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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Lymphoma, Follicular

Intervention / Treatment
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* Drug: Rituximab
* Drug: Rituximab
* Drug: Rituximab
* Drug: Rituximab
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |