Clinical trial NCT01724021: A Study of Participant Preference With Subcutaneous Versus Intravenous MabThera/Rituxan in Participants With CD20+ Diffuse Large B-Cell Lymphoma or CD20+ Follicular Non-Hodgkin's Lymphoma Grades 1, 2 or 3a
Official title: A Randomized, Open-label, Mutli-centre Study to Evaluate Patient Preference With Subcutaneous Administration of Rituximab Versus Intravenous Rituximab in Previously Untreated Patients With CD20+ Diffuse Large B-cell Lymphoma or CD20+ Follicular Non-Hodgkin's Lymphoma Grades 1, 2, OR 3A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diffuse Large B-Cell Lymphoma, Non-Hodgkin's Lymphoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-11-09
Enrollment: 743
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multi-center, open-label, randomized study will evaluate the participant preference with subcutaneous versus intravenous administration of MabThera/Rituxan (rituximab) in participants with CD20+ diffuse large B-cell lymphoma or CD20+ follicular non-Hodgkin's lymphoma. In Arm A, participants will receive MabThera/Rituxan 375 mg/m2 intravenously (IV) on Day 1 of Cycle 1 and MabThera/Rituxan 1400 mg subcutaneously (SC) on Day 1 of Cycles 2-4, followed by MabThera/Rituxan IV in Cycles 5-8. Participants in Arm B will receive MabThera/Rituxan IV in Cycles 1-4 and SC in Cycles 5-8. All participants will receive 6-8 cycles of standard chemotherapy (according to local country practice) with 8 cycles of MabThera/Rituxan. Anticipated time on study treatment is up to 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Adult participants , \>/= 18 and \</= 80 years of age
* Histologically confirmed, previously untreated CD20+ diffuse large B-cell lymphoma (DLBCL) or CD20+ follicular non-Hodgkin's lymphoma (NHL) Grade 1, 2, or 3a, according to World Health Organization (WHO) classification
* An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion \>/= 7.5 cm, or Follicular Lymphoma International Prognostic Index (FLIPI; low, intermediate or high risk)
* At least one bi-dimensionally measurable lesion defined as \>/=1.5 cm in its largest dimension on CT scan
* Eastern Cooperative Oncology Group (ECOG) performance status \</= 3

Exclusion Criteria:

* Transformed lymphoma or follicular lymphoma IIIB
* Primary central nervous system (CNS) lymphoma, histologic evidence of transformation to Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, primary cutaneous DLBCL, or primary DLBCL of the testis
* History of other malignancy that could affect compliance with the protocol or interpretation of the results; this includes a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission for \>/= 5 years prior to enrolment; participants with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible
* Prior therapy for DLBCL or NHL, with the exception of nodal biopsy or local irradiation
* Prior treatment with cytotoxic drugs (with the exclusion of intrathecal methotrexate for CNS prophylaxis in DLBCL) or rituximab for another condition, or prior use of an anti-CD20 drug
* Prior use of monoclonal antibody within 3 months prior to randomization
* Chemotherapy or other investigational therapy within 28 days prior to randomization
* Ongoing corticosteroid use \> 30 mg/day prednisolone or equivalent
* Inadequate renal. hematologic or hepatic function
* Active and/or severe infection or any major episode of infection within 4 weeks prior to randomization
* Active hepatitis B virus or active hepatitis C virus infection
* History of human immunodeficiency (HIV) seropositive status
* A positive pregnancy test in women of childbearing potential
* Life expectancy of less than 6 months

Primary outcomes:
measure: Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 6
timeFrame: Cycle 6 (Up to 24 weeks)
measure: Percentage of Participants Indicating a Preference for Rituximab Subcutaneous (SC) Over Rituximab Intravenously (IV) at Cycle 8
timeFrame: Cycle 8 (Up to 32 weeks)
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (AEs)
timeFrame: Randomization of first participant to clinical cutoff date (Up to 4 years)
measure: Time Required for Rituximab Administration (Subcutaneous [SC] or Intravenous [IV])
timeFrame: Cycle 1-4, Cycle 5-8 for both SC and IV (Up to 32 weeks)
measure: Cancer Therapy Satisfaction Questionnaire (CTSQ) Score
timeFrame: During Cycle 4, 8 of treatment (Up to 32 weeks)
measure: Rituximab Administration Satisfaction Questionnaire (RASQ) Score
timeFrame: During Cycle 4, 8 of treatment (Up to 32 weeks)
measure: Complete Response (CR) Rate
timeFrame: 28 days (± 3 days) after Day 1 of the last dose of induction treatment
measure: Event-free Survival (EFS)
timeFrame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
measure: Disease-free Survival (DFS)
