A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma

Non-Hodgkin's Lymphoma Clinical Trial

— IIL INFL09  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01929265
• Other study ID #: IIL INFL09
• Status: Completed
• Phase: Phase 2
• First received: August 22, 2013
• Last updated: October 12, 2017
• Start date: January 2011
• Est. completion date: May 2015

Study information

• Verified date: March 2017
• Source: Fondazione Italiana Linfomi ONLUS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: May 2015
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Indolent Non-follicular
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Italiana Linfomi ONLUS

Country where clinical trial is conducted

Italy, 

Outcome

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