Indolent Non-follicular, Non-Hodgkin's Lymphoma
Conditions
Keywords
INFL, Indolent non-follicular, untreated INFL
Brief summary
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
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.
Interventions
DRUGBendamustine
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
Sponsors
Fondazione Italiana Linfomi - ETS
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Understand and voluntarily sign an informed consent form 2. 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) 3. Untreated patients 4. Stage III or IV or stage II with more than three involved sites 5. Presence of at least one of the following criteria for the definition of active disease: 1. Systemic symptoms 2. Hemoglobin less than 10 g/dL (due to lymphoma) 3. Platelets less than 100 x 10 9/L (due to lymphoma) 4. Diffuse bone marrow infiltrate 5. Lymphocyte doubling time less than 12 months (in leukemic cases) 6. Bulky disease (\>7 cm) 6. Aged 18 - 75 Life expectancy \>6 months 7. ECOG performance status 0-2 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. Written informed content
Exclusion criteria
1. Patients with diagnosis of marginal zone lymphoma of splenic or MALT origin 2. Patients with diagnosis of typical Chronic Lymphocytic Leukemia (CLL) 3. Men not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy 4. 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 5. Medical condition requiring long term use (\>1 months) of systemic corticosteroids 6. Active bacterial, viral, or fungal infection requiring systemic therapy 7. Concurrent medical condition which might exclude administration of therapy 8. Cardiac insufficiency (NYHA grade III/IV) 9. Myocardial infarction within 6 months of entry on study 10. Severe chronic obstructive pulmonary disease with hypoxemia 11. Severe diabetes mellitus difficult to control with adequate insulin therapy 12. Hypertension that is difficult to control 13. Impaired renal function with creatinine clearance \<30 ml/min 14. HIV positivity 15. HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive(these patientes need to receive prophylaxis with Lamivudine) 16. HCV positivity with the exception of patients with HCV RNA negative. 17. CNS involvement by lymphoma 18. Participation at the same time in another study in with investiogational drugs are used 19. Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins 20. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent 21. Women in pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate (CR) | 5 months | Evaluated at the end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety analysis | 5 months | Evaluated during and at the end of treatment. Percentage of patients with adverse, hematological and non-hematological toxic events |
| Overall response rate (ORR) | 5 months | Evaluated at the end of treatment. Complete plus partial remission. |
| Overall survival (OS) | at 2 years | Dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method. |
| Progression free survival (PFS) | at 2 years | Progression, relapse or dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method. |
| Disease free survival (PFS) | at 2 years | 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. |
Countries
Italy
Outcome results
None listed