timeFrame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
measure: Progression-free Survival (PFS)
timeFrame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
measure: Overall Survival (OS)
timeFrame: From the time of randomization until disease progression or 24 months post treatment follow up or which ever occur first (Up to 4 years)
measure: Percentage of Participants With Anti-Rituximab Antibodies Over Time
timeFrame: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)
measure: Percentage of Participants With Anti-Recombinant Human Hyaluronidase (rHuPH20) Antibodies Over Time
timeFrame: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)
measure: Summary of Observed Serum Rituximab Concentration
timeFrame: Pre-dose Cycle 1 to 8, interim staging, final staging, 6, 12 months follow-up, end of study (Up to 4 years)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Corrientes
country: Argentina
city: Santa Fé
country: Argentina
city: Canberra
country: Australia
state: Australian Capital Territory
city: Camperdown
country: Australia
state: New South Wales
city: Liverpool
country: Australia
state: New South Wales
city: Randwick
country: Australia
state: New South Wales
city: Brisbane
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Hobart
country: Australia
state: Tasmania
city: Geelong
country: Australia
state: Victoria
city: Malvern
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Wodonga
country: Australia
state: Victoria
city: Nedlands
country: Australia
state: Western Australia
city: Perth
country: Australia
state: Western Australia
city: Krems
country: Austria
city: Linz
country: Austria
city: Salzburg
country: Austria
city: Steyr
country: Austria
city: Wien
country: Austria
city: Belo Horizonte
country: Brazil
state: MG
city: Juiz de Fora
country: Brazil
state: MG
city: Varginha
country: Brazil
state: MG
city: Recife
country: Brazil
state: PE
city: Curitiba
country: Brazil
state: PR
city: Londrina
country: Brazil
state: PR
city: Caxias do Sul
country: Brazil
state: RS
city: Novo Hamburgo
country: Brazil
state: RS
city: Santa Maria
country: Brazil
state: RS
city: Santo Andre
country: Brazil
state: SP
city: Sao Jose do Rio Preto
country: Brazil
state: SP
city: Burnaby
country: Canada
state: British Columbia
city: Vancouver
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: Hamilton
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Santiago
country: Chile
city: Santiago
country: Chile
city: Viña del Mar
country: Chile
city: Monteria
country: Colombia
city: Osijek
country: Croatia
city: Aalborg
country: Denmark
city: Holstebro
country: Denmark
city: Santiago de los Caballeros
country: Dominican Republic
city: Alexandria
country: Egypt
city: Cairo
country: Egypt
city: San Salvador
country: El Salvador
city: Aschaffenburg
country: Germany
city: Augsburg
country: Germany
city: Bamberg
country: Germany
city: Bayreuth
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Berlin
country: Germany
city: Bielefeld
country: Germany
city: Bielefeld
country: Germany
city: Bochum
country: Germany
city: Bochum
country: Germany
city: Bonn
country: Germany
city: Bottrop
country: Germany
city: Brandenburg
country: Germany
city: Bremen
country: Germany
city: Bremerhaven
country: Germany
city: Coesfeld
country: Germany
city: Darmstadt
country: Germany
city: Darmstadt
country: Germany
city: Dresden
country: Germany
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Eisenach
country: Germany
city: Essen
country: Germany
city: Essen
country: Germany
city: Frankfurt an der Oder
country: Germany
city: Frankfurt
country: Germany
city: Frankfurt
country: Germany
city: Frankfurt
country: Germany
city: Freiburg
country: Germany
city: Fürth
country: Germany
city: Georgsmarienhütte
country: Germany
city: Giessen
country: Germany
city: Giessen
country: Germany
city: Goslar
country: Germany
city: Gütersloh
country: Germany
city: Halle
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hamburg
country: Germany
city: Hamm
country: Germany
city: Hamm
country: Germany
city: Hanau
country: Germany
city: Hannover
country: Germany
city: Hannover
country: Germany
city: Herford
country: Germany
city: Jena
country: Germany
city: Kaiserslautern
country: Germany
city: Kassel
country: Germany
city: Köln
country: Germany
city: Leer
country: Germany
city: Leipzig
country: Germany
city: Limburg
country: Germany
city: Lübeck
country: Germany
city: Magdeburg
country: Germany
city: Mainz
country: Germany
city: Mannheim
country: Germany
city: Marburg
country: Germany
city: Mayen
country: Germany
city: Moers
country: Germany
city: Mutlangen
country: Germany
city: Mönchengladbach
country: Germany
city: Mülheim
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Neunkirchen/Saar
country: Germany
city: Nürnberg
country: Germany
city: Oldenburg
country: Germany
city: Osnabrueck
country: Germany
city: Paderborn
country: Germany
city: Pforzheim
country: Germany
city: Pinneberg
country: Germany
city: Pirna
country: Germany
city: Porta Westfalica
country: Germany
city: Pößneck
country: Germany
city: Ravensburg
country: Germany
city: Recklinghausen
country: Germany
city: Regensburg
country: Germany
city: Rostock
country: Germany
city: Rostock
country: Germany
city: Rostock
country: Germany
city: Rostock
country: Germany
city: Rötha
country: Germany
city: Schweinfurt
country: Germany
city: Schwäbisch-Hall
country: Germany
city: Siegburg
country: Germany
city: Stade
country: Germany
city: Stendal
country: Germany
city: Stuttgart
country: Germany
city: Traunstein
country: Germany
city: Trier
country: Germany
city: Velbert
country: Germany
city: Villingen-Schwenningen
country: Germany
city: Weilheim
country: Germany
city: Wiesbaden
country: Germany
city: Wilhelmshaven
country: Germany
city: Witten
country: Germany
city: Wuerselen
country: Germany
city: Zittau
country: Germany
city: Zwickau
country: Germany
city: Guatemala
country: Guatemala
city: Guatemala
country: Guatemala
city: Hong Kong
country: Hong Kong
city: Hong Kong
country: Hong Kong
city: Budapest
country: Hungary
city: Gyor
country: Hungary
city: Gyula
country: Hungary
city: Kaposvar
country: Hungary
city: Nyíregyháza
country: Hungary
city: Szeged
country: Hungary
city: Szolnok
country: Hungary
city: Bandung
country: Indonesia
city: Jakarta
country: Indonesia
city: Jogjakarta
country: Indonesia
city: Surabaya
country: Indonesia
city: Catanzaro
country: Italy
state: Calabria
city: Ferrara
country: Italy
state: Emilia-Romagna
city: Parma
country: Italy
state: Emilia-Romagna
city: Piacenza
country: Italy
state: Emilia-Romagna
city: Roma
country: Italy
state: Lazio
city: Candiolo
country: Italy
state: Piemonte
city: Cuneo
country: Italy
state: Piemonte
city: Brindisi
country: Italy
state: Puglia
city: Lecce
country: Italy
state: Puglia
city: Palermo
country: Italy
state: Sicilia
city: Lido Di Camaiore
country: Italy
state: Toscana
city: Livorno
country: Italy
state: Toscana
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Ampang
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Kuching
country: Malaysia
city: Sabah
country: Malaysia
city: Amstelveen
country: Netherlands
city: Amsterdam
country: Netherlands
city: Apeldoorn
country: Netherlands
city: Beverwijk
country: Netherlands
city: Capelle Aan De Yssel
country: Netherlands
city: Delftzijl
country: Netherlands
city: Den Haag
country: Netherlands
city: Den Haag
country: Netherlands
city: Eindhoven
country: Netherlands
city: Goes
country: Netherlands
city: Leidschendam
country: Netherlands
city: Rotterdam
country: Netherlands
city: Tilburg
country: Netherlands
city: Utrecht
country: Netherlands
city: Auckland
country: New Zealand
city: Panama City
country: Panama
city: Panama
country: Panama
city: Panama
country: Panama
city: Arequipa
country: Peru
city: Cusco
country: Peru
city: La Victoria, Lima
country: Peru
city: Cebu City
country: Philippines
city: Manila
country: Philippines
city: Manila
country: Philippines
city: Quezon City
country: Philippines
city: Lisboa
country: Portugal
city: Matosinhos
country: Portugal
city: Ponta Delgada
country: Portugal
city: Setubal
country: Portugal
city: Viseu
country: Portugal
city: Baia Mare
country: Romania
city: Brasov
country: Romania
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Craiova
country: Romania
city: Iasi
country: Romania
city: Sibiu
country: Romania
city: Timisoara
country: Romania
city: Falun
country: Sweden
city: Göteborg
country: Sweden
city: Jönköping
country: Sweden
city: Karlstad
country: Sweden
city: Sundsvall
country: Sweden
city: Västerås
country: Sweden
city: Kaohsung
country: Taiwan
city: Taichung
country: Taiwan
city: Taipei
country: Taiwan
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Khon Kaen
country: Thailand
city: Ankara
country: Turkey
city: Ankara
country: Turkey
city: Denizli
country: Turkey
city: Erzurum
country: Turkey
city: Malatya
country: Turkey
city: Ha Noi
country: Vietnam
city: Hochiminh city
country: Vietnam
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Rummel M, Kim TM, Aversa F, Brugger W, Capochiani E, Plenteda C, Re F, Trask P, Osborne S, Smith R, Grigg A. Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20+ diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab). Ann Oncol. 2017 Apr 1;28(4):836-842. doi: 10.1093/annonc/mdw685.
citation: Theodore-Oklota C, Humphrey L, Wiesner C, Schnetzler G, Hudgens S, Campbell A. Validation of a treatment satisfaction questionnaire in non-Hodgkin lymphoma: assessing the change from intravenous to subcutaneous administration of rituximab. Patient Prefer Adherence. 2016 Sep 13;10:1767-1776. doi: 10.2147/PPA.S108489. eCollection 2016.