Clinical trial NCT00930514: A Pharmacokinetic Study of Subcutaneous and Intravenous Rituximab in Participants With Follicular Lymphoma
Official title: A Two Stage Phase Ib Study to Investigate the Pharmacokinetics, Safety and Tolerability of Rituximab Subcutaneous (SC) Formulation in Patients With Follicular Lymphoma (FL) as Part of Maintenance Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, Follicular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-06-30
Enrollment: 281
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2 stage study will compare the pharmacokinetics and safety profile of subcutaneous and intravenous rituximab in participants with follicular lymphoma. In the first stage, participants who have achieved at least a partial response after induction treatment with intravenous rituximab will be randomized to one of 3 treatment cohorts, to receive rituximab 375 milligram per square meter (mg/m\^2) intravenously, 375 mg/m\^2 subcutaneously or 625 mg/m\^2 subcutaneously, and pharmacokinetics evaluated on an ongoing basis. Upon selection of the subcutaneous dose (800 mg/m\^2) which results in rituximab trough plasma concentration (C trough) values comparable to those achieved with the intravenous formulation, participants in the second stage of the study will be randomized to receive either the subcutaneous or intravenous formulation to demonstrate comparability of the C trough levels with both routes of administration. Maintenance therapy will continue every 2 or 3 months with the subcutaneous formulation.


Eligibility criteria: Inclusion Criteria:

* CD20-positive follicular non-Hodgkin's lymphoma (NHL)
* Documented partial or complete response a the end of induction treatment with rituximab
* Must have completed induction treatment, and received at least 1 dose of intravenous rituximab maintenance treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of less than and equal to (\<=) 2
* Life expectancy of greater than and equal to (\>=) 6 months

Exclusion Criteria:

* Histological evidence of transformation of NHL, or types of NHL other than follicular lymphoma
* Presence or history of central nervous system disease
* History of malignancy other than follicular NHL
* Recent major surgery (within 4 weeks prior to screening), excluding lymph node biopsy

Primary outcomes:
measure: Minimum Observed Plasma Trough Concentration (C trough)
timeFrame: Up to 29 months
Secondary outcomes:
measure: Area Under the Curve From Time Zero to end of Dosing Interval (AUCtau)
timeFrame: Up to 29 months
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Up to 29 months
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Up to 29 months
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Up to 29 months
measure: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Up to 29 months
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Córdoba
country: Argentina
city: Rosario
country: Argentina
city: Kogarah
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Kurralta Park
country: Australia
state: South Australia
city: Fitzroy
country: Australia
state: Victoria
city: Porto Alegre
country: Brazil
state: RS
city: Barretos
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Calgary
country: Canada
state: Alberta
city: St. John's
country: Canada
state: Newfoundland and Labrador
city: Halifax
country: Canada
state: Nova Scotia
city: Montreal
country: Canada
state: Quebec
city: Quebec
country: Canada
city: Brno
country: Czech Republic
city: Hradec Kralove
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Herlev
country: Denmark
city: Guayaquil
country: Ecuador
city: Quito
country: Ecuador
city: Helsinki
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Marseille
country: France
city: Montpellier
country: France
city: Reims
country: France
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petach Tikva
country: Israel
city: Ramat Gan
country: Israel
city: Bergamo
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Pisa
country: Italy
state: Toscana
city: Seoul
country: Korea, Republic of
city: Aguascalientes
country: Mexico
city: Mexico City, Distrito Federal
country: Mexico
city: Monterrey
country: Mexico
city: Oslo
country: Norway
city: Lima
country: Peru
city: Lima
country: Peru
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Moscow
country: Russian Federation
city: Bratislava
country: Slovakia
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Huddinge
country: Sweden
city: Sundsvall
country: Sweden
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Basel
country: Switzerland
city: Cambridge
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Nottingham
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Salar A, Avivi I, Bittner B, Bouabdallah R, Brewster M, Catalani O, Follows G, Haynes A, Hourcade-Potelleret F, Janikova A, Larouche JF, McIntyre C, Pedersen M, Pereira J, Sayyed P, Shpilberg O, Tumyan G. Comparison of subcutaneous versus intravenous administration of rituximab as maintenance treatment for follicular lymphoma: results from a two-stage, phase IB study. J Clin Oncol. 2014 Jun 10;32(17):1782-91. doi: 10.1200/JCO.2013.52.2631. Epub 2014 May 12.
citation: Mao CP, Brovarney MR, Dabbagh K, Birnbock HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533. eCollection 2013.