A Pharmacokinetic Study of Subcutaneous and Intravenous Rituximab in Participants With Follicular Lymphoma

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma, Follicular
• Intervention / Treatment: Drug: Rituximab; Drug: Rituximab; Drug: Rituximab; Drug: Rituximab; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
  • Buenos Aires, Argentina, C1114AAN
  • Buenos Aires, Argentina, C1221ADC
  • Córdoba, Argentina, 5000
  • Rosario, Argentina, 2000
• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
    • Sydney, New South Wales, Australia, 2139
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 91350-200
  • SP
    • Barretos, SP, Brazil, 14784-400
    • Sao Paulo, SP, Brazil, 05403-000
    • Sao Paulo, SP, Brazil, 05652-000
• Canada
  • Quebec, Canada, G1J 1Z4
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
• Czech Republic
  • Brno, Czech Republic, 625 00
  • Hradec Kralove, Czech Republic, 500 05
  • Praha 2, Czech Republic, 128 08
• Denmark
  • Herlev, Denmark, 2730
• Ecuador
  • Guayaquil, Ecuador, EC090114
  • Quito, Ecuador, 2569
• Finland
  • Helsinki, Finland, 00029
  • Tampere, Finland, 33520
  • Turku, Finland, 20520
• France
  • Marseille, France, 13273
  • Montpellier, France, 34295
  • Reims, France, 51092
• Israel
  • Haifa, Israel, 3109601
  • Jerusalem, Israel, 9112001
  • Petach Tikva, Israel, 49100
  • Ramat Gan, Israel, 52662
• Italy
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
    • Milano, Lombardia, Italy, 20162
  • Piemonte
    • Torino, Piemonte, Italy, 10126
  • Toscana
    • Pisa, Toscana, Italy, 56100
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
• Mexico
  • Aguascalientes, Mexico, 20127
  • Mexico City, Distrito Federal, Mexico, 14050
  • Monterrey, Mexico, 64460
• Norway
  • Oslo, Norway, 0379
• Peru
  • Lima, Peru, 34
  • Lima, Peru, 11
• Poland
  • Warszawa, Poland, 02 776
  • Wroclaw, Poland, 50-367
• Russian Federation
  • Moscow, Russian Federation, 115478
• Slovakia
  • Bratislava, Slovakia, 833 10
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08003
  • Salamanca, Spain, 37007
  • Sevilla, Spain, 41013
• Sweden
  • Huddinge, Sweden, 14186
  • Sundsvall, Sweden, 85186
  • Umea, Sweden, 90185
  • Uppsala, Sweden, 75185
• Switzerland
  • Basel, Switzerland, 4031
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
  • London, United Kingdom, EC1A 7BE
  • Manchester, United Kingdom, M20 4QL
  • Nottingham, United Kingdom, NG5 1PB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rituximab IV 375 mg/m^2 (Stage 1: Cohort A)	Drug: Rituximab; Rituximab subcutaneous injection at 1400 mg dose level, administered every 2 or 3 months.; Drug: Rituximab; Rituximab subcutaneous injection at 800 mg/m^2 dose level, administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 625 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab intravenous infusion 375 milligram per square meter (mg/m^2) administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 375 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan
Active Comparator: Rituximab IV 375 mg/m^2 (Stage 2: Cohort E)	Drug: Rituximab; Rituximab subcutaneous injection at 1400 mg dose level, administered every 2 or 3 months.; Drug: Rituximab; Rituximab subcutaneous injection at 800 mg/m^2 dose level, administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 625 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab intravenous infusion 375 milligram per square meter (mg/m^2) administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 375 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan
Experimental: Rituximab SC 1400 mg (Stage 2: Cohort F)	Drug: Rituximab; Rituximab subcutaneous injection at 1400 mg dose level, administered every 2 or 3 months.; Drug: Rituximab; Rituximab subcutaneous injection at 800 mg/m^2 dose level, administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 625 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab intravenous infusion 375 milligram per square meter (mg/m^2) administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 375 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan
Experimental: Rituximab SC 375 mg/m^2 (Stage 1: Cohort B)	Drug: Rituximab; Rituximab subcutaneous injection at 1400 mg dose level, administered every 2 or 3 months.; Drug: Rituximab; Rituximab subcutaneous injection at 800 mg/m^2 dose level, administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 625 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab intravenous infusion 375 milligram per square meter (mg/m^2) administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 375 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan
Experimental: Rituximab SC 625 mg/m^2 (Stage 1: Cohort C)	Drug: Rituximab; Rituximab subcutaneous injection at 1400 mg dose level, administered every 2 or 3 months.; Drug: Rituximab; Rituximab subcutaneous injection at 800 mg/m^2 dose level, administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 625 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab intravenous infusion 375 milligram per square meter (mg/m^2) administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 375 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan
Experimental: Rituximab SC 800 mg/m^2 (Stage 1: Cohort D)	Drug: Rituximab; Rituximab subcutaneous injection at 1400 mg dose level, administered every 2 or 3 months.; Drug: Rituximab; Rituximab subcutaneous injection at 800 mg/m^2 dose level, administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 625 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab intravenous infusion 375 milligram per square meter (mg/m^2) administered every 2 or 3 months.; Other Names: MabThera/Rituxan; Drug: Rituximab; Rituximab subcutaneous injection 375 mg/m^2 administered every 2 or 3 months.; Other Names: MabThera/Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Minimum Observed Plasma Trough Concentration (C trough)	Up to 29 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve From Time Zero to end of Dosing Interval (AUCtau)	Up to 29 months
Maximum Observed Plasma Concentration (Cmax)	Up to 29 months
Time to Reach Maximum Observed Plasma Concentration (Tmax)	Up to 29 months
Plasma Decay Half-Life (t1/2)	Up to 29 months
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	Up to 29 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 16, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimate): June 30, 2009

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

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, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: BP22333; 2008-008490-60