A Pharmacokinetic Study of Subcutaneous and Intravenous MabThera (Rituximab) in Patients With Follicular Lymphoma

• AUC 0-last, Cmax, tmax, t1/2 [ Time Frame: At intervals up to day 84 ] [ Designated as safety issue: No ]
• Adverse events, laboratory parameters [ Time Frame: Throughout study, at each clinic visit ] [ Designated as safety issue: No ]

This 2 stage study will compare the pharmacokinetics and safety profile of subcutaneous and intravenous MabThera (rituximab) in patients with follicular lymphoma.In the first stage, patients who have achieved at least a partial response after induction treatment with iv MabThera will be randomized to one of 3 treatment cohorts, to receive MabThera 375mg/m2 iv, 375mg/m2 sc or 625mg/m2 sc, and pharmacokinetics evaluated on an ongoing basis. Upon selection of the sc dose which results in rituximab C trough values comparable to those achieved with the iv formulation, patients in the second stage of the study will be randomized to receive either the sc or iv 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 sc formulation. The anticipated time on study treatment is up to 31 months for an individual patient, and the target sample size is 215-250 individuals.

• Drug: rituximab [MabThera/Rituxan]
  375mg/m2 iv single dose
• Drug: rituximab [MabThera/Rituxan]
  375mg/m2 sc single dose
• Drug: rituximab [MabThera/Rituxan]
  625mg/m2 sc single dose
• Drug: rituximab [MabThera/Rituxan]
  Optimal dose sc from Part 1

• Active Comparator: Cohort 1 (Part 1)
  Intervention: Drug: rituximab [MabThera/Rituxan]
• Experimental: Cohort 2 (Part 1)
  Intervention: Drug: rituximab [MabThera/Rituxan]
• Experimental: Cohort 3 (Part 1)
  Intervention: Drug: rituximab [MabThera/Rituxan]
• Active Comparator: Cohort 1 (Part 2)
  Intervention: Drug: rituximab [MabThera/Rituxan]
• Experimental: Cohort 2 (Part 2)
  Intervention: Drug: rituximab [MabThera/Rituxan]

Inclusion Criteria:

• adult patients, >=18 years of age;
• CD20-positive follicular non-Hodgkin's lymphoma (NHL);
• partial or complete response a the end of induction treatment with MabThera;
• must have completed induction treatment, and received >= 1 dose of iv MabThera maintenance treatment;
• ECOG performance status of <=2.

Exclusion Criteria:

• histological evidence of transformation of NHL, or types of NHL other han follicular lymphoma;
• presence or history of CNS disease;
• history of malignancy other than follicular NHL which could affect compliance with protocol or interpretation of results;
• recent major surgery (within 4 weeks prior to screening, excluding lymph node biopsy).