Clinical trial NCT01929265: A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma
Official title: A Phase II Study of Bendamustine in Combination With Rituximab as Initial Treatment for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Indolent Non-follicular
Non-Hodgkin's Lymphoma
Keywords: INFL
Indolent non-follicular
untreated INFL
Lead sponsor: Fondazione Italiana Linfomi - ETS
Sponsor class: OTHER
First posted: 2013-08-27
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Complete remission rate (CR)
timeFrame: 5 months
Secondary outcomes:
measure: Safety analysis
timeFrame: 5 months
measure: Overall response rate (ORR)
timeFrame: 5 months
measure: Overall survival (OS)
timeFrame: at 2 years
measure: Progression free survival (PFS)
timeFrame: at 2 years
measure: Disease free survival (PFS)
timeFrame: at 2 years
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: SC Ematologia - AO SS. Antonio e Biagio e C. Arrigo
state: AL
city: Brescia
country: Italy
facility: SC Ematologia Spedali Civili
state: BS
city: Bolzano
country: Italy
facility: Divisione di Ematologia e Trapianti, Ospedale San Maurizio
state: BZ
city: San Giovanni Rotondo
country: Italy
facility: Divisione di Ematologia, Centro Trapianto di Cellule Staminali
state: Foggia
city: Genova
country: Italy
facility: Divisione Ematologia I , Ospedale San Martino
state: GE
city: Messina
country: Italy
facility: S.C. Ematologia Azienda Ospedaliera Papardo
state: ME
city: Rozzano
country: Italy
facility: Divisione di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas
state: Milano
city: Milano
country: Italy
facility: Divisione di Ematologia Ospedale Niguarda
state: MI
city: Modena
country: Italy
facility: Centro Oncologico Modenese
state: MO
city: Palermo
country: Italy
facility: Ematologia Azienda Ospedaliero Universitaria Paolo Giaccone
state: PA
city: Aviano
country: Italy
facility: Div. Oncologia Medica - CRO, Centro di Riferimento Oncologico
state: PN
city: Milano
country: Italy
facility: UOC Ematologia 1/CTMO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Napoli
country: Italy
facility: Oncoematologia Istituto Pascale
city: Novara
country: Italy
facility: S.C.D.U Ematologia Azienda Ospedaliero Universitaria Maggiore
city: Pavia
country: Italy
facility: UO Ematologia Università - Policlinico San Matteo
city: Pescara
country: Italy
facility: Ematologia Ospedale Santo Spirito
city: Piacenza
country: Italy
facility: UOA Ematologia, Ospedale Civile Ospedale G. da Saliceto
city: Reggio Calabria
country: Italy
facility: Div. Ematologia AO Bianchi Melacrino Morelli
city: Reggio Emilia
country: Italy
facility: Ematologia, Azienda Ospedaliera Arcispedale "S.Maria Nuova"
city: Roma
country: Italy
facility: Ematologia, Università "La Sapienza"
city: Siena
country: Italy
facility: Clinica Ematologia Policlino Le Scotte
city: Terni
country: Italy
facility: Struttura Complessa di Onco-Ematologia Azienda Ospedaliera S.Maria
city: Torino
country: Italy
facility: SC Ematologia - Città della Salute e della Scienza
city: Torino
country: Italy
facility: SC Ematologia U - Città della Salute e della Scienza
city: Udine
country: Italy
facility: Clinica Ematologica e Unità di Terapie Cellulari 'Carlo Melzi' AOU S. Maria della Misericordia
Study officials:
affiliation: UOC Ematologia 1/CTMO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
name: Luca Baldini, Prof.
role: PRINCIPAL_INVESTIGATOR
References: