Elderly patients with advanced stage previously untreated follicular lymphoma MedDRA version: 14.1 Level: HLT Classification code 10016903 Term: Follicle centre lymphomas, follicular grade I, II, III System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rituximab
Concentration unit: mg milligram(s)
Concentration number: 500-
Pharmaceutical Form: Concentrate for solution
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histological proven diagnosis of B-cell CD20+ follicular NHL, grade I, II and IIIa of WHO Classification 2. Untreated patients with the exception of prior limited radiotherapy 3. Stage III or IV who require therapy according to SIE and GELF criteria (see Appendix A) 4. Stage II with at least one of the following: a. Bulky disease (>7 cm) b. LDH >normal c. Systemic symptoms d. Beta2-Microglobulin >3 mg/l e. Extra-nodal involvement f. 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 10^9/l and Platelets count ≥75 x 10^9/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 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Men not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy 2. 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 3. Medical condition requiring long term use (>1 months) of systemic corticosteroids 4. Active bacterial, viral, or fungal infection requiring systemic therapy 5. Concurrent medical condition which might exclude administration of therapy 6. Cardiac insufficiency (NYHA grade III/IV; see Appendix D) 7. Myocardial infarction within 6 months of entry on study 8. Severe chronic obstructive pulmonary disease with hypoxemia 9. Severe diabetes mellitus difficult to control with adequate insulin therapy 10. Hypertension that is difficult to control 11. Impaired renal function with creatinine clearance <30 ml/min (see Appendix E) 12. HIV positivity 13. HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive (these patients need to receive prophylaxis with Lamivudine) 14. HCV positivity with the exception of patients with no laboratory signs of active chronic hepatitis and HCV-RNA negativity 15. CNS involvement by lymphoma 16. Participation at the same time in another study in which investigational drugs are used 17. Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins 18. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate a statistical benefit in complete remission rate (CR) of a brief chemoimmunotherapy with Rituximab-Bendamustine-Mitoxantrone regimen (4 courses) followed by Rituximab consolidation (4 weekly doses) in elderly patients with advanced stage follicular lymphoma in comparison to historical data in similar patient?s population;Secondary Objective: ?To evaluate the efficacy of the Rituximab-Bendamustine-Mitoxantrone regimen to prolong 2-year progression-free survival (PFS) rate compared to historical standard treatment in elderly patients with advanced stage follicular lymphoma ?To evaluate the rate of molecular response (Bcl2/IgH rearrangement) by qualitative and quantitative PCR after Rituximab-Bendamustine-Mitoxantrone, and its persistence over the follow-up period (Minimal residual disease kinetics) ?To assess the predictive value of qualitative and quantitative PCR on PFS ?To assess the toxicity/safety of this new combination in elderly patients ?To evaluate overall survival of the patients treated with Rituximab-Bendamustine-Mitoxantrone association;Primary end point(s): Tasso di remissione completa | — |
Countries
Italy
Outcome results
None listed