A Study of MabThera (Rituximab) in Elderly Patients With Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

A Randomized, Open-label Study of MabThera Maintenance Therapy Compared With no Further Therapy After a Brief Induction With Chemotherapy Plus MabThera on Failure-free Survival in Treatment-naïve Elderly Patients With Advanced Follicular Lymphoma

This study will evaluate the efficacy and safety of brief induction therapy with a chemotherapeutic regimen containing MabThera, followed by either maintenance therapy with MabThera or no further therapy. The anticipated time on study treatment is 1-2 years, and the target sample size is 100-500 individuals.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: rituximab [Mabthera/Rituxan]

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Abruzzo
    • Pescara, Abruzzo, Italy, 65100
      • Ospedale Civile Dello Spirito Santo; Divisione Di Ematologia
  • Calabria
    • Reggio Calabria, Calabria, Italy, 89100
      • Ospedale Riuniti; Divisione Di Ematologia
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica
    • Napoli, Campania, Italy, 80131
      • Ospedale Cardarelli; Divisione Di Ematologia
    • Napoli, Campania, Italy, 80131
      • Nuovo Policlinico, Ii Facolta; Divisione Di Ematologia
    • Nocera Inferiore, Campania, Italy, 84014
      • Presidio Ospedaliero Umberto I; U.O. Di Medicina Interna Ed Oncoematologia
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O. Universitaria Policlinico Di Modena; Ematologia
    • Modena, Emilia-Romagna, Italy, 41100
      • A.O. Universitaria Policlinico Di Modena; Radiologia
    • Piacenza, Emilia-Romagna, Italy, 29100
      • Az. Osp. Ospedale Civile; U.O. Di Oncologia Medica Ed Ematologia
    • Ravenna, Emilia-Romagna, Italy, 48100
      • Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
      • Az. Osp. Arcispedale S. Maria Nuova; U.O. Di Ematologia
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • Policlinico Universitario; Clinica Oncologia - Padiglione Pennato
  • Lazio
    • Roma, Lazio, Italy, 00161
      • Universita' Degli Studi La Sapienza-Ist.Di Ematologia;Dip. Biotecnologie Cel CELLULARI ED EMATOLOGIA
    • Roma, Lazio, Italy, 00144
      • Ospedale S. Eugenio; Divisione Di Ematologia
    • Roma, Lazio, Italy, 00168
      • Uni Cattolica; Divisione Di Ematologia
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • ASST PAPA GIOVANNI XXIII; Ematologia
    • Brescia, Lombardia, Italy, 25123
      • A.O. Spedali Civili Di Brescia-P.O. Spedali Civili;U.O. Ematologia
    • Cremona, Lombardia, Italy, 26100
      • ASST DI CREMONA; U.O.S. di Ematologia
    • Milano, Lombardia, Italy, 20122
      • Ospedale Maggiore Di Milano; U.O. Ematologia I - Padiglione Marcora
    • Milano, Lombardia, Italy, 20162
      • Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
    • Milano, Lombardia, Italy, 20133
      • Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico
    • Monza, Lombardia, Italy, 20052
      • ASST DI MONZA; Ematologia
  • Marche
    • Ancona, Marche, Italy, 60020
      • Ospedale Regionale Di Torrette; Clinica Di Ematologia
    • Pesaro, Marche, Italy, 61100
      • Ospedale Civile; S.C. Ematologia
  • Piemonte
    • Alessandria, Piemonte, Italy, 15121
      • Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
    • Biella, Piemonte, Italy, 13051
      • Az. Osp. Di Biella; Divisione Di Ematologia
    • Candiolo, Piemonte, Italy, 10060
      • Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
    • Cuneo, Piemonte, Italy, 12100
      • Az. Osp. S. Croce Ospedale Generale; Sezione Di Ematologia
    • Orbassano, Piemonte, Italy, 10043
      • Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico
    • Torino, Piemonte, Italy, 10126
      • A.O. Universitaria S. Giovanni Battista-Molinette Di Torino; Ematologia 1
    • Torino, Piemonte, Italy, 10126
      • A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia
  • Puglia
    • Bari, Puglia, Italy, 70124
      • Uni Degli Studi Di Bari, Policlinico; Cattedra Di Ematologia,Dipart. Di Medicina Interna E Publica
    • San Giovanni Rotondo, Puglia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo Della Sofferenza; Ematologia E Trapianto Di Midollo Osseo
  • Sardegna
    • Cagliari, Sardegna, Italy, 09121
      • Ospedale Oncologico A Businco-Cagliari; Ematologia Sez.
  • Sicilia
    • Messina, Sicilia, Italy, 98165
      • Az. Osp. Papardo; Struttura Complessa Di Ematologia
    • Palermo, Sicilia, Italy, 90146
      • Ospedale V. Cervello; U.O. Ematologia E Trapianti
    • Via S. Sofia 78, Sicilia, Italy, 95123
      • Ospedale Ferrarotto; Divisione Di Ematologia
  • Toscana
    • Firenze, Toscana, Italy, 50135
      • Az. Osp. Di Careggi; Divisione Di Ematologia
    • Pisa, Toscana, Italy, 56100
      • Ospedale Santa Chiara; Unita Operativa Di Ematologia
  • Trentino-Alto Adige
    • Bolzano, Trentino-Alto Adige, Italy, 39100
      • Azienda Sanitaria Di Bolzano; Ematologia E Centro Trapianto Mid.Osseo
  • Umbria
    • Perugia, Umbria, Italy, 06126
      • Dept. Medicina Clinica E Sperimentale; Sez. Medicina Interna E Scienze Oncologiche - Pol. Monteluce
  • Veneto
    • Venezia, Veneto, Italy, 30122
      • Ospedale Civile Ss. Giovanni E Paolo; Ematologia
    • Verona, Veneto, Italy, 37130
      • Uni Di Verona Policlinico G.B. Rossi; Divisione E Cattedra Di Ematologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients 60-75 years of age;
• B-cell follicular NHL;
• no previous treatment;
• active disease, with rapid progression.

Exclusion Criteria:

• other cancer within 3 years of study, except carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ of the breast treated with lumpectomy;
• long-term use (>1 month) of systemic corticosteroids;
• central nervous system involvement;
• history of significant cardiovascular disease;
• positive test result for HIV, or hepatitis B or C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: rituximab [Mabthera/Rituxan]; Intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Disease Progression or Death	PFS from randomization was measured from the date of randomization to the date of documented disease progression, relapse, or death from any cause. PFS function was estimated using Kaplan-Meier product-limit method. Responding participants and participants who were lost to follow up were censored at their last assessment date.	12, 24, and 34 months
PFS Randomization- Percentage of Participants Estimated to be Free of Progression at 12, 24, and 34 Months	PFS from randomization was measured from the date of randomization to the date of documented disease progression, relapse, or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last assessment date. PFS was estimated using Kaplan-Meier methods.	12, 24, and 34 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Estimated to be Free of Progression at 12, 24, and 36 Months	PFS from enrollment was measured from the date of enrollment to the date of disease progression, relapse, or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last assessment date. Estimates of PFS function were made with the Kaplan-Meier product-limit method.	12, 24, and 36 months
Disease-Free Survival (DFS) From Randomization - Percentage of Participants Disease Free at 12, 24, and 36 Months	DFS was defined for all participants who achieved a complete response (CR) or unconfirmed CR (CRu) at Month 3 or later, after the completion of induction phase and was measured from the time of randomization to the date of relapse or death as a result of lymphoma or acute toxicity of treatment. Participants without relapse were censored at their last assessment date. Estimates of DFS were made using Kaplan-Meier product-limit method.	12, 24, and 36 months
Overall Survival (OS) From Randomization - Percentage of Participants Estimated to be Alive at 12, 24, and 34 Months	OS from randomization was defined as the date of randomization to the date of death from any cause. Participants still alive at the time of the final analysis were censored at the date of the last contact. Estimates of the OS function were made by the Kaplan-Meier product-limit method.	12, 24, and 34 months
Overall Survival (OS) From Randomization - Percentage of Participants With Death	OS from randomization was defined as the date of randomization to the date of death from any cause. Participants still alive at the time of the final analysis were censored at the date of the last contact. Estimates of the OS function were made by the Kaplan-Meier product-limit method.	12, 24, and 34 months
OS From Enrollment - Percentage of Participants Estimated to be Alive at 12, 24, and 36 Months	OS from enrollment was defined as the date of enrollment to the date of death from any cause. Participants still alive at the time of the final analysis were censored at the date of the last contact. Estimates of the OS function were made by the Kaplan-Meier product-limit method.	12, 24, and 36 months
Percentage of Participants With a Response During the Induction Phase	Participants without a response assessment (due to any reasons) were considered as non-responders.	Months 1 to 8
Percentage of Participants With a Molecular Response in the Induction Phase	Molecular responders were defined as the proportion of CR/CRu participants with a positive bcl-2/IgH (non-Hodgkin's Lymphoma [NHL] marker) at baseline, whose laboratory values were undetectable after treatment.	Months 5 and 8
Duration of Response Using a Traditional Approach - Percentage of Participants Estimated to Have a Sustained Response at 12, 24, and 34 Months	Duration of response (DOR) was defined for all participants who achieved a response (CR, CRu, and PR) at Month 3 or later, after the completion of induction phase and was measured from the date of randomization until the date of progression, relapse, or death as a result of follicular lymphoma (FL). Participants without relapse, progression, or death for causes other than FL were censored at their last assessment date. Analyses on this endpoint were performed with two different approaches. For the traditional approach, duration of response was estimated as the proportion of participants alive without progression or relapse of disease with the Kaplan-Meier method.	Months 12, 24, and 34
Duration of Response Using the Competing Risk Approach - Cumulative Percentage of Participants With Progression, Relapse or Death as a Result of FL at 12, 24, and 34 Months	DOR was defined for all participants who achieved a response (CR, CRu, and PR) at Month 3 or later, after the completion of induction phase and was measured from the date of randomization until the date of progression, relapse, or death as a result of FL. Participants without relapse, progression, or death for causes other than FL were censored at their last assessment date. Analyses on this endpoint were performed with two different approaches. For the competing risk approach, deaths for causes other than FL were considered as competing events. DOR was estimated with the cumulative incidence of progression, relapse, or death as a result of FL.	Months 12, 24, and 34

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Ladetto M, Lobetti-Bodoni C, Mantoan B, Ceccarelli M, Boccomini C, Genuardi E, Chiappella A, Baldini L, Rossi G, Pulsoni A, Di Raimondo F, Rigacci L, Pinto A, Galimberti S, Bari A, Rota-Scalabrini D, Ferrari A, Zaja F, Gallamini A, Specchia G, Musto P, Rossi FG, Gamba E, Evangelista A, Vitolo U; Fondazione Italiana Linfomi. Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program. Blood. 2013 Nov 28;122(23):3759-66. doi: 10.1182/blood-2013-06-507319. Epub 2013 Oct 1.
• Vitolo U, Ladetto M, Boccomini C, Baldini L, De Angelis F, Tucci A, Botto B, Chiappella A, Chiarenza A, Pinto A, De Renzo A, Zaja F, Castellino C, Bari A, Alvarez De Celis I, Evangelista A, Parvis G, Gamba E, Lobetti-Bodoni C, Ciccone G, Rossi G. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013 Sep 20;31(27):3351-9. doi: 10.1200/JCO.2012.44.8290. Epub 2013 Aug 19.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2004
• Primary Completion (Actual): July 21, 2011
• Study Completion (Actual): July 21, 2011

Study Registration Dates

• First Submitted: June 11, 2010
• First Submitted That Met QC Criteria: June 14, 2010
• First Posted (Estimate): June 15, 2010

Study Record Updates

• Last Update Posted (Actual): August 15, 2017
• Last Update Submitted That Met QC Criteria: July 6, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: ML17638