Clinical trial NCT01889069: A Study to Evaluate Safety, Efficacy and Pharmacokinetics of Rituximab (MabThera/Rituxan) in Participants With Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL)
Official title: A Single Arm, Multicentre, Phase IIIB Study to Evaluate Safety, Efficacy and Pharmacokinetic (PK) of Subcutaneous (SC) Rituximab Administered During Induction Phase or Maintenance in Previously Untreated Patients With CD20+ Diffuse Large B Cell Lymphoma (DLBCL) or Follicular Lymphoma (FL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-06-28
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single arm, multicenter study will evaluate the safety, efficacy and pharmacokinetic (PK) of subcutaneous (SC) rituximab in previously untreated participants with cluster of differentiation 20 positive (CD20+) DLBCL or FL. In addition to standard chemotherapy, participants will receive at least 4 doses of rituximab 1400 mg SC once a month during the Induction period, and at least 6 doses of rituximab 1400 mg SC once every two months during the Maintenance period.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed, CD20+ DLBCL or CD20+ follicular non-Hodgkin's lymphoma (NHL) Grade 1, 2 or 3a, according to the World Health Organization (WHO) classification system
* Currently being treated with rituximab intravenously (IV) in the Induction or Maintenance period, having received at least one full dose of rituximab IV, defined as standard full dose of rituximab IV 375 milligrams per square-meter (mg/m\^2) administered without interruption or early discontinuation (i.e. tolerability issues)
* Expectation and current ability for the participant to receive at least 4 additional cycles of treatment during the Induction period or 6 additional cycles of treatment during the Maintenance period (participants with follicular NHL)
* An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion greater than or equal to (\>=) 7.5 centimeters (cm), or Follicular Lymphoma International Prognostic Index (FLIPI) (low, intermediate or high risk) assessed before the first rituximab IV administration in Induction period
* At least one bi-dimensionally measurable lesion defined as \>=1.5 cm in its largest dimension on computed tomography (CT) scan
* Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 3

Exclusion Criteria:

* Transformed lymphoma or FL IIIB
* Primary central nervous system lymphoma, histologic evidence of transformation to a Burkitt lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, or primary cutaneous DLBCL
* History of other malignancy
* Ongoing corticosteroid use greater than (\>) 30 milligrams per day (mg/day) of prednisone or equivalent
* Inadequate renal, hematologic, or hepatic function
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
* Contraindications to any of the individual components of standard chemotherapy
* Other serious underlying medical conditions, which, in the Investigator's judgement, could impair the ability of the participant to participate in the study
* Recent major surgery (within 4 weeks prior to dosing, other than for diagnosis)
* Active hepatitis B virus (HBV), active hepatitis C virus (HCV) infection, or human immunodeficiency virus (HIV) infection

