A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma (IIL INFL09)

A Phase II Study of Bendamustine in Combination With Rituximab as Initial Treatment for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma

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).

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma; Indolent Non-follicular
• Intervention / Treatment: Drug: Bendamustine

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.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy
    • UOC Ematologia 1/CTMO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Napoli, Italy
    • Oncoematologia Istituto Pascale
  • Novara, Italy
    • S.C.D.U Ematologia Azienda Ospedaliero Universitaria Maggiore
  • Pavia, Italy
    • UO Ematologia Università - Policlinico San Matteo
  • Pescara, Italy
    • Ematologia Ospedale Santo Spirito
  • Piacenza, Italy
    • UOA Ematologia, Ospedale Civile Ospedale G. da Saliceto
  • Reggio Calabria, Italy
    • Div. Ematologia AO Bianchi Melacrino Morelli
  • Reggio Emilia, Italy
    • Ematologia, Azienda Ospedaliera Arcispedale "S.Maria Nuova"
  • Roma, Italy
    • Ematologia, Università "La Sapienza"
  • Siena, Italy
    • Clinica Ematologia Policlino Le Scotte
  • Terni, Italy
    • Struttura Complessa di Onco-Ematologia Azienda Ospedaliera S.Maria
  • Torino, Italy
    • SC Ematologia - Città della Salute e della Scienza
  • Torino, Italy
    • SC Ematologia U - Città della Salute e della Scienza
  • Udine, Italy
    • Clinica Ematologica e Unità di Terapie Cellulari 'Carlo Melzi' AOU S. Maria della Misericordia
  • AL
    • Alessandria, AL, Italy, 15121
      • SC Ematologia - AO SS. Antonio e Biagio e C. Arrigo
  • BS
    • Brescia, BS, Italy
      • SC Ematologia Spedali Civili
  • BZ
    • Bolzano, BZ, Italy
      • Divisione di Ematologia e Trapianti, Ospedale San Maurizio
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy
      • Divisione di Ematologia, Centro Trapianto di Cellule Staminali
  • GE
    • Genova, GE, Italy
      • Divisione Ematologia I , Ospedale San Martino
  • ME
    • Messina, ME, Italy
      • S.C. Ematologia Azienda Ospedaliera Papardo
  • MI
    • Milano, MI, Italy
      • Divisione di Ematologia Ospedale Niguarda
  • MO
    • Modena, MO, Italy
      • Centro Oncologico Modenese
  • Milano
    • Rozzano, Milano, Italy
      • Divisione di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas
  • PA
    • Palermo, PA, Italy
      • Ematologia Azienda Ospedaliero Universitaria Paolo Giaccone
  • PN
    • Aviano, PN, Italy
      • Div. Oncologia Medica - CRO, Centro di Riferimento Oncologico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Rituximab - Bendamustine (RB); 1 arm: Rituximab - Bendamustine (RB) 1 arm for all patients

Drug: Bendamustine; 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; Other Names: RIBOMUSTIN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate (CR)	Evaluated at the end of treatment	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety analysis	Evaluated during and at the end of treatment. Percentage of patients with adverse, hematological and non-hematological toxic events	5 months
Overall response rate (ORR)	Evaluated at the end of treatment. Complete plus partial remission.	5 months
Overall survival (OS)	Dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method.	at 2 years
Progression free survival (PFS)	Progression, relapse or dead for any causes after diagnosis. Evaluated by means of Kaplan-Meier method.	at 2 years
Disease free survival (PFS)	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.	at 2 years

Collaborators and Investigators

• Sponsor: Fondazione Italiana Linfomi ONLUS
• Investigators: Principal Investigator: Luca Baldini, Prof., UOC Ematologia 1/CTMO, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): March 1, 2012
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: August 22, 2013
• First Submitted That Met QC Criteria: August 22, 2013
• First Posted (Estimate): August 27, 2013

Study Record Updates

• Last Update Posted (Actual): October 13, 2017
• Last Update Submitted That Met QC Criteria: October 12, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: INFL; Indolent non-follicular; untreated INFL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Bendamustine Hydrochloride
• Other Study ID Numbers: IIL INFL09