the date of death due to any cause. | 24 moths |