Primary outcomes:
measure: Percentage of Participants With Administration-Associated Reactions (AAR)
timeFrame: Baseline up to 54 months
Secondary outcomes:
measure: Percentage of Participants With At Least One Grade ≥ 3 Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to 54 months
measure: Percentage of Participants With At Least One Grade ≥ 3 Infusion/ Injection Related Reactions (IIRRs)
timeFrame: Baseline up to 54 months
measure: Percentage of Participants With At Least One Treatment-Emergent Serious Adverse Events
timeFrame: Baseline up to 54 months
measure: Percentage of Participants With Event-Free Survival (EFS) According to IWG Response Criteria
timeFrame: Day 1 up to first occurrence of progression or relapse, or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first (up to maximum 54 months)
measure: Percentage of Participants With Progression-Free Survival (PFS) According to IWG Response Criteria
timeFrame: Day 1 up to first occurrence of progression or relapse, or death, whichever occurs first (up to maximum 54 months)
measure: Percentage of Participants With Overall Survival (OS)
timeFrame: Day 1 until death (up to maximum 54 months)
measure: Percentage of Participants With Disease-Free Survival (DFS) According to IWG Response Criteria
timeFrame: From 4 to 8 weeks after end of Induction period up to relapse or death from any cause, whichever occurs first (up to maximum 54 months) (end of Induction period = up to 8 months)
measure: Percentage of Participants With Complete Response (CR) According to IWG Response Criteria
timeFrame: At 4 to 8 weeks after end of Induction period (end of Induction period = up to 8 months)
measure: FL: Plasma Trough Concentrations of Rituximab
timeFrame: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
measure: FL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
timeFrame: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
measure: FL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
timeFrame: Induction collection: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, and Cycle 8 Predose on Day 1
measure: DLBCL: Plasma Concentrations of Rituximab
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
measure: DLBCL: Plasma Trough Concentrations of Rituximab
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 pre-dose on Day 1
measure: DLBCL: Area Under the Plasma Concentration-Time Curve (AUC) of Rituximab
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
measure: DLBCL: Maximum Plasma Concentration (Cmax) of Rituximab
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
measure: DLBCL: Apparent Total Clearance (CL/F) of Rituximab
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
measure: DLBCL: Plasma Trough Concentrations of Rituximab in Participants With Complete Response/Complete Response Unconfirmed (CR/CRu)
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
measure: DLBCL: Overall Geometric Least Square (LS) Mean Plasma Trough Concentrations of Rituximab
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
measure: DLBCL: Plasma Concentrations During Different Scheduling of Rituximab SC R-CHOP-14 or R-CHOP-21
timeFrame: Cycle 2 Predose, Cycle 3 Predose, Cycle 4 Predose, Cycle 5 Predose, Baseline Predose, Cycle 7 Predose on Day 1, Cycle 7 Day 7, Cycle 7 Day 14, Cycle 8 Predose on Day 1
measure: Rituximab Administration Satisfaction Questionnaire (RASQ) Convenience and Satisfaction Domain Scores
timeFrame: DLBCL: Cycle (C) 2, C3, C4, C5, C6, End of C8; FL: Induction: C3, C4, C5, C6, C8, Maintenance: C2, C3, C4, C5, C6, C7, C8, C10, C12, End of treatment (4-8 weeks after last dose)
Other outcomes:
Locations:
city: Rionero in Vulture
country: Italy
facility: Irccs Crob
state: Basilicata
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi-Melacrino-Morelli; Unità Operativa di Ematologia
state: Calabria
city: Avellino
country: Italy
facility: Azienda Ospedaliera S.G. Moscati; Divisione Ematologia
state: Campania
city: Aversa
country: Italy
facility: Asl ce - p.o. Avers; Uoc ematologia
state: Campania
city: Caserta
country: Italy
facility: A.O. San Sebastiano; U.O.C. Oncologia
state: Campania
city: Napoli
country: Italy
facility: Seconda università degli studi di napoli; Medicina clinica e sperimentale magrassi - lanzara
state: Campania
city: Latina
country: Italy
facility: Osp. Santa Maria Goretti; Ematologia
state: Lazio
city: Roma
country: Italy
facility: Ospedale S. Eugenio; Divisione Di Ematologia
state: Lazio
city: Roma
country: Italy
facility: Regina Elena National Cancer Institute; Hematology
state: Lazio
city: Roma
country: Italy
facility: Az. Osp. S. Camillo Forlanini; Uo Ematologia E Trapianti Di Midollo Osseo
state: Lazio
city: Roma
country: Italy
facility: Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Giovanni Addolorata; UOC Ematologia
state: Lazio
city: Ronciglione
country: Italy
facility: ASL Viterbo; Presidio Ospedaliero di Ronciglione; UOC Ematologia
state: Lazio
city: Como
country: Italy
facility: Ospedale Valduce;U.O.S. Oncologia Ed Ematologia
state: Lombardia
city: Crema
country: Italy
facility: ASST DI CREMA; U O Oncologia Medica
state: Lombardia
city: Lecco
country: Italy
facility: ASST DI LECCO; Oncologia Medica
state: Lombardia
city: Mantova
country: Italy
facility: Az. Osp. Carlo Poma; Divisione Di Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Osp. San Raffaele; Dip. Di Oncoematologia
state: Lombardia
city: Milano
country: Italy
facility: Ist. Nazionale Per Lo Studio E Cura Dei Tumori; Div. Ematologia Trapianto Midollo Osseo Allogenico
state: Lombardia
city: Pavia
country: Italy
facility: Irccs Policlinico San Matteo; Divisione Di Ematologia
state: Lombardia
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas;U.O. Oncologia Medica Ed Ematologia
state: Lombardia
city: Ascoli Piceno
country: Italy
facility: Ospedale Gen.Le Prov.Le 'C.G.Mazzoni'; Ematologia
state: Marche
city: Civitanova Marche
country: Italy
facility: Ospedale di Civitanova Marche; Medicina Interna
state: Marche
city: Macerata
country: Italy
facility: Ospedale di Macerata; Medicina Generale
state: Marche
city: Campobasso
country: Italy
facility: Università Cattolica Del Sacro Cuore S.S. Giovanni Paolo Ii; Uoc Di Onco-Ematologia
state: Molise
city: Alessandria
country: Italy
facility: Ospedale Civile SS. Antonio E Biagio DI Alessandria; Ematologia
state: Piemonte
city: Novara
country: Italy
facility: Univ. Piemonte Est Amedeo Avogadro; Div.Ematologia- Dip.Clinica Med.Sperim.& Ircad
state: Piemonte
city: Bari
country: Italy
facility: Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica
state: Puglia
city: Foggia
country: Italy
facility: Azienda ospedaliera oo rr di foggi; Hematology
state: Puglia
city: Cagliari
country: Italy
facility: Ospedale Roberto Binaghi; Centro trapianti di midollo osseo
state: Sardegna
city: Nuoro
country: Italy
facility: Osp. San Francesco; Ematologia e CTMO
state: Sardegna
city: Catania
country: Italy
facility: ARNAS Garibaldi; Ematologia
state: Sicilia
city: Messina
country: Italy
facility: Az. Osp. Papardo; Struttura Complessa Di Ematologia
state: Sicilia
city: Palermo
country: Italy
facility: ARNAS-Ospedale Civico Maurizio Ascoli; Unità Operativa di Oncologia Medica
state: Sicilia
city: Palermo
country: Italy
facility: Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
state: Sicilia
city: Pisa
country: Italy
facility: Ospedale Santa Chiara; Unita Operativa Di Ematologia
state: Toscana
city: Prato
country: Italy
facility: USL 4 di Prato - Nuovo Ospeale di Prato
state: Toscana
city: Terni
country: Italy
facility: A.O. Santa Maria Terni; S.C. Oncoematologia
state: Umbria
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
state: Veneto
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: