Follicular Lymphoma
Conditions
Brief summary
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.
Interventions
DRUGRituximab, Mitoxantrone, Bendamustine
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
Sponsors
Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
Fondazione Italiana Linfomi - ETS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate at the end of the consolidation phase | 6 months | Proportion of CR according to the Cheson 2007 response criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 24 months | PFS will be measured from the day of enrolment to the date of disease progression, relapse or death due to any cause. |
| Molecular response rate (Bcl2/IgH rearrangement) | 24 months | Rate of conversion to molecular remission by qualitative and quantitative PCR only in patients with a positive marker at baseline |
| Molecular relapse rate | 24 moths | Rate of conversion to molecular relapse measured by PCR only in patients with a positive marker at baseline |
| Incidence of grade 3 or greater overall toxicities measured by CTCAE v.3.0 | 24 months | — |
| Overall survival (OS) | 24 moths | OS will be measured from the day of enrolment to the date of death due to any cause. |
Countries
Italy
Outcome results
None listed